Treatment of Fibromyalgia With the FibroNova Neuromodulation Device

A Prospective, Randomized, Double-blind, Sham-controlled Clinical Study Assessing the Safety and Efficacy of FibroNova for the Treatment of Fibromyalgia.

Fibromyalgia (FM) is a chronic disorder that affects the musculoskeletal system, causing widespread pain, tenderness, and fatigue. It is estimated to affect 1-5% of the population. The primary symptom of fibromyalgia is widespread pain throughout the body, accompanied by tenderness and sensitivity to pressure.

Pharmacological treatments include drugs such as antidepressants, anticonvulsants, and painkillers. Another treatment option for fibromyalgia is the use of devices such as Quell. Other non-pharmacological treatment options for fibromyalgia include cognitive-behavioral therapy (CBT), biofeedback, and relaxation techniques.

Remote Electrical Neuromodulation (REN) is a non-pharmacological technology that induces subthreshold, non-painful neurostimulation signals that activate an endogenic pain-management system termed Conditioned Pain Modulation (CPM), to produce generalized pain relief in remote body areas. Multiple studies have shown that REN is safe and effective for the acute treatment of migraine in adults and adolescents, as well as migraine prevention.

The current study examines the safety and efficacy of REN technology, implemented via the FibroNova device for treating fibromyalgia pain and related symptoms.

Study Overview

• Status: Recruiting
• Conditions: Fibromyalgia
• Intervention / Treatment: Device: FibroNova (Active mode); Device: FibroNova (Sham mode)

Detailed Description

Background Fibromyalgia (FM) is a chronic disorder that affects the musculoskeletal system, causing widespread pain, tenderness, and fatigue. It is estimated to affect 1-5% of the population. The primary symptom of fibromyalgia is widespread pain throughout the body, accompanied by tenderness and sensitivity to pressure. Secondary symptoms include fatigue, sleep disturbances, cognitive difficulties, headaches, depression, and anxiety. The exact cause of fibromyalgia is unknown, but it is believed to involve a combination of neurobiological, genetic, and environmental factors.

There is no cure for fibromyalgia, and only a minority of fibromyalgia patients continue taking medications for more than a short period due to either lack of efficacy, side effects, or both. Pharmacological treatments include drugs such as antidepressants, anticonvulsants, and painkillers, and operate by modulating pain signals in the brain and nervous system. Another treatment option for fibromyalgia is the use of devices, such as the Quell device by Neurometrix 3. Other non-pharmacological treatment options for fibromyalgia include cognitive-behavioral therapy (CBT), biofeedback, and relaxation techniques 2.

Remote Electrical Neuromodulation (REN) is a non-pharmacological technology that induces subthreshold, non-painful neurostimulation signals that activate an endogenic pain-management system termed Conditioned Pain Modulation (CPM), to produce generalized pain relief in remote body areas. Multiple studies have shown that REN is safe and effective for the acute treatment of migraine in adults and adolescents, as well as migraine prevention.

The CPM system, which is deficient in patients with migraine, has been shown to be abnormal in fibromyalgia patients as well, suggesting that fibromyalgia patients could potentially benefit from activating the CPM via REN. The current study aims to examine the safety and efficacy of REN technology, implemented via the FibroNova device for the treatment of fibromyalgia pain and related symptoms.

The FibroNova device

The device is a wireless wearable battery-operated stimulation unit controlled by a smartphone software application. Treatments with FibroNova are self-administered by the user. The FibroNova device includes several main components:

• A pair of electrodes covered with hydrogel and a removeable protective film
• An electronic circuitry and a battery contained in a plastic case
• A software that includes firmware and a software application for mobile platforms
• An armband to improve the adhesiveness and enable a discreet treatment

The study design A prospective, randomized, double-blind, sham-controlled trial. The ratio between treatment and control groups will be 1:1, stratified by prior use of prescribed medications for FM (up to 2 vs. 3 or more). the following are considered as FM medications for the stratification: Dulloxetine, Pregabalin, Milnacipran, Amitriptyline.

The study will consist of two main phases and a voluntary open-label extension phase:

4-week baseline phase- in which participants will report their symptoms daily via an electronic app diary (with no intervention);

12-week intervention phase- in which eligible participants perform two treatments per day (using FibroNova/identical looking sham (placebo) device, according to randomization), and continue to report symptoms daily via the app.

