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

NCT07639944 | Recruiting FDA Device

• 1 other identifier: TCH-200
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Temporomandibular Disorder

Keywords

TMD; Nerivio; Headache

Outcome Measures

Primary Outcomes (1)

• Change in daily maximum-pain level

  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 Outcomes (6)

• Change in Jaw pain level

  10 weeks

• Functional changes in jaw mobility

  10 weeks

• Change in self-reported Jaw Functional Limitation Scale (JFLS)

  10 weeks

• Change in headache pain level

  10 weeks

• Change in Patient Global Impression of Change (PGIC) scores

  10 weeks

Study Arms (1)

Nerivio treatment

EXPERIMENTAL

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

Interventions

Nerivio treatment DEVICE

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.

Nerivio treatment

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Is of 12 years of age and older (inclusive; of any gender, race, or ethnicity)
• Meets diagnostic criteria for chronic TMD (Myalgia and/or Arthralgia) based on the Diagnostic Criteria for TMD (DC/TMD)
• Has experienced TMD pain for at least 6 months
• Has experienced TMD pain at level ≥4 on a 0-10 scale for at least 10 days of the last 30 days
• 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
• Naïve to REN treatment
• Willing and able to understand and comply with all study procedures and be available for the duration of the study
• Has their own smartphone or tablet device that is connected to the internet
• Provides a signed and dated informed consent form

You may not qualify if:

• Has any of the following medical conditions:
• Uncontrolled seizures/epilepsy 1.2 Benign and malignant TMJ and masticatory muscle tumors 1.3 Presence of implanted electrical device
• Has experienced facial trauma or orofacial surgery within 6 weeks prior to the Screening and Baseline Visit
• Is undergoing current active orthodontic treatment
• Currently being treated with chemotherapy or radiation therapy
• Meets the ICHD-3 diagnostic criteria for migraine with or without aura, either chronic or non-chronic migraine
• Currently taking an opioid medication, whether episodically or daily, within 30 days prior to the Screening and Baseline Visit
• Has been treated with another investigational drug or treatment within 30 days prior to the Enrollment Visit
• 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.
• 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

Sponsors & Collaborators

• Theranica: lead

Study Sites (2)

Proven Endpoints

Ridgeland, Mississippi, 39157, United States

RECRUITING

True North neurology

Commack, New York, 11725, United States

RECRUITING

MeSH Terms

Conditions

Temporomandibular Joint Disorders; Headache

Condition Hierarchy (Ancestors)

Craniomandibular Disorders; Mandibular Diseases; Jaw Diseases; Musculoskeletal Diseases; Joint Diseases; Muscular Diseases; Stomatognathic Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Alit Stark Inbar, PhD

  Theranica

  STUDY DIRECTOR

Central Study Contacts

Dagan Harris, PhD

CONTACT

+972542220121; daganh@theranica.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label, single arm

Study Record Dates

• First Submitted: May 26, 2026
• First Posted: June 10, 2026
• Study Start: May 4, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 30, 2027
• Last Updated: June 10, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)