An Open Label Study Assessing REN Treatment in Headache Management in Temporomandibular Disorders

June 7, 2026 updated by: Theranica

An Open Label, Single-arm Multicenter Study Assessing the Safety and Efficacy of Remote Electrical Neuromodulation (Ren) in the Management of Headache, Orofacial Pain, and Other Symptoms Attributed to Temporomandibular Disorders (TMD)

Temporomandibular disorders (TMD) encompass a group of conditions involving the masticatory muscles, temporomandibular joint (TMJ), and associated structures. TMD is the most common cause of non-odontogenic orofacial pain and is the second most commonly occurring musculoskeletal condition. Up to 70% of the general population experiences signs and/or symptoms of TMD, with headache presenting as one of the most common manifestations. Recent studies highlight the comorbid presence of headache and TMD, hypothesizing that a relationship likely exists between the two conditions. Headache severity has also been associated with the number of TMD symptoms such that the prevalence of headache in TMD patients. A key mechanism underlying both TMD and migraine is the deficiency in Conditioned Pain Modulation (CPM), a descending inhibitory pathway that regulates pain processing. CPM impairment has been implicated in chronic pain states, including both migraine and TMD, contributing to their frequent co-occurrence and shared pathophysiology.

Remote Electrical Neuromodulation (REN) is an emerging non-pharmacological intervention that exerts its analgesic effects by activating the CPM system, which is deficient in individuals with TMD and migraine. The Nerivio REN wearable device is FDA-cleared for acute and/or migraine prevention, in patients 8 years of age or older. Given the evidence linking CPM dysfunction to TMD pathogenesis, REN presents a promising therapeutic approach to addressing both the underlying pain dysregulation and symptom burden in affected patients.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Temporomandibular disorders (TMD) encompass a group of conditions involving the masticatory muscles, temporomandibular joint (TMJ), and associated structures. TMD is the most common cause of non-odontogenic orofacial pain and is the second most commonly occurring musculoskeletal condition. Up to 70% of the general population experiences signs and/or symptoms of TMD, with headache presenting as one of the most common manifestations. Recent studies highlight the comorbid presence of headache and TMD, hypothesizing that a relationship likely exists between the two conditions. Accordingly, a recent systematic review and meta-analysis supported a positive association between pain-related TMD, migraine, and chronic tension-type headaches. Other studies demonstrated that, among patients seeking care for headaches, the prevalence of those presenting with TMD symptoms ranged from 52-55%. Headache severity has also been associated with the number of TMD symptoms such that the prevalence of headache in TMD patients with one TMD symptom was 57%, with two symptoms was 65%, and with three or more symptoms was 73%. Notably, the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study -the largest population-based study in adults designed to identify risk factors associated with the onset and persistence of TMD - showed that prior headaches were a significant risk factor for the development of first-onset TMD symptoms9. After the development of TMD, both headache severity and frequency were shown to increase in the TMD group compared to healthy participants. Specifically, the prevalence of migraine episodes increased 10-fold in the group that developed TMD symptoms. Finally, clinical studies revealed that, when TMD is successfully treated, headache symptoms also tend to resolve, suggesting a role of TMD in the pathophysiological process.

A key mechanism underlying both TMD and migraine is the deficiency in Conditioned Pain Modulation (CPM), a descending inhibitory pathway that regulates pain processing. CPM impairment has been implicated in chronic pain states, including both migraine and TMD, contributing to their frequent co-occurrence and shared pathophysiology. Remote Electrical Neuromodulation (REN) is an emerging non-pharmacological intervention that exerts its analgesic effects by activating the CPM system, which is deficient in individuals with TMD and migraine. The Nerivio REN wearable device is FDA-cleared for acute and/or migraine prevention, in patients 8 years of age or older. It is a prescription use, self-administered device for use in the home environment at the onset of migraine headache or aura for acute treatment, or every other day for preventive treatment. By enhancing endogenous pain inhibition, REN has been shown to provide effective relief in migraine, and its application in TMD is expected to yield similar clinical benefits. Given the evidence linking CPM dysfunction to TMD pathogenesis, REN presents a promising therapeutic approach to addressing both the underlying pain dysregulation and symptom burden in affected patients.

The aim of this study is to evaluate the safety and efficacy of Nerivio Infinity for the management of headache, orofacial pain and TMD related symptoms.

This is an open-label, single arm study to determine whether REN can be utilized for the management of TMD-related pain and other symptoms. 40 participants (ages 12 years and older) with a TMD diagnosis will be enrolled. Treatment will be performed once daily for 45 minutes per treatment, for 6 weeks. Daily treatment ensures consistent neuromodulation, is expected to reduce overall pain severity, and to maintain CPM activation. TMD pathophysiology supports daily use: TMD involves central sensitization and chronic engagement of the trigeminal system, similar to migraine. Unlike migraine, where individual attacks may be separated by pain-free periods, TMD pain is often persistent or recurrent on a near-daily basis. Moreover, daily use ensures sustained neuromodulatory effects to prevent worsening of pain flares while improving functional jaw mobility. Daily use is expected to reduce overall pain severity, attack frequency, and functional impairment (aligning with migraine prevention goals). Additional acute use (as-needed adjunct to daily treatment) will be permitted and is expected to address pain flare-ups that may still occur despite daily neuromodulation.

