Transcript ACTUALITATI IN TERAPIA SCLEROZEI MULTIPLE Caciulata 2007

ACTUALITATI IN TERAPIA
SCLEROZEI MULTIPLE
Caciulata 2007
Dr. Damian Irene
Spitalul Clinic CF Constanta
Tratamentul actual standardizat al SM
(prevazut in ghidurile de practica medicala, in urma validarii eficacitatii
si al profilului lor de siguranta prin studii clinice, conform principiilor
medicinei bazate pe dovezi):
• 1. Tratamente care modifică evoluţia bolii
În prezent, pe plan internaţional sunt acceptate ca fiind medicamente care modifică evoluţia bolii
următoarele:
1.1. Imunomodulatoare:
A. Interferonii beta:
• interferonul beta la (REBIF), cu administrare s.c.
3 doze pe săptămână
• interferonul beta la (AVONEX), cu administrare i.m. 1 doză pe săptămână
• interferonul beta lb (BETAFERON), cu administrare s.c, 1 doză la 2 zile
B. Glatiramerul acetat ( COPAXONE ), cu administrare s.c. câte o doză în fiecare zi
1.2. Imunosupresoare: mitoxantrona (Novantrone)
Alte forme de tratament imunosupresor care pot fi folosite în tratamentul sclerozei multiple
în situaţii particulare nu sunt încadrate şi înregistrate de către autorităţile naţionale şi
internaţionale, în concordanţă cu rezultatele studiilor clinice desfăşurate până în prezent, ca
agenţi care modifică evoluţia bolii.
Tratamentul actual standardizat al SM
• Alte tratamente imunomodulatoare (imunoglobulina G administrate i.v., anticorpii
monoclonali-natalizumab) sau
imunosupresoare (azatioprina, metotrexatul,
ciclofosfamida, cladribina, ciclosporina, etc.) nu au demonstrat cert, până în prezent,
prin studii controlate, eficacitatea în sensul modificării favorabile a evoluţiei SM. De
aceea, ele pot fi folosite în cazuri individuale în care medicul îşi asumă
responsabilitatea indicaţiei, a supravegherii siguranţei şi eficacităţii tratamentului.
• 2. Tratamentul puseului : corticoizi
(scad durata şi severitatea puseului şi numărul de leziuni captante de gadolinium la
examenul IRM cerebral; folosirea lor însă nu diminuează invaliditatea acumulată prin
pusee repetate.)
• Metilprednisolon în doze mari: 1 gr i.v. în 1-2 h zilnic, timp de 3-5 zile. Cele mai
multe protocoale întrerup apoi, brusc, corticoterapia.
• Dexametazona: 8-12 mg i.v. la 8-12 ore timp de 3-7 zile, urmată de administrare
orală
Tratamentul actual standardizat al SM
• 3. Tratamentul simptomatic şi recuperator
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Tratamentul simptomatic şi recuperator are ca scop general ameliorarea calităţii vieţii pacienţilor cu SM, cu
menţinerea integrării lor sociale cât mai mult timp posibil. El este adaptat în funcţie de stadiul clinic al bolii şi de
gradul de invalidare caracteristic fiecărui pacient şi se adresează diferenţiat fiecărui aspect clinic al bolii:
invalidarea motorie, disfuncţia sfincteriană, dificultăţile de comunicare, afectarea cognitivă,
disfuncţiile emoţionale etc
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Obiectivele acestor măsuri sunt: prevenirea complicaţiilor bolii, diminuarea handicapului şi limitarea
dependenţei pacientului prin optimizarea utilizării resurselor fizice şi psihologice restante
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Cele
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tulburările sfincteriene şi de tranzit intestinal
oboseală cronică
spasticitatea şi contracţiile spastice
durerea
disfuncţiile cognitive
depresia
tremorul şi tulburările de echilibru
disfuncţiile sexuale
simptomele paroxistice şi tulburările motorii
mai
frecvente
simptome
asociate
sclerozei
multiple
sunt:
Studii clinice privind etio-patogenia si terapia SM, aflate in
desfasurare la aceasta data: 155 studii
Cele mai semnificative studii aflate in curs de desfasurare la nivel mondial,
in scopul validarii unor noi posibilitati terapeutice in SM:
• 1.RecruitingCombination Therapy in Patients With Relapsing-Remitting
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Multiple Sclerosis (MS)CombiRx
Condition: Relapsing Remitting Multiple Sclerosis
2.RecruitingSafety Study of RTL1000 (Recombinant T Cell Receptor
Ligand) in Subjects With Multiple Sclerosis
Conditions: Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, RelapsingRemitting
3.RecruitingEfficacy and Safety of MBP8298 in Subjects With Secondary
Progressive Multiple Sclerosis
Condition: Multiple Sclerosis, Secondary Progressive
4.RecruitingSafety/Effectiveness of Adding Monthly Dexamethasone to
Weekly Avonex for MS
Conditions: Relapsing-Remitting Multiple Sclerosis,; Mono-Symptomatic Multiple
Sclerosis
8.RecruitingA Randomised Controlled Trial of Neuroprotection With
Lamotrigine in Secondary Progressive Multiple Sclerosis
Condition: Secondary Progressive Multiple Sclerosis
