Scrambler Trial for Pain in NMOSD

NCT ID: NCT03452176

Last Updated: 2020-05-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-21
• Study Completion Date: 2019-08-29

Brief Summary

A novel technology called Scrambler Therapy is a non-invasive pain modifying technique that utilizes transcutaneous electrical stimulation of C fibers with the intent of re-organizing maladaptive signaling pathways. This neuromodulatory therapy has been investigated for treatment of chronic neuropathic pain in several conditions including chemotherapy-induced peripheral 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. This study is a randomized single blinded, sham-controlled trial of patients with Neuromyelitis Optica Spectrum Disorder who have central neuropathic pain using Scrambler Therapy added to standardized empiric medications using patient reported outcomes to determine if Scrambler Therapy is a feasible and effective add-on treatment of chronic neuropathic pain.

This trial will recruit twenty-two adult patients diagnosed with NMOSD who have chronic neuropathic pain despite empiric treatment with an anti-epileptic, antidepressant, opioid and/or an NSAID medication. Patients will be randomized 1:1 to undergo Scrambler Therapy or blinded sham daily for 10 days. The primary outcomes will be acceptability and feasibility. The secondary outcome will be efficacy measured as a change in pain scores of more than two points recorded daily by the patient using an 11-point visual analog scale; quality of life (QoL), neurologic function, anxiety, depression, sleep disturbance and pain will also be evaluated at baseline, at the end of therapy, and at 4 & 8 weeks following completion of treatment. Investigators hypothesize that Scrambler Therapy will be an acceptable, feasible and efficacious intervention that significantly reduces pain in patients with neuromyelitis optica spectrum disorder.

Detailed Description

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system that disproportionately affects non-Caucasians and females,1,2 and has a worldwide prevalence estimated to be 0.52 to 4.4/100,000.3 NMOSD preferentially causes recurrent inflammatory attacks in the optic nerves and spinal cord, leading to blindness, paralysis and death. Despite these devastating consequences of the disease, patients have reported that pain is among the most prevalent and debilitating symptom, and impacts mood, mobility and quality of life (QoL). In particular, central neuropathic pain (CNP) is pervasive, severe, intractable to treatment, and affects 62-91% of patients with NMOSD. CNP is described as agonizing burning, stabbing, shooting, tingling or squeezing sensation that is distressing, persistent and incapacitating.13,14 The presence of CNP in NMOSD is a direct consequence of targeted immune-mediated destruction of the spinal cord and may be influenced by lesion span and location: NMOSD lesions are generally transverse, involving both the central gray matter and dorsal horns. The dorsal horns are innervated by primary ascending fibers that convey sensory information to the brain. Damage to the central gray matter in NMOSD leads to astrocytic damage and tissue necrosis, thus disrupting sensory pain tracts going to and from the brain. As a consequence of ongoing spontaneous activity arising in the periphery, surviving neurons develop increased background activity and increased responses to ascending nerve impulses, including normally harmless tactile stimulation. An additional mechanism of CNP involves peripheral sensitization of non-myelinated ascending C fibers interpreted by the brain as persistent pain, a characteristic sign of an inflammatory process in the spinal cord.

Spinal CNP typically presents weeks to months after the cord damage has occurred, long after the acute injury, and may be the result of secondary changes due to reorganization of damaged circuits of the somatosensory system. CNP occurs at and below the spinal cord lesion level, and can persist for years, decades or throughout the patient's life. As with neuropathic pain from other etiologies, the most frequently-used medications for its treatment in NMOSD are anti-epileptics, antidepressants and non-steroidal anti-inflammatory agents. Descriptive studies in NMOSD recognized the inadequate effect of these medications, resulting in frequent breakthrough opioid use. Furthermore, side effects from these medications, particularly at higher doses, are independently associated with fatigue.

Scrambler is a type of transcutaneous electrostimulation (TENS) that uses peripheral nerve stimulation to modify ascending sensory responses in the spinal cord. Electrical impulses are transmitted via surface electrodes placed surrounding the pain area. Traditional TENS units take advantage of the Gate Control Theory in which stimulation of surrounding A-delta fibers dampens incoming pain signals. Scrambler therapy provides additional stimulation of ascending sensory C fibers that imitate normal nerve action potentials with the intent of re-organizing maladaptive signaling pathways. The theory behind Scrambler treatment is that "scrambled" waveforms - instead of repetitive identical waveforms in traditional TENS - are dynamically assembled into strings of information that are interpreted by the brain to replace pain with "no-pain" information. In contrast to traditional TENS therapy that provides only short term pain relief, studies with Scrambler therapy in peripheral neuropathy suggest that patients can have significantly reduced pain or be pain-free for up to 3 months following a series of treatments, and that follow-up treatments may require fewer sessions for continued relief.

