High Frequency Impulse Therapy for Neuropathic Pain in NMOSD

• ClinicalTrials.gov Identifier: NCT04614454
• Recruitment Status: Not yet recruiting
• First Posted: November 4, 2020
• Last Update Posted: November 17, 2020
• Sponsor: Harvard Medical School
• Collaborator: Thimble Bioelectronics, Inc.
• Information provided by (Responsible Party): Michael Levy, Harvard Medical School

Study Description

Brief Summary:

The aim of this study is to determine whether self-administered, at-home use of ENSO therapy, a high frequency impulse neuromodulation device, is an effective, acceptable and feasible method of relief from neuropathic pain among patients with Neuromyelitis optica spectrum disorder (NMOSD).

Condition or disease	Intervention/treatment	Phase
Neuromyelitis Optica	Device: High Frequency Impulse Therapy; Device: High Frequency Impulse Therapy - Sham	Phase 2

Detailed Description:

Neuromyelitis optica spectrum disorder (NMOSD) is a chronic relapsing autoimmune disease of the central nervous system (CNS) that preferentially targets the optic nerves and spinal cord, leading to paralysis, blindness and death. NMOSD is a rare disease that affects approximately 4,000-8,000 (8,000 - 15,000) people in the United States, disproportionately affects non-Caucasians and females, and has a worldwide prevalence estimated to be 0.52 to 4.4/100,000. Pain is a severely disabling component of the disease with up to 91% of patients reporting central neuropathic pain (CNP) characterized by agonizing burning, shooting or tingling sensation in the face, arms, torso and legs. NMOSD lesions in the spinal cord are characteristically long and destructive, and pain is more prevalent in NMOSD than in most other neurological diseases. Research on the impact of persistent pain on quality of life (QoL) in NMOSD has found that those patients with CNP experience more depression, less enjoyment of life, and more difficulty with ambulation. Currently, there is no standard of care for CNP treatment and off-label use of medications typically used for diabetic peripheral neuropathy are often insufficient. NMOSD is a devastating disease and there remains a high unmet need for effective treatment of CNP.

Transcutaneous electrical nerve stimulation (TENS) therapy is a non-invasive pain modifying intervention that utilizes transcutaneous electrical stimulation of ascending (sensory) fibers with the intent of re-organizing maladaptive signaling pathways. This neuromodulatory therapy has been investigated for treatment of persistent peripheral neuropathic pain in several conditions including chemotherapy-induced neuropathy, post-herpetic neuralgia and post-surgical neuropathic pain with promising results. Patients report sustained relief after undergoing daily treatment sessions for 10 consecutive weekdays.

Recently the investigators completed a sham controlled trial using a TENS unit called Scrambler in NMOSD patients showing a meaningful reduction in neuropathic pain compared to controls. The Scrambler device must be operated in an office by a professional technician, thereby limiting its usefulness to the wider NMOSD population. The ENSO device is similar to the Scrambler unit in that it provides non-invasive transcutaneous electrical impulses to reduce pain. It is a small, wearable device that utilizes both high and low frequencies to create a nerve-block effect based on the same gating theory. Because the ENSO device is programmable remotely, a controlled trial can be conducted while keeping the patient blinded to the trial arm.

For patients with NMOSD and other conditions that cause pain originating in the central nervous system, non-obtrusive, non-pharmacological devices might prove a viable alternative to pain medications. Pharmaceutical treatments for pain such as opioids have led to addiction and life-style changes with unacceptable side effects. Cost and side effects are concerns with other pharmacologic therapies for pain. In addition, in efforts to control pain, many patients are prescribed multiple medications, and then have to cope with the complexities and hazards of polypharmacy. Most importantly, none of the pharmaceutical treatments for pain in NMOSD have been proven effective in a trial.

If it can be shown among a significant patient cohort that a safe and effective at-home nonpharmacological pain therapy is available for patients with NMOSD, it would be life altering for a great many - not only those with NMOSD, but also with related neuroimmune disorders and other conditions with central neuropathic pain.

The goal of this project is to provide an effective, non-invasive treatment for neuropathic pain in NMOSD that can be safely employed at home. Many NMOSD patients have such chronic pain and/or disability that frequent visits to the clinic for therapy is difficult, if not impossible, in the best of times. Secondly, safe at-home treatments that offer continuous relief of pain (and potentially other co-occurring symptoms) can improve quality of life immensely during this, and likely future times of social distancing, when leaving home is dangerous, especially for a population on lifelong immune suppressants. Also, an at-home therapeutic option will save both time and money for patients.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Patients will be randomized 1:1 to receive treatment daily for 4 consecutive weeks versus sham, followed by an open-label phase for additional 4 consecutive weeks.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Subjects will be randomized to either the intervention or the control group, fitted and trained to use an ENSO device to self-administer treatment for at least one hour each day. The subjects will not know to which arm they are randomized. Neither will the study coordinator or the investigator. Only a 3rd party collaborator will know the assignment scheme and this will be revealed in blocks every time 4 subjects complete the trial.
• Primary Purpose: Treatment
• Official Title: High Frequency Impulse Therapy for Neuropathic Pain in NMOSD
• Estimated Study Start Date: December 1, 2020
• Estimated Primary Completion Date: June 30, 2021
• Estimated Study Completion Date: October 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Experimental arm; Devices will be programmed by our study coordinator to provide a sham signal or the experimental signal. The location of the ENSO device will be determined by the location of the pain with the goal of placing the unit at the top of the dermatological level corresponding to the pain. The study coordinator will assist each subject to place the device appropriately. Treatment will be administered for 1 hour per day for 4 weeks.	Device: High Frequency Impulse Therapy; The ENSO High Frequency Impulse Therapy device is an at-home transcutaneous electrical nerve stimulation unit in that it provides non-invasive transcutaneous electrical impulses to reduce pain. It is a small, wearable device that utilizes both high and low frequencies to create a nerve-block effect based on the same gating theory.; Other Name: Transcutaneous electrical nerve stimulation
Sham Comparator: Sham arm; The sham unit looks identical to the experimental unit. There may be a sensation experienced by subjects with the sham device but it does not deliver an electric current as the experimental units. The study coordinator will assist each subject to place the device appropriately. Treatment will be administered for 1 hour per day for 4 weeks.	Device: High Frequency Impulse Therapy - Sham; This device looks like the experimental device but does not provide the electrical current.; Other Name: Transcutaneous electrical nerve stimulation - Sham