9.RecruitingEvaluation of Efficiency of Ritalin in Multiple Sclerosis (MS)
Patients
Conditions: Relapsing Remitting Multiple Sclerosis; Multiple Sclerosis, Chronic
Progressive
Studii clinice privind etio-patogenia si terapia SM, aflate in
desfasurare la aceasta data
• 10.RecruitingA Safety Study of Combination Treatment With Avonex and
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Placebo-Controlled Dosing of Topamax in Relapsing-Remitting Multiple
Sclerosis
Condition: Multiple Sclerosis
11.Not yet recruitingMesenchymal Stem Cells in Multiple Sclerosis
(MSCIMS)
Condition: Multiple Sclerosis
12.RecruitingEfficacy and Safety of Fingolimod (FTY720) in Patients With
Relapsing-Remitting Multiple Sclerosis
Condition: Multiple Sclerosis
13.RecruitingTrial of Memantine for Cognitive Impairment in Multiple
Sclerosis
Conditions: Multiple Sclerosis; Cognition Disorders
18.RecruitingTCV -01-002: T-Cell Vaccination in the Treatment of Probable
Multiple Sclerosis
Condition: Multiple Sclerosis
19.RecruitingAtorvastatin (Lipitor) Therapy in Patients With Clinically
Isolated Syndrome (CIS) at Risk for Multiple Sclerosis
Condition: Multiple Sclerosis
21.RecruitingStudy of SB-683699 Compared to Placebo in Subjects With
Relapsing-Remitting Multiple Sclerosis (MS)
Condition: Relapsing Remitting Multiple Sclerosis
26.RecruitingBrain Peripheral Benzodiazepine Receptors in Patients With
Multiple Sclerosis
Condition: Multiple Sclerosis
Studii clinice privind etio-patogenia si terapia SM,
aflate in desfasurare la aceasta data
• 27.RecruitingSimvastatin as an Add-on Treatment to Interferon-Beta-1a
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for the Treatment of Relapsing-Remitting Multiple Sclerosis
Condition: Multiple Sclerosis
28.RecruitingCranberry for Prevention of Urinary Tract Infections in
Multiple Sclerosis Patients
Conditions: Multiple Sclerosis; Urinary Tract Infections; Bladder Dysfunction
31.RecruitingUse of Cannabinoids in Patients With Multiple Sclerosis
Condition: Multiple Sclerosis
32.RecruitingEfficacy of 3,4-DAP in Fatigue Associated With Multiple
Sclerosis
Condition: Multiple Sclerosis
33.RecruitingSafety and Efficacy of Cellcept and Avonex as Combination
Treatment in Multiple Sclerosis
Condition: Multiple Sclerosis
34.RecruitingDonor Stem Cell Transplantation for the Treatment of Multiple
Sclerosis
Condition: Multiple Sclerosis
35.RecruitingVisual Impairment, Oscillopsia and Multiple Sclerosis
Condition: Multiple Sclerosis
36.Not yet recruitingTrial of Analgesia With Lidocaine or Extended-Release
Oxycodone for Neuropathic Pain Treatment in Multiple Sclerosis
Conditions: Neuropathic Pain; Chronic Pain; Multiple Sclerosis
Studii clinice privind etio-patogenia si terapia SM,
aflate in desfasurare la aceasta data
• 41.RecruitingPOPART'MUS: Prevention of Post Partum Relapses With
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Progestin and Estradiol in Multiple Sclerosis
Condition: Multiple Sclerosis
42.Not yet recruitingSafety and Efficacy Study of Daclizumab HYP to Treat
Relapsing-Remitting Multiple Sclerosis
Condition: Multiple Sclerosis, Relapsing-Remitting
45.RecruitingStudy of Fampridine-SR Tablets in Multiple Sclerosis Patients
Condition: Multiple Sclerosis
46.RecruitingEfficacy and Safety Evaluation of Nabilone as Adjunctive
Therapy to Gabapentin for the Management of Neuropathic Pain in
Multiple Sclerosis
Conditions: Neuropathic Pain; Multiple Sclerosis
50.RecruitingAspirin for Treatment of Multiple Sclerosis-Related Fatigue
Condition: Multiple Sclerosis
53.RecruitingIPX056 in Subjects With Established Spasticity Resulting
From Multiple Sclerosis
Condition: Multiple Sclerosis
54.RecruitingSafety and Tolerability of Interferon-Beta-1a and
Estroprogestins Association in MS Patients
Condition: Multiple Sclerosis
56.RecruitingNeuropathic Pain Assessment Comparing Pregabalin and
Paroxetine in Management of MS-Induced Neuropathic Pain
Conditions: Neuropathic Pain; Multiple Sclerosis
58.RecruitingNatalizumab Re-Initiation of Dosing
Condition: Multiple Sclerosis, Relapsing-Remitting
Studii clinice privind etio-patogenia si terapia SM,
aflate in desfasurare la aceasta data
• 60.RecruitingFish Oil for the Treatment of Depression in Patients With
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Multiple Sclerosis
Conditions: Multiple Sclerosis; Depression
62.RecruitingStudy of Teriflunomide in Reducing the Frequency of Relapses
and Accumulation of Disability in Patients With Multiple Sclerosis
Condition: Multiple Sclerosis
65.RecruitingEARLY IFNb-1a and Atorvastatin Combination Therapy of
Isolated Clinical Syndrome Suggestive of Multiple Sclerosis