12-week open-label extension phase (OLE)- upon completion of the intervention phase, eligible participants will be offered to participate in an additional voluntary 12-week period in which they will receive active treatment.

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dagan Harris; Phone Number: +97272 3909752; Email: daganh@theranica.com
• Study Contact Backup: Name: Liron Rabani; Phone Number: +97272 3909752; Email: Lironr@theranica.com

Study Locations

• Israel
  • Tel Aviv, Israel, 6423906
    • Not yet recruiting
    • Tel Aviv Sourasky Medical Center
    • Contact: Sara Pel; Phone Number: +972-52-4266605; Email: sarap@tlvmc.gov.ii
    • Principal Investigator: Ori Elkayam, MD
• United States
  • Missouri
    • Chesterfield, Missouri, United States, 63005
      • Recruiting
      • Clinical Research Professionals
      • Contact: Shahmir Kahn; Phone Number: 636-220-1200; Email: skhan@clinicalresearchprofessionals.net
      • Principal Investigator: Daniel Mattson, MD
    • Springfield, Missouri, United States, 65807
      • Recruiting
      • ClinVest Headlands Research
      • Principal Investigator: David True, MD
      • Contact: Brittni kendrick; Phone Number: 417-883-7889; Email: brittni.kendrick@clinvest.com
  • Virginia
    • Virginia Beach, Virginia, United States, 23454
      • Recruiting
      • Gershon Pain Specialists
      • Principal Investigator: Steven Gershon, MD
      • Contact: Erika Dorman; Phone Number: 757-496-2050; Email: edorrman@gershonpain.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient age is 18-70.
2. Meets ACR 2010 Diagnostic Criteria for FM.
3. Naïve to Nerivio and to FibroNova devices.
4. Possesses the basic cognitive and motor skills needed to operate his/her own smartphone.
5. Must be able and willing to comply with the protocol.
6. Must be able and willing to provide written informed consent.

Exclusion Criteria:

1. Change in prescribed medications for pain and/or fibromyalgia in the two months prior to enrolment.
2. Pregnant or lactating.
3. Has other significant comorbidities or pain problem(s) or undergoing specific therapies that in the opinion of the investigator may confound the study assessments.(e.g. active inflammatory joint disease, including spondyloarthropathy, or active malignancy, excluding Basal cell carcinoma).
4. Newly diagnosed with fibromyalgia (under six months).
5. Is currently implanted with an electrical and/or neurostimulation device (e.g., cardiac pacemaker or defibrillator, vagus nerve neurostimulator, deep brain stimulator, spinal stimulator, bone growth stimulator cochlear implant, Sphenopalatine ganglion stimulator bladder stimulator or Occipital nerve stimulator).
6. Known uncontrolled epilepsy.
7. Active substance use disorder that could interfere with study participation.
8. Use of opioids during the 2 months prior to enrolment.
9. Has undergone nerve block (occipital or other) during the 2 months prior to enrolment.
10. Patients with severe depression, and/or suicidality
11. Is participating in any other clinical study.
12. Use of a neuromodulation device specifically indicated for FM ( e.g.Quell ) currently or in the 2 months prior to enrolment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment with active FibroNova device; Treatment of Fibromyalgia pain and symptoms with active FibroNova device. Participants will treat with an active device twice a day.	Device: FibroNova (Active mode); FibroNova neurostimulator of conditional pain modulation (CPM)
Placebo Comparator: Treatment with Sham FibroNova device; Treatment of Fibromyalgia pain and symptoms with Sham FibroNova device. Participants will treat with a sham device twice a day.	Device: FibroNova (Sham mode); FibroNova neurostimulator with an electrical output not intended for neurostimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean reduction in pain level during the last 14 days of the treatment phase (weeks 15 through 16) compare to the last 14 days of baseline phase (weeks 3 through 4)	Mean change, from the last two weeks (weeks 3-4) of the baseline phase to the last two weeks (weeks 15-16) of the intervention phase, in the 2-week average of daily self-reported pain severity scores on NRS (0 to 10) that is based on the FIQR pain item.	16 weeks
Device safety (rate of adverse events and device related adverse events)	The incidence of adverse events in general and by seriousness, severity and association to the device.	28 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in the Revised Fibromyalgia Impact Questionnaire FIQR total score	Mean change in the Revised Fibromyalgia Impact Questionnaire FIQR total score from the end of the baseline phase (end of week 4) to the end of the intervention.phase (end of week 16)	16 weeks
Mean change in FIQR functionality sub-scale score	Mean change in FIQR functionality sub-scale score from the end of the baseline phase (end of week 4) to the end of the intervention.phase (end of week 16)	16 weeks
Mean change in FIQR pain item score	Mean change in FIQR pain item score from the end of the baseline phase (end of week 4) to the end of the intervention.phase (end of week 16)	16 weeks
Mean change in Brief Pain Inventory (BPI) score	Mean change in Brief Pain Inventory (BPI) from the end of the baseline phase (end of week 4) to the end of the intervention.phase (end of week 16)	16 weeks
Improvement in patient global impression according to PGIC score	Percentage of participants who were categorized as "Improved (Very Much Improved, Much Improved, or Minimally Improved)" According to the Patient Global Impressions of Change (PGIC) at the end of week 12.	16 weeks
Mean reduction in functional disability during the last 14 days of the treatment phase (weeks 15 through 16) compare to the last 14 days of baseline phase (weeks 3 through 4)	Mean change, from the last two weeks of the baseline phase (weeks 3-4 to the last two weeks of the intervention phase (weeks 15-16), in the 2-week average of daily self-reported functional disability scores on NRS (0 to 10) that is based on the FIQR disability item.	16 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in quality of life	Mean change, from baseline to end of the intervention phase according to SF-36 quality of life questionnaire total score.	16 weeks
Improvement in sleep quality	Mean change, from the last two weeks of the baseline phase (weeks 3-4) to the last two weeks of the intervention phase (weeks 15-16), in the 2-week average of daily self-reported level of sleep quality, on an 11-level scale (based on the FIQR item), where 0 is "perfect sleep" and 10 is "could not sleep at all".	16 weeks
Mean change in level of depression	Mean change, from the last two weeks of the baseline phase (weeks 3-4) to the last two weeks of the intervention phase (weeks 15-16), in the 2-week average of daily self-reported level of depression on a 11-level scale (based on the FIQR item), where 0 is "not depressed at all" and 10 is "most depressed ever".	16 weeks
Mean change in level of anxiety	Mean change, from the last two weeks of the baseline phase (weeks 3-4) to the last two weeks of the intervention phase (weeks 15-16), in the 2-week average of daily self-reported level of anxiety, on a 11-level scale (based on the FIQR item), where 0 is "not anxious at all" and 10 is "most extremely anxious".	16 weeks
Mean change in level of cognitive impairment	Mean change, from the last two weeks of the baseline phase (weeks 3-4) to the last two weeks of the intervention phase (weeks 15-16), in the 2-week average of daily self-reported level of cognitive impairment on an 11-level scale (based on the FIQR item), where 0 is "no cognitive impairment at all" and 10 is "most severe impairment".	16 weeks
Mean change in level of cognitive presenteeism	Mean change, from the last two weeks of the baseline phase (weeks 3-4) the the last two weeks of the intervention phase (weeks 15-16), in the 2-week average daily self-reported occurrence of presenteeism on a dichotomous answer (based on the FIQR item), where 0 is "No, I felt as productive as usual at work (or school)" and 1 is "Yes, I felt greatly unproductive at work (or school).	16 weeks
Mean reduction of at least 30% in pain level	Percentage of patients with average reduction of 30% or more in pain intensity (NRS) - from the last two weeks of the baseline phase (weeks 3-4) the the last two weeks of the intervention phase (weeks 15-16).	16 weeks
Rate of treatment tolerability	Percentage of participants who indicated that the treatment was well tolerated or above, according to a multiple-choice question filled out at the end of the study (end of OLE/ upon withdrawal).	28 weeks
User experience	Percentage of participants that reported a positive user experience, based on the self-report user experience questions.	28 weeks
Patient Global Impression- change (PGI-C	Percentage of patients with an 'improved' PGI-C score at the end of week 12 of the intervention phase.	28 weeks
Patient Global Impression- change (PGI-C)- mid study:	Percentage of patients with an 'improved' PGI-C score at the mid-intervention phone call follow-up.	16 weeks

Collaborators and Investigators

• Sponsor: Theranica
• Investigators: Study Chair: Daniel Clauw, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2024
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: February 14, 2024
• First Submitted That Met QC Criteria: February 14, 2024
• First Posted (Actual): February 22, 2024

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Neuromodulation; fibromyalgia
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Myofascial Pain Syndromes
• Other Study ID Numbers: TCH101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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