This study is a randomized single blinded, sham-controlled trial of patients with Neuromyelitis Optica Spectrum Disorder who have central neuropathic pain using Scrambler Therapy added to standardized empiric medications using patient reported outcomes to determine if Scrambler Therapy is a feasible and effective add-on treatment of chronic neuropathic pain.

This trial will recruit twenty-two adult patients diagnosed with NMOSD who have chronic neuropathic pain despite empiric treatment with an anti-epileptic, antidepressant, opioid and/or an NSAID medication. Patients will be randomized 1:1 to undergo Scrambler Therapy or blinded sham daily for 10 days. The primary outcomes will be acceptability and feasibility. The secondary outcome will be efficacy measured as a change in pain scores of more than two points recorded daily by the patient using an 11-point visual analog scale; quality of life (QoL), neurologic function, anxiety, depression, sleep disturbance and pain will also be evaluated at baseline, at the end of therapy, and at 4 & 8 weeks following completion of treatment. Investigators hypothesize that Scrambler Therapy will be an acceptable, feasible and efficacious intervention that significantly reduces pain in patients with neuromyelitis optica spectrum disorder.

Conditions

Neuromyelitis Optica

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Scrambler

This arm will receive the Scrambler intervention for 1 hour daily x10 days.

Group Type: EXPERIMENTAL

Scrambler

Intervention Type: DEVICE

Scrambler is a non-invasive pain modifying technique that utilizes transcutaneous electrical stimulation of nociceptive fibers with the intent of re-organizing maladaptive signaling pathways which has been investigated for treatment of peripheral neuropathy.

Sham-Control

This arm will receive the Sham-Control intervention for 1 hour daily x10 days.

Group Type: SHAM_COMPARATOR

Scrambler Sham Control

Intervention Type: DEVICE

Sham control should be indistinguishable to the participants from experimental Scrambler therapy.

Interventions

Scrambler

Scrambler is a non-invasive pain modifying technique that utilizes transcutaneous electrical stimulation of nociceptive fibers with the intent of re-organizing maladaptive signaling pathways which has been investigated for treatment of peripheral neuropathy.

Intervention Type: DEVICE

Scrambler Sham Control

Sham control should be indistinguishable to the participants from experimental Scrambler therapy.

Intervention Type: DEVICE

Other Intervention Names

CALMARE

Eligibility Criteria

Inclusion Criteria

• Be 18 years of age or older
• Have the presence of persistent CNP rated at a level of 4 or higher on an 11-point numeric rating scale (NRS); persistent pain is defined as presence for >3 months
• Patients must be stable in their disease, such that they have had no spinal cord relapses with the last 6 months
• Patients may use any combination of standard of care medications for pain treatment, to include anti-epileptic, antidepressant, opioid or non-steroidal anti-inflammatory medications, with no adjustments to the regimen within 30 days of enrollment.
• Aquaporin-4 (AQP4)-antibody positive or negative, or untested, but otherwise meeting criteria for diagnosis of NMOSD.

Exclusion Criteria

• A concomitant diagnosis of peripheral neuropathy
• An ongoing concomitant central neurologic disorder
• Pain that is referable to a spinal cord lesion that starts above the 4th vertebral disc of the cervical spinal cord because FDA device clearance allows for treatment below the neck
• Use of an investigational agent for pain control within 30 days of enrollment
• Pregnant or breastfeeding women
• Those with cognitive or mental incompetency
• Patients with implantable devices

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Levy, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Maureen A Mealy, RN

Role: STUDY_DIRECTOR

Johns Hopkins University

Locations

Johns Hopkins University

Baltimore, Maryland, United States

Countries

United States

References

Mealy MA, Kozachik SL, Cook LJ, Totonis L, Salazar RA, Allen JK, Nolan MT, Smith TJ, Levy M. Scrambler therapy improves pain in neuromyelitis optica: A randomized controlled trial. Neurology. 2020 May 5;94(18):e1900-e1907. doi: 10.1212/WNL.0000000000009370. Epub 2020 Apr 8.

Reference Type: DERIVED

PMID: 32269109 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00115699

Identifier Type: -

Identifier Source: org_study_id