Condition: Multiple Sclerosis
66.RecruitingPilot Study of Teriflunomide as Adjunctive Therapy to
Interferon-β in Subjects With Multiple Sclerosis
Condition: Multiple Sclerosis
67.RecruitingPilot Study of Teriflunomide as Adjunctive Therapy to
Glatiramer Acetate in Subjects With Multiple Sclerosis
Condition: Multiple Sclerosis
70.RecruitingStem Cell Therapy for Patients With Multiple Sclerosis Failing
Interferon A Randomized Study
Condition: Multiple Sclerosis
71.RecruitingHigh-Dose Immunosuppression and Autologous
Transplantation for Multiple Sclerosis (HALT MS) Study
Condition: Multiple Sclerosis
72.RecruitingT-Cell Vaccination in Multiple Sclerosis (MS)
Condition: Multiple Sclerosis
Studii clinice privind etio-patogenia si terapia SM,
aflate in desfasurare la aceasta data
• 77.Not yet recruitingA Study in Multiple Sclerosis Patients to Determine the
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Safety of Different Doses of A4I Compared to Placebo and Their Effects on
Multiple Sclerosis Lesions
Condition: Multiple Sclerosis
81.RecruitingPlacebo Controlled Study in Subjects With Relapsing Forms of
MS to Evaluate the Safety, Tolerability and Effects of CDP323
Condition: Multiple Sclerosis
86.RecruitingMinocycline as Add-on to Interferon-Beta-1a (Rebif®) in
RRMS (Recycline)
Condition: Relapsing-Remitting Multiple Sclerosis94.Not yet recruitingThe Effect
of Levetiracetam (Keppra) on the Treatment of Tremor in Multiple
Sclerosis
Condition: Multiple Sclerosis
97.RecruitingA Randomized Placebo-Controlled, Crossover-Design Study of
the Effects of Low Dose Naltrexone
Condition: Multiple Sclerosis
98.RecruitingPhase II Cladribine Add-on to Rebif New Formulation in MS
Subjects With Active Disease (ONWARD)
Condition: Multiple Sclerosis
99.RecruitingFatigue Treatment Using Provigil
Condition: All Multiple SclerosisPatients
100.RecruitingNeuroprotection With Riluzole Patients With Early Multiple
Sclerosis
Condition: Multiple Sclerosis
Studii clinice privind etio-patogenia si terapia SM,
aflate in desfasurare la aceasta data
• 119.RecruitingEffect of Riluzole as a Symptomatic Approach in Patients
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With Chronic Cerebellar Ataxia
Conditions: Hereditary Ataxia; Multiple Sclerosis; Cerebellar Ataxia
120.Not yet recruitingEvaluation of Natalizumab for thE Relief of MS
Associated FatiGue
Condition: Multiple Sclerosis
127.RecruitingSafety and Tolerability of Rituximab in Neuromyelitis Optica
Condition: Neuromyelitis Optica
133.Not yet recruitingOligodendrocyte Progenitor Cell Culture From Human
Brain
Condition: Demyelinating Diseases
Studii clinice in desfasurare in Romania:
• 37.RecruitingEfficacy and Safety of BG00012 in Relapsing-Remitting
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Multiple Sclerosis
Condition: Relapsing-Remitting Multiple Sclerosis
40.RecruitingEfficacy and Safety Study of BG00012 With Active Reference
in Relapsing-Remitting Multiple Sclerosis
Condition: Relapsing-Remitting Multiple Sclerosis
59.recruitingSafety and Efficacy of Orally Administered Laquinimod for
Treatment of Relapsing Remitting Multiple Sclerosis (RRMS)
Condition: Multiple Sclerosis
Studii clinice in desfasurare in Romania - detalii
Safety and Efficacy of Orally Administered Laquinimod for Treatment of Relapsing Remitting
Multiple Sclerosis (RRMS
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Purpose Determination the efficacy of daily oral treatment with laquinimod 0.6 mg capsules as compared to
placebo in subjects with Relapsing Remitting Multiple Sclerosis (RRMS).
Condition InterventionPhaseMultiple Sclerosis Drug: Laquinimod
Drug: PlaceboPhase IIIPrimary Outcome Measures:
Relapse Rate: Number of confirmed relapses during the double blind study period. [Time Frame: 24 months]
Secondary Outcome Measures:
Accumulation of physical disability measured by the time to confirmed progression of EDSS during the study
period. [Time Frame: 24 months]
MRI Outcomes [Time Frame: 12, 24 months]
Total Enrollment: 1000
Study start: September 2007
ArmsAssigned Interventions1: Experimental Drug: Laquinimod Laquinimod 0.6 mg capsule, oral, once
daily 2: Placebo Comparator Drug: Placebo Multinational, multicenter, randomized, double-blind, parallel-group,
placebo-controlled study, to evaluate the efficacy, tolerability and safety of daily oral administration of laquinimod
0.6mg in RRMS subjects. Eligible subjects will be equally randomized into one of the following treatment and
placebo study groups. Subjects will be regularly evaluated at study sites including physical and neurological
medical evaluation, clinical laboratory testing and medical imaging evaluation.
