Investigation and Modulation of the Mu-opioid Mechanisms in TMD (in Vivo)

NCT03724032 | Terminated Results DMC FDA Device

• 2 other identifiers: HUM00110179U01DE025633
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, this team of researchers will investigate the impact of chronic temporomandibular disorder suffering on the endogenous μ-opioid system in vivo, arguably one of the principal endogenous pain modulatory systems in the brain, and its modulation by 10 daily sessions of primary motor cortex stimulation using high-definition transcranial direct current stimulation (HD-tDCS).

Conditions

Temporomandibular Disorder

Outcome Measures

Primary Outcomes (1)

• Change in Clinical Visual Analog Scale Pain Score From Baseline (Screening Day) to 4 Weeks After Completion of HD-tDCS Sessions (Follow Up #2).

  Change in clinical Visual Analog Scale pain score from baseline (Screening Day) to 4 weeks after completion of HD-tDCS sessions (Follow Up #2). Pain is measured on a scale of 1-10, with 10 being the worst.

  Screening (Baseline), 4 Weeks after completion of HD-tDCS sessions

Secondary Outcomes (6)

• Change in Clinical Visual Analog Scale Pain Score During Sustained Masseteric Pain Stress Challenge From Baseline PET (#1) Session to Follow-up PET (#2) Session, 1 Week After Completion of HD-tDCS Sessions.

  Baseline, 1 Week after completion of HD-tDCS sessions

• Changes in GeoPain Measures (PAINS - Summation of Area and Intensity) From Baseline Daily Over the Treatment Period and Through Follow-up (4 Weeks After Completion of HD-tDCS Sessions).

  Baseline to 4 weeks after completion of HD-tDCS sessions

• Difference in µOR BPND Levels of Thalamus From Baseline PET (#1) Session to Follow-up PET (#2) Session, 1 Week After Completion of HD-tDCS Sessions.

  Baseline to 1 Week after completion of HD-tDCS sessions.

• Change in Clinical Visual Analog Scale Pain Score at Rest From Baseline PET (#1) Session to Follow-up PET (#2) Session, 1 Week After Completion of HD-tDCS Sessions.

  Baseline, 1 Week after completion of HD-tDCS sessions.

• Difference in µOR BPND Levels at Rest During PET (#1) in Chronic TMD Patients as Compared to Healthy Subjects.

  During PET #1, at rest (5-40 mins after radiotracer injection)

Study Arms (3)

TMD Patients Active Group: Active Comparator

ACTIVE COMPARATOR

30 TMD patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\*) as 20 minute sessions, once daily for 10 days (M-F for 2 weeks).

Device: HD-tDCS*

TMD Patients Sham Group: Sham Comparator

SHAM COMPARATOR

30 TMD patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\*) as 30-second administrations at the beginning and end of each 20 minute session, once daily for 10 days (M-F for 2 weeks).

Device: Sham HD-tDCS*

Healthy Control Group

NO INTERVENTION

20 Healthy Volunteers will be asked to undergo baseline assessments only (including imaging, but no brain stimulation). Healthy volunteer data (n \</= 10) may be used from a prior study (NIDCR-R56-DE022637 project \[IRBMED #HUM00080911; Dr. Alexandre DaSilva, Principal Investigator\]). Consent to use data for a future study was obtained in the informed consent document at the time of participation.

Interventions

HD-tDCS* DEVICE

Non-invasive brain stimulation (active protocol)

Also known as: HD-tDCS (active protocol)

TMD Patients Active Group: Active Comparator

Sham HD-tDCS* DEVICE

Non-invasive brain stimulation (sham protocol)

Also known as: HD-tDCS (sham protocol)

TMD Patients Sham Group: Sham Comparator

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide signed and dated informed consent form;
• Male or female, aged 18 to 65 (inclusive);
• tDCS naïve; and
• Willing to comply with all study procedures and be available for the duration of the study.
• In addition, TMD subjects must qualify as:
• Diagnosed with chronic TMD as defined by the Diagnostic Criteria (DC) for TMD and the American Academy of Orofacial Pain (DC/TMD): "Chronic TMD pain and dysfunction for at least one year from the clinical exam session (DC/TMD: Masticatory myofacial pain with/without referral) not adequately controlled by previous therapies (eg, NSAIDs, muscle relaxants)"
• TMJ open-surgery naïve;
• TMD maximum pain score pain of greater than or equal to 3 (moderate to severe) on a 0-10 VAS, despite existing treatment, for 3 days in the 7 days preceding study consent, based on report at the screening session;
• If taking pain medications, the dose regimen must be stable for at least 4 weeks prior to screening; and
• Willing to halt the introduction of new medications for chronic TMD symptoms during the study.
• Emphasis is therefore placed on generalizability and chronicity of symptoms.
• To qualify as a Healthy Volunteer, subjects must be:
• Without self-reported history of systemic disorders or other chronic pain disorders, including migraine.

You may not qualify if:

• Existence of chronic pain disorder(s) other than TMD
• History of a traumatic brain injury
• History or current evidence of a psychotic disorder (e.g. schizophrenia) or substance abuse (self-reported)
• Bipolar or severe major depression, as evidenced by a Beck Depression Inventory score of ≥ 30
• Ongoing, unresolved disability litigation (self-reported)
• History of neurological disorder (e.g. epilepsy, stroke, neuropathy, neuropathic pain; self-reported)
• Opioid pain medications taken within the past 3 months
• Past allergic response to opioids or chemically related drugs (e.g., carfentanil)
• Excluded by MRI Center or PET Center safety screening checklist (as administered by study staff)
• Drug test positive for opioid or recreational drug (e.g., cannabis) at the time of the PET scan visits
• Pregnant or lactating (negative urine pregnancy test must be available before any PET procedures are initiated)
• Treatment with an investigational drug, device or other intervention within 30 days of study enrollment
• Anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study (e.g., medical condition, laboratory finding, physical exam finding, logistical complication).

Sponsors & Collaborators

• University of Michigan: lead
• National Institute of Dental and Craniofacial Research (NIDCR): collaborator

Study Sites (1)

University of Michigan School of Dentistry

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• Kim DJ, Nascimento TD, Lim M, Danciu T, Zubieta JK, Scott PJH, Koeppe R, Kaciroti N, DaSilva AF. Exploring HD-tDCS Effect on mu-opioid Receptor and Pain Sensitivity in Temporomandibular Disorder: A Pilot Randomized Clinical Trial Study. J Pain. 2024 Apr;25(4):1070-1081. doi: 10.1016/j.jpain.2023.11.001. Epub 2023 Nov 11.

  PMID: 37956741 DERIVED

MeSH Terms

Conditions

Temporomandibular Joint Disorders

Condition Hierarchy (Ancestors)

Craniomandibular Disorders; Mandibular Diseases; Jaw Diseases; Musculoskeletal Diseases; Joint Diseases; Muscular Diseases; Stomatognathic Diseases

Results Point of Contact

• Title: Jacqueline Dobson
• Organization: University of Michigan

contactHOPE@umich.edu

734-763-8469

Study Officials

• Alexandre F DaSilva, DDS, DMedSc

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, BMS-Prosthodontics Dept., School of Dentistry

Study Record Dates

• First Submitted: October 26, 2018
• First Posted: October 30, 2018
• Study Start: December 13, 2018
• Primary Completion: January 17, 2022
• Study Completion: January 17, 2022
• Last Updated: June 15, 2023
• Results First Posted: June 15, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)