Outcome Measures

Primary Outcome Measures :

1. Pain score on the Wang Baker Pain scale [ Time Frame: 4 weeks from baseline to completion of the experimental phase. ]
   The Wang Baker pain scale is an 11 point scale (0-10) that uses faces to assist in the determination of the pain level.

Secondary Outcome Measures :

1. Pain score on the Wang Baker Pain scale [ Time Frame: 4 weeks from end of the experimental phase to end of the open label phase. ]
   The Wang Baker pain scale is an 11 point scale (0-10) that uses faces to assist in the determination of the pain level.
2. "Worst" pain score on the Wang Baker Pain scale [ Time Frame: 4 weeks from baseline to completion of the experimental phase. ]
   The Wang Baker pain scale is an 11 point scale (0-10) that uses faces to assist in the determination of the pain level.
3. Withdrawal from trial [ Time Frame: 4 weeks from baseline to completion of the experimental phase. ]
   The number of patients who withdraw because of poor compliance.
4. Quality of life survey [ Time Frame: 4 weeks from baseline to completion of the experimental phase. ]
   SF36 quality of life questionnaire

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Men and women 18 years of age or older diagnosed with NMOSD per the 2015 NMOSD criteria
2. Patients must be positive for the aquaporin-4 antibody in serum.
3. Presence of persistent neuropathic pain (>3 months) rated at a level of 4 or higher on the Wong-Baker Faces Pain Scale
4. Patients must be stable in their disease, such that they have had no spinal cord relapses within 6 months prior to enrollment
5. Patients must be on a stable medication regimen that may include anti-epileptic, antidepressant, or non-steroidal anti-inflammatory medications, with no adjustments to the regimen within 30 days of enrollment
6. Pain must be localized to a spinal cord lesion
7. Patient understands the study regimen, its requirements, risks, and discomforts, and is able and willing to sign an informed consent form

Exclusion Criteria:

1. Patients who are cognitively or mentally incompetent
2. Any of the following: pregnant women, nursing women, women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, abstinence, etc.).
3. Use of an investigational agent for pain control concurrently or within the past 30 days
4. History of an allergic reaction or previous intolerance to transcutaneous electronic nerve stimulation or to latex
5. Patients with implantable drug delivery systems, e.g. Medtronic Synchromed.
6. Patients with heart stents or metal implants such as pacemakers, automatic defibrillators, cochlear implants, aneurysm clips, vena cava clips and skull plates (Metal implants for orthopedic repair, e.g. pins, clips, plates, cages, joint replacements are allowed)
7. Patients with a known history of myocardial infarction or ischemic heart disease within the past six months
8. Prior celiac plexus block, or other neurolytic pain control treatment, within 1 month
9. Other identified causes of painful parasthesias existing prior to chemotherapy (e.g., carpal tunnel syndrome, B12 deficiency, AIDS, monoclonal gammopathy, diabetes, heavy metal poisoning amyloidosis, syphilis, hyperthyroidism or hypothyroidism, inherited neuropathy, etc.) that might be responsible for the patient's current neuropathic symptoms
10. Skin conditions such as open sores that would prevent proper application of the electrodes
11. Patients with an ongoing concomitant central neurologic disorder or history of epilepsy, brain damage, or symptomatic brain metastases
12. Other medical or other condition(s) that in the opinion of the investigators might compromise the objectives of the study

Contacts and Locations

Contacts

Contact: Gabriela M Romanow; 617-784-2598; gromanow@mgh.harvard.edu

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Contact: Gabriela Romanow gromanow@mgh.harvard.edu

Sponsors and Collaborators

Harvard Medical School

Thimble Bioelectronics, Inc.

Investigators

• Principal Investigator: Michael Levy, MD, PhD; Massachusetts General Hospital

More Information

• Responsible Party: Michael Levy, Associate Professor, Harvard Medical School
• ClinicalTrials.gov Identifier: NCT04614454
• Other Study ID Numbers: 2020P003301
• First Posted: November 4, 2020
• Last Update Posted: November 17, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Neuralgia; Neuromyelitis Optica; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Myelitis, Transverse; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Demyelinating Diseases; Eye Diseases; Autoimmune Diseases; Immune System Diseases