Eligibility
Ages Eligible for Study: 18 Years - 55 Years, Genders Eligible for Study: Both
Criteria
Inclusion Criteria:
Between 18 and 55 years of age
Confirmed MS diagnosis with a relapsing-remitting disease course as defined by the Revised McDonald criteria
Ambulatory with converted Kurtzke EDSS score of 0-5.5.
Exclusion Criteria:
MS diagnosis including progressive forms of MS
Women who are pregnant or breastfeeding
Studii clinice in desfasurare in Romania - detalii
Efficacy and Safety of BG00012 in Relapsing-Remitting Multiple Sclerosis
Purpose : To determine if treatment with BG00012 can decrease the number of MS relapses during a certain time
period. To determine if, over time, BG00012 treatment can decrease the number of certain types of brain lesions
commonly seen in MS patients and slow down the time it takes for the disease to get worse.
• The purpose of this study is also to determine the safety of BG00012 and how well it is tolerated. Another goal is
to see what effect BG00012 may have on tests and evaluations used to assess MS.
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Primary Outcome Measures:
To determine if BG00012 is effective in reducing the proportion of relapsing subjects at 2 years.
Secondary Outcome Measures:
There are multiple secondary outcomes.
Total Enrollment: 1011
Study start: January 2007
Eligibility
Ages Eligible for Study: 18 Years - 55 Years, Genders Eligible for Study: Both
Inclusion Criteria:
Unless otherwise specified, to be eligible to participate in this study, candidates must meet the following eligibility
criteria at the time of the randomization:
Aged 18 to 55 years old, inclusive, at the time of informed consent.
Must have a confirmed diagnosis of RRMS according to McDonald criteria #1-4.
Must have a baseline EDSS between 0.0 and 5.0, inclusive.
Must have relapsing-remitting disease course.
Exclusion Criteria:
Unless otherwise specified, candidates will be excluded from study entry if any of the following exclusion criteria
exist at randomization:
Other chronic disease of the immune system, malignancies, acute urologic, pulmonary, gastrointestinal disease.
Pregnant or nursing women.
Noi posibilitati terapeutice in SM:
- Terapia cu celule stem
- Vaccinuri
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premise etio-patogenice
principiile metodelor
stadiul rezultatelor actuale
studii clinice in desfasurare (detalii)
Noi posibilitati terapeutice in SM:
Terapia cu celule stem
studii clinice in desfasurare (detalii)
Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS)
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Sponsors and Collaborators:University of Cambridge Cambridge University Hospitals NHS Foundation
Trust.Medical Research Council
Purpose Hypothesis: Intravenous administration of bone marrow-derived autologous adult human mesenchymal
stem cells is a safe novel therapeutic approach for patients with multiple sclerosis
Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) is a phase I/IIA trial designed to establish the safety of
intravenous administration of bone marrow-derived autologous adult human mesenchymal stem cells to patients
with multiple sclerosis.
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Historical Control, Crossover Assignment,
Safety/Efficacy Study
Official Title: Autologous Adult Human Mesenchymal Stem Cells: a Neuroprotective Therapy for Multiple Sclerosis
Further study details as provided by University of Cambridge:
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Primary Outcome Measures:
Adverse events
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Secondary Outcome Measures:
Visual function (acuity and colour)
Visual evoked potential latency
Optic nerve Magnetisation Transfer Ratio
Retinal nerve fibre layer thickness (by optical coherence tomography)
Brain lesion Magnetisation Transfer Ratio
MRI brain T1 hypointensity load
T cell response suppression
Multiple Sclerosis Functional Composite Score
Expanded Kurtzke Disability Status Score
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Noi posibilitati terapeutice in SM:
Terapia cu celule stem
studii clinice in desfasurare (detalii)
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Total Enrollment: 20
Disease under investigation: Multiple Sclerosis
Phase: I/IIA
Number of patients: 20
Design: 1 year cross over, single treatment at 6
months
Intervention: Administration of bone marrowderived autologous mesenchymal stem cells
Route of administration: Intravenous
Dose: 2,000,000 Mesenchymal Stem Cells per
kilogram
Source of patients: Referrals accepted from
Neurologists in East Anglia and North London, UK
Referral Criteria: (all 4 required)
Clinically definite multiple sclerosis
Disease duration 2 - 15 years
Expanded Kurtzke Disability Status Score 2.0 - 5.5
(inclusive)
Evidence of optic nerve damage by
– history of optic neuritis, or
– relative afferent pupillary defect, or
– optic atrophy on fundoscopy, or
– abnormal visual evoked potential from either
or both eyes suggestive of demyelination
Eligibility Ages Eligible for Study: 18 Years 50 Years, Genders Eligible for Study: Both
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Inclusion Criteria:
Clinically definite multiple sclerosis
Disease duration 2 - 15 years
Expanded Kurtzke Disability Status Score 2.0 - 5.5
Evidence of optic nerve damage by:
history of optic neuritis, or
relative afferent pupillary defect, or
optic atrophy on fundoscopy, or
abnormal visual evoked potential from either or
both eyes suggestive of demyelination
Prolonged visual evoked potential P100 latency with
preserved waveform
T2 lesion on MRI optic nerve
<40% loss of retinal nerve fibre layer thickness on
optical coherence tomography
Exclusion Criteria:
Age < 18 years
Age > 50 years
Patient lacks capacity to give informed consent
Presence of a severe bleeding disorder
Planning a pregnancy during the trial period
Current MS disease modifying therapy
Location and Contact Information
Please refer to this study by ClinicalTrials.gov
identifier NCT00395200
Siddharthan Chandran, MBChB, PhD
+44 (0)
1223 331160 [email protected]
Noi posibilitati terapeutice in SM:
Terapia cu celule stem
studii clinice in desfasurare (detalii)
Donor Stem Cell Transplantation for
the Treatment of Multiple
Sclerosis
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Purpose
While the cause of MS in not known, there is an
autoimmune component that destroys nerve cells.