The study will consist of two main phases:

4-week baseline phase- in which participants will report their symptoms daily via an electronic app diary (with no intervention); 6-week intervention phase- in which eligible participants perform once daily treatments using Nerivio Infinity device, and continue to report symptoms daily via the app.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Mississippi
      • Ridgeland, Mississippi, United States, 39157
    • New York
      • Commack, New York, United States, 11725
        • Recruiting
        • True North Neurology
        • Contact:
        • Principal Investigator:
          • Warren Spinner,, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Is of 12 years of age and older (inclusive; of any gender, race, or ethnicity)
  2. Meets diagnostic criteria for chronic TMD (Myalgia and/or Arthralgia) based on the Diagnostic Criteria for TMD (DC/TMD)
  3. Has experienced TMD pain for at least 6 months
  4. Has experienced TMD pain at level ≥4 on a 0-10 scale for at least 10 days of the last 30 days
  5. Commits to not making any changes to TMD treatment regime (medication and/or non-medication), including not adding or removing treatment, and if on any existing treatment then maintaining the same treatment type, dosage, and frequency from 3 months prior to enrollment to study completion
  6. Naïve to REN treatment
  7. Willing and able to understand and comply with all study procedures and be available for the duration of the study
  8. Has their own smartphone or tablet device that is connected to the internet
  9. Provides a signed and dated informed consent form

Exclusion Criteria:

  1. Has any of the following medical conditions:

    1.1 Uncontrolled seizures/epilepsy 1.2 Benign and malignant TMJ and masticatory muscle tumors 1.3 Presence of implanted electrical device

  2. Has experienced facial trauma or orofacial surgery within 6 weeks prior to the Screening and Baseline Visit
  3. Is undergoing current active orthodontic treatment
  4. Currently being treated with chemotherapy or radiation therapy
  5. Meets the ICHD-3 diagnostic criteria for migraine with or without aura, either chronic or non-chronic migraine
  6. Currently taking an opioid medication, whether episodically or daily, within 30 days prior to the Screening and Baseline Visit
  7. Has been treated with another investigational drug or treatment within 30 days prior to the Enrollment Visit
  8. Taking more than one prescription drug for the treatment of pain (including all types of drugs and modalities, e.g. pill, spray, injection) Note that this criterion does not refer to drug-free based treatments (including split therapy, physical therapy, acupuncture, massage therapy, biofeedback, CBT, or transcutaneous electrical nerve stimulation) for the treatment of pain, which may be used (single or multiple treatments) as long as not changed throughout the study.
  9. Anything that, in the opinion of the investigator, would place the participant at increased risk or preclude the participant's full compliance with or completion of the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Nerivio treatment

Nerivio, a Remote electrical neuromodulation (REN) device. The device delivers transcutaneous electrical stimulation to the upper arm to induce conditioned pain modulation (CPM) that activates a descending endogenous analgesic mechanism. The treatment is self-administered and controlled by a smartphone application.

Treatment regime - once a day
Device: Nerivio treatment
Nerivio, a Remote electrical neuromodulation (REN) device. The device delivers transcutaneous electrical stimulation to the upper arm to induce conditioned pain modulation (CPM) that activates a descending endogenous analgesic mechanism. The treatment is self-administered and controlled by a smartphone application.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in daily maximum-pain level
Time Frame: 10 weeks
The change in daily maximum-pain level (on the numeric rating scale, NRS, of 0-10) as measured by comparing the average daily maximum orofacial-pain score in the last 2 weeks of baseline phase (weeks 3-4) to the last 2 weeks of the intervention phase (weeks 9-10). Pain score will be taken from any of the orofacial locations specified in the daily diary (jaw, head, neck, ear, eye, face, teeth) that presented the maximum daily pain. Patients will log their maximum pain levels in a daily diary, through a study specific smartphone application.
10 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Jaw pain level
Time Frame: 10 weeks
Change in Jaw pain level (0-10 NRS) as measured by comparing the average daily maximum-pain score in the last 2 weeks of baseline phase (weeks 3-4) to the last 2 weeks of the intervention phase (weeks 9-10).
10 weeks
Functional changes in jaw mobility
Time Frame: 10 weeks

Functional changes in jaw mobility will be measured by a health care provider in all participants at the end of the baseline phase (visit 2) and at week 10 (visit 3) to determine whether REN improves pain-free maximum mouth opening (MMO) scores (a clinically relevant improvement being defined as >5mm).

Jaw mobility range of motion, is assessed by measuring maximum mouth opening, and side-to-side (lateral) movement
10 weeks
Change in self-reported Jaw Functional Limitation Scale (JFLS)
Time Frame: 10 weeks
Change in the self-reported Jaw Functional Limitation Scale (JFLS) from the end of the baseline phase (visit 2) to following the intervention phase at week 10 (visit 3) to compare post-treatment changes in limitations of jaw function.
10 weeks
Change in headache pain level
Time Frame: 10 weeks
Change in headache pain level (0-10 NRS) as measured by comparing the average daily maximum-pain score in the last 2 weeks of baseline phase (weeks 3-4) to the last 2 weeks of the intervention phase (weeks 9-10).
10 weeks
Change in Patient Global Impression of Change (PGIC) scores
Time Frame: 10 weeks
Compare average Patient Global Impression of Change (PGIC) scores regarding orofacial pain following the intervention at visit 3, to assess if patients perceive greater improvement with using REN.
10 weeks
Change in number of days with jaw pain
Time Frame: 10 weeks
Change in number of days with jaw pain, and with headache pain, between the last 2 weeks of baseline phase (weeks 3-4) to the last 2 weeks of the intervention phase (weeks 9-10).
10 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Theranica

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Alit Stark Inbar, PhD, Theranica

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 4, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 30, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 26, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 7, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 10, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 10, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 7, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TCH-200

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Temporomandibular Disorder

Clinical Trials on Nerivio treatment

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings