Transcript Evidence - Calmare Pain Relief Solutions

Calmare® Device: latest scientific
evidence & demonstration
Banner MD Anderson Cancer Center
Scientific Presentation, May 9, 2014
Rebecca Armendariz, MD
Disclosures
• Nothing to disclose
• Introductions
– Competitive
Technologies, Inc.
Objectives
• Background of the technology
• Latest Evidence
• Who is using it?
• Should we use it?
• Demonstration
Background
• World Health Organization (WHO) projects >
15 million new cancer cases by 20201
• > 60% Pain prevalence in metastatic,
advanced or terminal phases of cancer,
~ 30% in survivors2
• Cancer pain not adequately treated in a
significant percentage of patients, ranging
from 56 to 82.3% 3,4
• Most advanced cancer patients have at least
two types of cancer-related pain
• Incidence of Chemotherapy Induced
Peripheral Neuropathy (CIPN) is widely
variable
Background
Calmare® Scrambler Therapy MC-5A
Transcutaneous electrical stimulator device for
chronic neuropathic pain.
Background
• Calmare® Scrambler Therapy MC5A
• Developed at University of Rome,
Italy by Professor Giuseppe
Marineo, D.Sc, M.S.
• Distributed world wide by
Competitive Technologies Inc,
Fairfield, CT
• Manufactured by GEOMC Co.,
Ltd in Seoul, Korea
Background
• FDA cleared in Feb 2009 based on devices ES-160 and
Neuro Wave 6 (TENS units)
– Physician Procedure Code 0278T, Transcutaneous electrical
modulation pain reprocessing with placement of electrodes
– ICD-9 Codes: 338.3 - Neoplasm-related pain, 355.9 Mononeuritis of unspecified site & 357.7 - Polyneuropathy
• CE Mark Certification 2008
• Non-invasive transcutaneous nerve stimulation technology
for chronic neuropathic pain refractory to medications
Background
TENS
• Uses linear standard impulses
with on-off biphasic current to
excite A-Beta fibers
• High Frequency > 50 Hz with low
Intensity below motor
contraction
• Or low frequency < 10 Hz with
intensity that produces motor
contraction
CALMARE
• Uses a proprietary algorithm to
assemble strings of patterns that
create a “non-pain” signal
(artificial neuron)
• Creates 16 different synthetic
action potentials similar to
endogenous waveforms
• Translated into 4 different phases
creating variable nonlinear
waveforms that stimulate C and ADelta fibers (width > 5 msec)
Background
TENS
CALMARE
• Continuous pulse pattern, square
wave
• Charge per phase is 38.8
microcoulombs
• Pulse width of 200 microsecs &
pulse freq of 80 Hz
• Phase duration is 6.8 - 10.9
microsecs with pulse rate of 43-52
Hz
• Increased until pt feels sensation
• Frequency never exceeds 52 Hz
• Gate-Control Theory
– Melzack & Wall, 1965
• Mean energy delivered per sec <
TENS device
Background
A-Beta Fiber
A-Delta Fiber
• A-Class thinly myelinated afferent
fiber
• A-Class thinly myelinated afferent
fiber
• Muscle spindle secondary
endings (muscle length)
• Sensory afferent fiber
• Touch & kinesthesia
• Cold, pressure and acute sharp
pain
C-Fiber
• C-Class non-myelinated afferent
fiber
• Thermal, mechanical & chemical
sensory fiber
Background
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Background
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Background
Substantia
Gelatinosa
Nucleus
Proprius
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decompressor
are needed to see this picture.
Background
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Background
Background
Perception = Transmission - Modulation
What is it used for?
• Chronic neuropathic pain
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Peripheral Neuropathy
Post-Herpetic Neuralgia
CRPS / RSD
Carpal Tunnel Syndrome
Phantom limb pain
Chronic back pain
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Pudendal Pain
Failed Back Surgery Synd
Fibromyalgia
Post-Surgical pain
Perineal Pain
Sciatica
• Oncologic pain
– Chemo Induced Periph Neuropathy
– Radiation Plexopathy
– Pain from bone mets
– Drug-resistant pain
Contraindications?
• Patients with metal implants such as pacemakers, automatic
defibrillators, aneurysm clips, vena cava clips and skull plates,
have a seizure disorder or or pregnant.
• Patients with undiagnosed pain.
• Electrodes should not be placed on the carotid sinus, head, A/P
thorax or over the heart.
• Can be used on patients with metal implants such as total knee,
hip, shoulder and other joint replacements as well as on patients
with implanted pins, clips, screws, plates and cages used for
orthopedic repair.
Adverse Side Effects
• No significant side effects
– Non-invasive, non-addictive, alternative to drug therapy
• Outcomes:
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Significant pain reduction and/or relief
Reduction/elimination of medication use
Less pharmacological adverse side effects
Improved functionality
Improved quality of life
Evidence
Evidence
• Marineo, G. - 2003 first published trial involving 11 patients with
cancer with resistant visceral pain5
– Pain reduced from 8.6 out of 10 before the first treatment to 2.3 out of
10 after the first treatment and to less than 0.5 out of 10 at the end of
10 sessions (P < 0.0001 by paired t-test)
– 9 of the 11 pts stopped pain meds within 5 sessions (until death)
– No toxicities or adverse side effects
• Sabato, A.F. & Marineo, G - 2005 trial with 226 patients with
neuropathic pain6
– Reported 80% of pts had > 50% pain relief, 10% responded with pain
relief from 25% to 49%, and 10% had no response (P < 0.0001 by
paired t-test)
– No toxicities or adverse side effects
• FDA clearance based on these studies
Evidence
• Smith, T.J. et al - 2010 - Pilot trial of a Patient-Specific Cutaneous
Electrostimulation Device (MC5-A Calmare®) for CIPN7
– 18 patients given 10 days of treatment, 16 completed
– Mean age 58.6 years, 4 men, 14 women
– CIPN range 3 months - 8 years
– Predominant study agents taxane and bortezomib
– Primary Objective: reduce CIPN pain by 20% based on threshold used
in the Cancer Pain Trial12
– Repeated-measures random-effects analysis of variance for adjusted
pain score
– Daily pain score variability
Evidence
• Smith, T.J. et al - 2010 Pilot trial for treatment of CIPN7
– Pain score (NRS) fell 59% from 5.81 + 1.11 before treatment to 2.38 +
1.82 at the end of 10 days (P < 0.0001 by paired t-test)
– Strong statistically significant difference between the pre and post-daily
pain scores (P < 0.001)
Evidence
• Smith, T. et al - 2010 Pilot trial for treatment of CIPN7
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No toxicity was seen
Some responses were durable
Improved sensation, gait and motor function
Return to ‘normal’ sensation & partial relief of numbness
Evidence
• Smith, T. et al - 2010 Pilot trial for treatment of CIPN7
– Four patients had their CIPN reduced to zero
– Only two had complete resolution without maintenance
Secondary Endpoint measures showed:
– No change in morphine oral equivalent dose (3 decreased)
– No other formal QOL or symptom, other than pain, changed significantly
Evidence
• Ricci, M., et al. 2012 Managing Chronic Pain: results from an openlabel study sing MC5-A Calmare® device8
– 73 pts: 40 with cancer & 33 without cancer
– Median age 66 yrs (28 - 87 range), 38 male, 35 female
– Pain present > 3 months in 81% of patients (75% continuous)
– Assess efficacy and tolerability of the device
– NRS assessed weekly during Tx and weekly for 2 week follow-up
Evidence
• Ricci, M., et al. 2012 Managing Chronic Pain8
Evidence
• Ricci, M., et al. 2012 Managing Chronic Pain8
Evidence
• Ricci, M., et al. 2012 Managing Chronic Pain8
Evidence
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Ricci, M., et al. 2012 Managing Chronic Pain8
Evidence
• Marineo, G, Smith, T. et al - 2012 - Scrambler Therapy May Relieve
Chronic Neuropathic Pain More Effectively Than Guideline-Based
Drug Management: Results of a Pilot, RCT9
– 52 pts randomized to either 10 day Calmare Tx vs pharm
– Pain matched (post surg neuropathic pain, PHN, spinal stenosis)
– VAS pain scores at 1, 2, 3 months, med use, allodynia
– Control group (Pharm) managed based on European Federation of
Neurological Societies (EFNS) Clinical Practice Guidelines
– Most common baseline therapy: Amitryptyline, Gabapentin & Tramadol > switched to Amitriptyline, Clonazepam and Oxycodone
Evidence
• Marineo, G, Smith, T. et al - 2012 Pilot RCT Calmare vs Drugs9
– Results: 1 Mos = VAS reduced 28% in control and 91% in Scrambler
(P<0.0001)
Evidence
Evidence
Evidence
• Marineo, G, Smith, T. et al - 2012 Pilot RCT Calmare vs Drugs9
– Opioids eliminated in 11 of 17 cases, halved in 1 case, 5 unvaried
– Anticonvulsants eliminated in 17 of 24 cases, reduced in 1 case, 6
unvaried
– Antidepressants eliminated in 9 of 19 cases, reduced in 4 cases, 6
unvaried
– Overall drug consumption reduced by 72% in Calmare group
Evidence
• Marineo, G, Smith, T. et al - 2012 Pilot RCT Calmare vs Drugs9
– Allodynia was reduced in Calmare group from 77% to 15%
– Clinically significant
Evidence
Figure 4. Effect of Therapy by Mono-or Polyneuropathy
Evidence
• Pachman, D.R., et al. 2012 ASCO Abstract - Pilot study for
treatment of chemotherapy induced peripheral neuropathy.10
– 11 pts, mean age 57, 3 men 8 women
– majority symptoms > 2 years, various agents
– Daily NRS, 10 Txs of 30 mins each
Evidence
• Smith, T.J., et al. 2012 ASCO Abstract - Treatment of post-herpetic
pain with scrambler therapy, a patient-specific neuro-cutaneous
electrical stimulation device.11
– 10 pts mean age 54 + 13 yrs, 6 men 4 women
– Mean PHN duration 15.6 months (2.5 - 48 months range)
– NRS at 1, 2, & 3 months
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Results:
Baseline pain score 7.64 + 1.46 diminished to 0.42 + 0.89 at one month
(1.93 at 2 months and 2.21 at 3 months)
Achieved maximum pain relief with < 5 treatments
Continued relief at 2 and 3 months
5 out of 10 pts had continued complete disappearance of pain
Most patients were able to stop or reduce pain medications
Evidence
• Sparadeo, F. et al. 2012 - Scrambler Therapy: An Innovative and
Effective Treatment for Chronic Neuropathic Pain12
– 173 pts treated for 10 days with Calmare® device
– Follow-up analysis on 91 patients
– VAS before and after each treatment
– VAS & Brief Pain Inventory at baseline and again 3 to 6 months post
treatment
– Single site spine pain, neuralgia, CRPS, multi-site pain patients
Evidence
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Results: Mean VAS score before starting treatment was just over 7.24 and
diminished to 3 after the 10th session.
VAS Scores before and after Calmare
Evidence
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Results: BPI score means by diagnosis showed statistically significant
improvement across all four groups after 10 treatments (p< .01) paired t-tests.
Evidence
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Results: Mean scores in all variables of the BPI were diminished after
Calmare tx (P<.0001) and dropped by over 50%.
Evidence
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Results: Analysis of Variance results with means comparisons on all
dependent variables (BPI & VAS) within the four diagnostic groups.
Evidence
Evidence
Evidence
Who Is Using Calmare?
• Dept of Defense has 14 machines
• Andrews Air Force Base is using
Calmare®
• Navy base in San Diego (Balboa) has
integrative Medicine Clinic and is
offering Calmare®
• Walter Reed is utilizing Calmare® for
undisclosed Pain syndromes
Who Is Using Calmare?
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Naval Medical Center Portsmouth
Portsmouth, VA 23708-2111
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Naval Hospital Bremerton
Bremerton, WA 98312-1898
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Naval Medical Center San Diego
San Diego, CA 92134-5000
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Naval Hospital Jacksonville
Jacksonville, FL 32214-5000
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Naval Medical Center Bethesda
Bethesda, MD 20889
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Naval Hospital Camp Pendleton
Camp Pendleton, CA 92055-5008
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Naval Hospital Camp Lejeune
Camp Lejeune, NC 28547-0100
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U.S. Naval Hospital Okinawa
Chatan-cho, Okinawa 904-0103
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Naval Hospital Pensacola
Pensacola, FL 32512-0001
Who Is Using Calmare?
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Massey Cancer Center at the
Virginia Commonwealth University
Richmond, VA
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Paul Carbone Cancer Center at the
University of Wisconsin
Madison, WI
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Mayo Clinic
Rochester, MN
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Hunter Holmes McGuire Veteran’s
Hospital, Richmond, VA
Stephen J. D'Amato, MD, FACEP
West Warwick, RI
http://cprcenters.com/
Jack D'Angelo MD, MBA, Perry
Drucker MD, and Christopher
Perez MD
Staten Island, NY
http://www.sirehab.com/Scrambler%20Thera
py%20Clinical%20Research%20and%20Pre
sentations.html
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Spero Pain Clinic, St. George, UT
http://www.sperotherapy.com/
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32 Calmare® Treatment Centers
listed w/ Competitive Technologies
University of Virginia, Charlottesville,
VA
Should We Use It?
• Cost: ~ $85,000
• Options for lease vs purchase
• United Health Care, Blue Cross Blue
Shield and Medicare
• Medicare just lost appeal for
Calmare®
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Charge $60 to $300 per session
• You would need 142 patients over the
course of 2 years (6 pts/month)
charged the minimum $60/session =
$85,000
Should We Use It?
• American Academy of Pain Medicine
– Released a position paper at its annual meeting calling insurance
payers to provide adequate coverage for interdisciplinary pain care
– PT, Massage, Yoga, Acupuncture and other alternative therapies
• Clinical / ethical responsibility to offer alternative pain therapies
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Improve QOL and functionality
Reduce medication use
Outcomes help with decisions to start chemotherapy?
Use for non-cancer neuropathic pain syndromes
• Research Potential
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Clinical Research Site?
fMRI?
Blood levels of prostaglandins, endorphins?
Reduce inpatient LOS?
Demo
Demo
• Up to 5 pairs of electrodes are placed on the skin
surrounding pain region
Demo
Placement of electrodes does not always follow the dermatome.
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Demo
• Treatment session is between 30 - 60 minutes
• 10 treatments
• 1-2 times in 3-6 months if necessary
Demo
FIRST TREATMENT
Complete Analgesia
Completes
all
Treatments
Satisfactory
Analgesia
Duration
Non-Optimal
Analgesia
Duration
Requires
Treatments PRN
No Response
Carried out incorrectly or
unfeasible
(False Non-Responsive)
Carried out correctly and
actually non-responsive*
Demo
Chronic Benign Pain
Basic Cycle of two
consecutive weeks of 1012 treatments
Follow Up
(1-3 Months)
Slow Relapse
(Seen in pluriradicular pain)
Absence of Pain
Possibility of Functional Recovery
(Typically observed in monoradicular pain syndromes)
Demo
Oncology Pain
Basic Cycle of two
consecutive weeks of
10 treatments
Monitoring
Single Treatment when Needed
Absence of Pain
Possibility of Functional Recovery
(Typically observed in monoradicular pain syndromes)
Q&A
References
1.
2.
Frankish H. 15 million new cancer cases per year by 2020, says WHO. Lancet 2003; 361: 1278
Van den Beuken-van Everdingen MHJ, De Rijke JM, Kessels AG et al. Prevalence of pain in patients with cancer: a
systematic review of the past 40 years. Ann Oncol 2007; 18: 1437–1449.
3. Costantini M, Ripamonti C, Beccaro M et al. Prevalence, distress, management and relief of pain during the last three
months of cancer patients’ life. Results of an Italian mortality follow-back survey. Ann Oncol 2009; 20: 729–735.
4. Breivik H, Cherny N, Collett F et al. Cancer-related pain: a pan European survey of prevalence, treatment, and patient
attitudes. Ann Oncol 2009; 20: 1420–1433.
5. Marineo, G. Untreatable pain resulting from abdominal cancer: new hope from biophysics? JOP 4, 1–10 (2003).
6. Sabato, A.F., Marineo, G. & Gatti, A. Scrambler therapy. Minerva Anestesiol. 71, 479–482 (2005).
7. Smith, T.J., Coyne, P.J., Parker, G.L., Dodson, P. & Ramakrishnan, V. Pilot trial of a patient-specific cutaneous
electrostimulation device (MC5-A Calmare¨) for chemotherapy-induced peripheral neuropathy. J. Pain Symptom Manage.
40, 883–891 (2010).
8. Ricci, R., Pirotti, S., Scarpi E., Burgio M., Maltoni M., Sanson E., Amadori D. Managing chronic pain: results from an
open-label study using MC5-A Calmare® device. J Support Care Cancer. 20:405-412 (2012).
9. Marineo, G., Iorno, V., Gandini, C., Moschini, V. & Smith, T.J. Scrambler therapy may relieve chronic neuropathic pain
more effectively than guideline-based drug management: results of a pilot, randomized, controlled trial. J. Pain Symptom
Manage. 43:1, 87-95 (Jan 2012).
10. Pachman, D.R., et al. Pilot Study of Scrambler therapy for the treatment of chemotherapy-induced peripheral neuropathy.
2012 ASCO Annual Meeting, Abstract No 9075. J Clin Oncol 30, 2012 (supplemental).
11. Smith, T., Marineo, G. Treatment of post-herpeti pain with scrambler therapy, a patient-specific neuro-cutaneous electrical
stimulation device. 2012 ASCO Abstract No e19564. J Clin Oncol 30, 2012 (supplemental).
12. Sparadeo, F., Kaufman, C., D’Amato, S. Scrambler Therapy: An Innovative and Effective Treatment for Chronic
Neuropathic Pain. J Life Care Planning. 11:3, 3-15. (2012)
Thank You