Autoimmunity is a condition where an individual's
immune system attacks his/her own cells. Bone
marrow stem cell transplantation has been shown to
halt autoimmunity. Stem cell transplant can be
performed using the patient’s own cells, or donor
cells. The general consensus in the field is that
donor transplant is most likely to halt disease
progression. This study is designed to evaluate the
safety of a donor transplant procedure as a therapy
for relapsing remitting multiple sclerosis (RRMS).
Two factors limit the widespread application of
traditional donor stem cell transplant: 1) preparing
the patient for transplant (conditioning); and 2) graftversus-host disease (GVHD). Traditional
conditioning destroys the recipient's immune system
and requires that the marrow transplant be
successful because the patient is unable to fight off
infection if the donor cells do not survive. GVHD
occurs when donor immune cells recognize the
recipient’s cells as foreign tissue and attack them.
Severe GVHD can result in death.
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This study utilizes a new approach to conditioning
which leaves the patient's immune system intact.
The transplant product is depleted of GVHDproducing cells but retains tolerance-promoting
cells, called facilitating cells, which are intended to
ensure the donor and recipient cells coexists
peacefully. The toxicity of conditioning and
transplantation is significantly reduced. The end
result is a marrow system that contains recipient
and donor cells, a state called mixed chimerism.
In this study, we will determine the appropriate cell
dose to safely establish mixed chimerism following
partial conditioning in patients with RRMS. The
study takes a gradual approach to increasing the
cell dose to achieve mixed chimerism. Each patient
will receive a cell dose one unit above the dose
received by the most recent safely transplanted
patient. We believe this study will provide a
breakthrough in the treatment of MS. The goal of
this proposal is to evaluate the potential of safely
establishing mixed chimerism to interrupt the
autoimmune process and end the devastating
effects of MS.
Primary Outcome Measures:
Stem cell engraftment/chimerism
Secondary Outcome Measures:
Disease remission
Total Enrollment: 15
Noi posibilitati terapeutice in SM:
Terapia cu celule stem
studii clinice in desfasurare (detalii)
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Eligibility
Ages Eligible for Study: 18 Years - 55
Years, Genders Eligible for Study: Both
Inclusion Criteria:
Clinically definite MS according to the McDonald
criteria
Confirmed diagnosis of relapsing-remitting MS.
Age between 18 and 55 years
Extended Disability Status Score (EDSS) between 0
and 5.0
Relapse within the last year or sustained disability
progression of 1.0 for six months
Treatment with high dose, high frequency
Interferon-β therapy, or failure to tolerate
Interferon-β therapy
DLCO> 50% (unless cleared by physician)
EF > 40% (unless cleared by cardiologist)
Required initial laboratory data (obtained within 30
days prior to transplant, unless otherwise specified)
– HIV-1,2 antigen and antibody negative
– HBsAg negative (chronic hepatitis B carriers
without clinical evidence of liver disease can
be considered on an individual basis if it is
determined that the added risk is justified by
the prognosis and lack of treatment
alternatives)
– Hepatitis C antibody negative (positive
antibody allowed if antigen (RNA)-negative
and no clinical evidence of cirrhosis)
– CMV, hepatitis B, HTLV-1,2, EBV, and Herpes
antibody status known
– Pregnancy test negative
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No life-threatening organ dysfunction.
– Uncontrolled or severe cardiovascular disease,
including recent (<6 months) myocardial
infarction, angina (symptomatic despite
optimal medical management), lifethreatening arrhythmia or hypertension
Able to give informed consent
Exclusion Criteria:
Women who are of child bearing potential must
have a negative pregnancy test (serum pregnancy
test [HCG]) within 48 hours of initiating total body
irradiation and agree to use reliable contraception
for 1 year following transplant.
