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High Frequency Impulse Therapy for Neuropathic Pain in NMOSD

Primary Purpose

Neuromyelitis Optica

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
High Frequency Impulse Therapy
High Frequency Impulse Therapy - Sham
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuromyelitis Optica

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Experimental arm

Sham arm

Arm Description

Devices will be programmed by our study coordinator to provide a sham signal or the experimental signal. The location of the TENS electrodes 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.

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.

Outcomes

Primary Outcome Measures

Pain score on the Numerical Rating Score (NRS)
The NRS scale is an 11 point scale (0-10) with 0 as no pain and 10 as worst pain to determine the pain level.

Secondary Outcome Measures

Pain score on the NRS in the extension phase
The NRS scale is an 11 point scale (0-10) with 0 as no pain and 10 as worst pain to determine the pain level.
"Worst" pain score on the NRS scale
The NRS scale is an 11 point scale (0-10) with 0 as no pain and 10 as worst pain to determine the pain level.
Withdrawal from trial
The number of patients who withdraw because of poor compliance.
Quality of life survey
SF36 quality of life questionnaire

Full Information

First Posted
October 22, 2020
Last Updated
June 6, 2023
Sponsor
Massachusetts General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04614454
Brief Title
High Frequency Impulse Therapy for Neuropathic Pain in NMOSD
Official Title
High Frequency Impulse Therapy for Neuropathic Pain in NMOSD
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 7, 2021 (Actual)
Primary Completion Date
April 13, 2022 (Actual)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
The aim of this study is to determine whether self-administered, at-home use of a transcutaneous electrical nerve stimulating device is an effective, acceptable and feasible method of relief from neuropathic pain among patients with Neuromyelitis optica spectrum disorder (NMOSD).
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 home TENS 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 TENS device for this study 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuromyelitis Optica

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Subjects will be randomized to either the intervention or the control group, fitted and trained to use the home TENS 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.
Allocation
Randomized
Enrollment
46 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental arm
Arm Type
Experimental
Arm Description
Devices will be programmed by our study coordinator to provide a sham signal or the experimental signal. The location of the TENS electrodes 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.
Arm Title
Sham arm
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
High Frequency Impulse Therapy
Other Intervention Name(s)
Transcutaneous electrical nerve stimulation
Intervention Description
The home TENS unit 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.
Intervention Type
Device
Intervention Name(s)
High Frequency Impulse Therapy - Sham
Other Intervention Name(s)
Transcutaneous electrical nerve stimulation - Sham
Intervention Description
This device looks like the experimental device but does not provide the electrical current.
Primary Outcome Measure Information:
Title
Pain score on the Numerical Rating Score (NRS)
Description
The NRS scale is an 11 point scale (0-10) with 0 as no pain and 10 as worst pain to determine the pain level.
Time Frame
4 weeks from baseline to completion of the experimental phase.
Secondary Outcome Measure Information:
Title
Pain score on the NRS in the extension phase
Description
The NRS scale is an 11 point scale (0-10) with 0 as no pain and 10 as worst pain to determine the pain level.
Time Frame
4 weeks from end of the experimental phase to end of the open label phase.
Title
"Worst" pain score on the NRS scale
Description
The NRS scale is an 11 point scale (0-10) with 0 as no pain and 10 as worst pain to determine the pain level.
Time Frame
4 weeks from baseline to completion of the experimental phase.
Title
Withdrawal from trial
Description
The number of patients who withdraw because of poor compliance.
Time Frame
4 weeks from baseline to completion of the experimental phase.
Title
Quality of life survey
Description
SF36 quality of life questionnaire
Time Frame
4 weeks from baseline to completion of the experimental phase.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Men and women 18 years of age or older diagnosed with NMOSD per the 2015 NMOSD criteria Patients must be positive for the aquaporin-4 antibody in serum. Presence of persistent neuropathic pain (>3 months) rated at a level of 4 or higher on the Wong-Baker Faces Pain Scale Patients must be stable in their disease, such that they have had no spinal cord relapses within 6 months prior to enrollment 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 Pain must be localized to a spinal cord lesion Patient understands the study regimen, its requirements, risks, and discomforts, and is able and willing to sign an informed consent form Exclusion Criteria: Patients who are cognitively or mentally incompetent 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.). Use of an investigational agent for pain control concurrently or within the past 30 days History of an allergic reaction or previous intolerance to transcutaneous electronic nerve stimulation or to latex Patients with implantable drug delivery systems, e.g. Medtronic Synchromed. 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) Patients with a known history of myocardial infarction or ischemic heart disease within the past six months Prior celiac plexus block, or other neurolytic pain control treatment, within 1 month 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 Skin conditions such as open sores that would prevent proper application of the electrodes Patients with an ongoing concomitant central neurologic disorder or history of epilepsy, brain damage, or symptomatic brain metastases Other medical or other condition(s) that in the opinion of the investigators might compromise the objectives of the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Levy, MD, PhD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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High Frequency Impulse Therapy for Neuropathic Pain in NMOSD

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