Concomitant severe diseases (respiratory, renal,
liver, cardiac failures, psychiatric disorders,
neoplasms)
Recurrent urinary, pulmonary infections.
Active bacterial, viral, or fungal infection
Active peptic ulcer disease
Previous treatments with total lymphoid irradiation
or total body irradiation
Interferon-neutralizing antibody positive with a titer
greater than 20
Relapse in the month preceding enrollment
Poor compliance
Location and Contact Information
United States, Kentucky
Institute for Cellular Therapeutics, University of
Louisville, Louisville, Kentucky, 40202, United
States;
Noi posibilitati terapeutice in SM:
Terapia cu celule stem
studii clinice in desfasurare (detalii)
• Stem Cell Therapy for Patients
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With Multiple Sclerosis Failing
Interferon A Randomized Study
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Total Enrollment: 110
Study start: January 2006
To assess the efficacy of autologous PBSCT versus FDA
approved standard of care ( i.e. interferon, copaxone, or
mitoxantrone) for inflammatory multiple sclerosis failing
interferon therapy. The endpoints to be considered in this
study are:
Eligibility
Ages Eligible for Study: 18 Years - 55 Years, Genders
Eligible for Study: Both
Criteria
Inclusion Criteria:
Age between 18-55, inclusive.
Diagnosis of MS using Poser criteria of “clinically definite” MS
(Appendix A).
An EDSS of 2.0 to 6.0 (Appendix B).
Inflammatory disease despite primary disease modifying
therapy with at least 4 months of interferon. Inflammatory
disease is defined by either MRI showing gadolinium
enhancing lesions or clinically as acute relapses treated with
IV solumedrol. Failure is defined as two or more clinical
relapses with documented neurologic changes within the year
prior to the study. (NOTE: Relapses must have required
treatment with corticosteroids). Failure may also be defined as
one relapse within the year prior to study if there is evidence
on MRI of active inflammation (i.e., gadolinium
enhancement).
Exclusion criteria
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Inability or unwillingness to pursue effective means of birth
control. Effective birth control is defined as 1) refraining from
all acts of vaginal intercourse (ABSTINENCE); 2) consistent
use of birth control pills; 3) injectable birth control methods
(Depo-provera, Norplant); 4) tubal sterilization or male
partner who has undergone vasectomy; 5) placement of an
IUD (intrauterine device); or 6) use, with every act of
intercourse, of diaphragm with contraceptive jelly and/or
condoms with contraceptive foam.
Failure to willingly accept or comprehend irreversible sterility
as a side effect of therapy.
FEV1/FVC < 60% of predicted after bronchodilator therapy (if
necessary).
DLCO < 50% of predicted.
Resting LVEF < 50 %.
Bilirubin > 2.0 mg/dl.
Serum creatinine > 2.0 mg/dl.
Known hypersensitivity to mouse, rabbit, or E. Coli derived
proteins, or to iron compounds/medications.
Presence of metallic objects implanted in the body that would
preclude the ability of the patient to safely have MRI exams.
Diagnosis of primary progressive MS.
Platelet count < 100,000/ul, WBC < 1,500 cells/mm3.
Psychiatric illness, mental deficiency or cognitive dysfunction
making compliance with treatment or informed consent
impossible.
Active infection except asymptomatic bacteruria.
Location and Contact Information
Please refer to this study by ClinicalTrials.gov
identifier NCT00273364
United States, Illinois
Northwestern University, Feinberg School of
Medicine, Chicago, Illinois, 60611, United States; Recruiting
Dzemila Spahovic, MD 312-908-0059 [email protected]
Richard Burt, MD, Principal Investigator
Noi posibilitati terapeutice in SM:
Terapia cu celule stem
studii clinice in desfasurare (detalii)
High-Dose Immunosuppression and Autologous Transplantation for Multiple
Sclerosis (HALT MS) Study
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Purpose
The purpose of this study is to determine the effectiveness of a
new treatment for multiple sclerosis (MS), a serious disease in
which the immune system attacks the brain and spinal cord. MS
can be progressive and severe and lead to significant disability.
The study treatment involves the use of high-dose
chemotherapeutic drugs to suppress the immune system. The
participant’s own (autologous) blood-forming (hematopoietic,
CD34+) stem cells are collected before the chemotherapy is
given, and then transplanted back into the body following
treatment. Transplantation of autologous hematopoietic stem
cells is required to prevent very prolonged periods of low blood
cell counts after the high-dose chemotherapy.
Phase II
Total Enrollment: 30
Eligibility Ages Eligible for Study: 18 Years - 60
Years, Genders Eligible for Study: Both
Inclusion Criteria:
Diagnosis of relapsing-remitting or progressive-relapsing
multiple sclerosis for less than 10 years using McDonald Criteria.
More information on this criterion can be found in the protocol.
Score between 3.0 and 5.5 on the Expanded Disability Status
Scale (EDSS)
T2 abnormalities on brain MRI consistent with MS
Two or more relapses in 12 months time on interferon (IFN),
glatiramer acetate (GA), or mitoxantrone with EDSS increase
greater than 0.5, maintained for greater than 3 months OR one
relapse on IFN, GA, or mitoxantrone, together with MRI
changes consistent with poor prognosis. On IFN or GA for at
least 6 months before the relapses occur that are counted to
satisfy previous inclusion criterion OR have received at least 3
doses of mitoxantrone on a treatment schedule before the
relapses occur that are counted to satisfy previous inclusion
criterion
Approval by an MS Review Panel to participate in the study.
More information on this criterion can be found in the protocol.
In good clinical condition with adequate organ function and
without coexisting medical problems that would increase the
risk to the participant
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Willing to use acceptable methods of contraception
Willing and able to comply with all study requirements
Willing to accept and comprehend irreversible sterility as side effect of therapy
Exclusion Criteria:
Primary progressive MS
Secondary progressive MS without relapses (i.e., progression without
exacerbations or relapses) for 12 or more months
Neuromyelitis optica, a disease similar to MS
Initiation of new immunosuppressant treatment after the participant becomes
eligible for the protocol or continuance of immunosuppressant drugs after the
participant is screened for the protocol. Treatment with IFN, GA, or
corticosteroids is permitted after the participant becomes eligible for the
protocol.
Lapse of greater than 4 months between the time a participant is eligible for
the protocol and initiation of protocol treatment except when judged
acceptable by the MS Review Panel
Prior treatment with investigational immunosuppressive agents within 3
months of study eligibility
Prior treatment with natalizumab
History of cytopenia consistent with the diagnosis of myelodysplastic
syndrome (MDS)
Active hepatitis B or C infection, cirrhosis, or HIV infection
Uncontrolled diabetes mellitus
Uncontrolled viral, fungal, or bacterial infection. Patients with asymptomatic
bacteriuria are not excluded.
Any illness that would jeopardize the ability to tolerate aggressive
chemotherapy
Prior history of malignancy, except localized basal cell or squamous skin
cancer. Other malignancies for which the subject is judged cured by the
administered therapy will be considered on an individual basis.
Hypersensitivity to mouse, rabbit, or Escherichia coli-derived proteins or to
iron compounds/medications
Metallic objects implanted in the body that would affect MRI exams
Psychiatric illness, mental deficiency, or cognitive dysfunction
Pregnancy
Noi posibilitati terapeutice in SM:
Terapia cu celule stem
studii clinice in desfasurare (detalii)
Oligodendrocyte Progenitor Cell Culture From Human Brain
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Purpose Recent developments in the understanding of stem- and progenitor cell differentiation
raises hopes that brain damage in chronic neurological diseases may become repaired by
systemic or focal transplantation of such cells. Clinical trials of stem- or progenitor cell
transplantation in multiple sclerosis are currently premature. The researchers developed a
protocol for human oligodendrocyte progenitor cell culture from human brain for the treatment of
demyelinating disease.
Phase I
Primary Outcome Measures:
Number of oligodendrocyte progenitor cell differentiation
Total Enrollment: 100
Expected completion: March 2008
Eligibility
Ages Eligible for Study: 20 Years - 65 Years, Genders Eligible for Study: Both
Criteria
Inclusion Criteria:
Male or female 20-65 years of age
Informed consent
Has elective craniotomy surgery
Exclusion Criteria:
HIV, hepatitis, and other central nervous system (CNS) infections
Dementia, Alzheimer disease, and neurodegenerative disease
Noi posibilitati terapeutice in SM:
Vaccinuri
studii clinice in desfasurare (detalii)
TCV -01-002: T-Cell Vaccination in the Treatment of Probable
Multiple Sclerosis
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Purpose
In the present study, we, the investigators at Sheba Medical Center, intend to evaluate T cell vaccination (TCV) in
patients with probable multiple sclerosis (MS) within up to 3 months after the first clinical attack. It is of the
utmost importance to evaluate the treatment effects at the onset of disease, i.e. in patients with probable MS, in
order to evaluate whether early treatment can prevent the second attack (conversion to definite MS). Moreover,
at disease onset, the immunological process of epitope spreading associated with the exposure of the immune
system to myelin antigens is still limited. With additional attacks, increased recognition of new self-determinants
of encephalitogenic peptides presented to the immune system during the inflammatory process occurs, and
enhances further disease activity. The aim of the early TCV treatment approach is to stop this process as early as
possible, during the onset of the disease, thus preventing additional attacks and disease progression.
We will evaluate the effect of TCV on clinical, immunological and magnetic resonance imaging (MRI) parameters
in patients with probable MS.
Phase III Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study
Primary Outcome Measures:
The rate of progression to definite MS (second attack) during the study
Time to progression to definite MS (second attack)
Secondary Outcome Measures:
Change in the count of new gadolinium (GD) enhancing lesions from two baseline (B) MRIs to the final (F) MRIs
Change in total volume of new GD enhancing lesions from two baseline MRIs (B) to the final MRIs (F)
The change in neurological disability as measured by the Expanded Disability Status Scale (EDSS)
Noi posibilitati terapeutice in SM:
Vaccinuri
studii clinice in desfasurare (detalii)
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Total Enrollment: 80
Inclusion criteria:
Age: 15 - 50 years.
Three months within the acute onset of neurological symptoms suggestive of the first attack of
multiple sclerosis.
Diagnosis of CPMS C3 (Poser criteria).
Positive brain MRI according to Fazekas criteria.
Negative pregnancy test and use of effective contraceptive for female patients who are sexually
active.
Signed written informed consent.
Exclusion criteria:
Blood tests suggestive of other autoimmune diseases.
Known allergic reactions to MRI contrast media.
A clear regression of the neurological symptoms after the first attack that suggests a primaryprogressive course.
Corticosteroid treatment in the previous 4 weeks (28 days).
Previous treatment with immunosuppressive medications such as cyclophosphamide,
azathioprine, methotrexate, mitoxantrone or cyclosporine.
Previous treatment with interferon beta 1a or 1b, copolymer-1, IVIg, plasmapheresis.
Location and Contact Information
Sheba Medical Center, Ramat Gan, 52621, Israel;
Noi posibilitati terapeutice in SM:
Vaccinuri
studii clinice in desfasurare (detalii)
T-Cell Vaccination in Multiple
Sclerosis (MS)
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Purpose
The purpose of this study is to evaluate the
safety of T-cell vaccination in MS patients.
Immunization of MS patients with irradiated
autologous encephalitogenic myelin peptides
(EMP) specific T-cell lines or clones.
Clinical immunologic and neuroradiologic
evaluation.
Primary Outcome Measures:
safety assessment of T-cell vaccination in
nonresponding MS patients
Phase I
Phase II
Total Enrollment: 20
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Eligibility
Ages Eligible for Study: 16 Years - 60
Years, Genders Eligible for Study: Both
Criteria
Inclusion Criteria:
Definite MS (post criteria)
Relapsing remitting or primary progressive
clinical course. At least one relapse in the
last two years.
Disease duration > 1 year
Expanded Disability Status Scale (EDSS)
between 0-6
Brain magnetic resonance imaging (MRI)
compatible with MS
Not involved in any other clinical trials
No other systemic disease
Exclusion Criteria:
Does not comply with the above
Location and Contact Information
Multiple Sclerosis Center, Ramat
Gan, Israel;
Noi posibilitati terapeutice in SM: Vaccinuri
Induction of Antigen-Specific Tolerance in Multiple Sclerosis After
Immunization With DNA Encoding Myelin Basic Protein in a Randomized,
Placebo-Controlled Phase 1/2 Trial
Amit Bar-Or, MD; Timothy Vollmer, MD; Jack Antel, MD; Douglas L. Arnold, MD; Caroline Anita
Arch Neurol. 2007;
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Objective To assess safety and immune modulation by BHT-3009, a tolerizing DNA vaccine
encoding full-length human myelin basic protein, in patients with multiple sclerosis (MS).
Design The study was a randomized, double-blind, placebo-controlled trial. Subjects receiving
placebo were crossed over into an active arm after treatment unblinding.
Setting The trial was conducted at 4 academic institutions within North America.
Patients Thirty patients with relapsing-remitting or secondary progressive MS who were not
taking any other disease-modifying drugs were enrolled in the trial. Further, the patients were
required to have either 1 to 5 gadolinium-enhancing lesions on screening brain magnetic
resonance imaging (MRI), a relapse in the previous 2 years, or disease worsening in the previous
2 years.
Interventions BHT-3009 was administered as intramuscular injections at weeks 1, 3, 5, and 9
after randomization into the trial, with or without 80 mg of daily oral atorvastatin calcium in
combination. Three dose levels of BHT-3009 were tested (0.5 mg, 1.5 mg, and 3 mg).
Main Outcome Measures The primary outcome measures were safety and tolerability of BHT3009. Secondary outcome measures included the number and volume of gadolinium-enhanced
lesions on MRI, relapses, and analysis of antigen-specific immune responses.
Results BHT-3009 was safe and well tolerated, provided favorable trends on brain MRI, and
produced beneficial antigen-specific immune changes. These immune changes consisted of a
marked decrease in proliferation of interferon-–producing, myelin-reactive CD4+ T cells from
peripheral blood and a reduction in titers of myelin-specific autoantibodies from cerebral spinal
fluid as assessed by protein microarrays. We did not observe a substantial benefit of the
atorvastatin combination compared with BHT-3009 alone.
Conclusion In patients with MS, BHT-3009 is safe and induces antigen-specific immune
tolerance with concordant reduction of inflammatory lesions on brain MRI.
Noi posibilitati terapeutice in SM: Vaccinuri
Induction of Antigen-Specific Tolerance in Multiple Sclerosis After
Immunization With DNA Encoding Myelin Basic Protein in a Randomized,
Placebo-Controlled Phase 1/2 Trial
CONCLUZII
• Terapia SM este in continua dezvoltare, paralel cu evolutia intelegerii
mecanismelor etio-patogenice ale bolii;
• O terapie corecta si completa este necesara pentru asigurarea
calitatii vietii si a prognosticului vital si dizabilitant