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Trial record 8 of 15 for:    Temporomandibular Joint Disorders | NIH

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

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ClinicalTrials.gov Identifier: NCT03724032
Recruitment Status : Recruiting
First Posted : October 30, 2018
Last Update Posted : December 17, 2018
Sponsor:
Collaborator:
National Institute of Dental and Craniofacial Research (NIDCR)
Information provided by (Responsible Party):
Alexandre DaSilva, DDS, MS, University of Michigan

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).

Condition or disease Intervention/treatment Phase
Temporomandibular Disorder Device: HD-tDCS* Device: Sham HD-tDCS* Not Applicable

Detailed Description:
Approximately 10% of TMD patients will not experience an improvement of their symptoms and around 75% of patients who fail to respond to conservative treatments are also not suitable for TM joint surgery. Initial studies from NIH-NIDCR R56 project using positron emission tomography (PET) with [11C] Carfentanil, a selective radiotracer for μ-opioid receptor (μOR), have demonstrated that there is a decrease in thalamic μOR availability (non displaceable binding potential BPND) in the brains of TMD patients during masseteric pain compared to healthy controls. μ-opioid neurotransmission is arguably one of the mechanisms most centrally involved in pain regulation and experience. Moreover, the thalamus is the major relay structure in the forebrain for (non)-noxious inputs, which will be distributed subsequently to multiple cortical areas for discriminative, cognitive and affective processing. MRI-based reports have found that those findings co-localize with neuroplastic changes in trigeminal pain patients. Conventional therapies are unable to selectively target the thalamus and associated regions, and there is a paucity of data on how to reverse neuroplastic molecular mechanisms when available medications fail. Interestingly, several studies with motor cortex stimulation (MCS) have shown that epidural electrodes in the primary motor cortex (M1) are effective in providing analgesia in patients with central pain and that it occurs via indirect modulation of thalamic activity. Evidently, the invasive nature of such a procedure limits its indication to highly severe pain disorders. New non-invasive neuromodulatory methods for M1, such as transcranial direct current stimulation (tDCS), can now safely modulate the μOR system, providing relatively lasting pain relief in pain patients. Recently, a novel high-definition tDCS (HD-tDCS) montage created by this research group was able to reduce exclusively "contralateral" sensory-discrimative clinical pain measures (intensity/area) in TMD patients by targeting precisely the M1 region. Therefore, the main goals of this study are: First, to exploit the μ-opioidergic dysfunction in vivo in TMD patients compared to healthy controls; Second, to determine whether 10 daily sessions of noninvasive and precise M1 HD-tDCS have a modulatory effect on clinical and experimental pain measures in TMD patients; and Third, to investigate whether repetitive active M1 HD-tDCS induces/reverts μOR BPND changes in the thalamus and other pain-related regions, and whether those changes are correlated with TMD pain measures. The studies above represent a change in paradigm in TMD research, as this research group directly investigates and modulates in vivo one of the most important endogenous analgesic mechanisms in the brain.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Investigation and Modulation of the Mu-opioid Mechanisms in TMD (in Vivo)
Actual Study Start Date : December 13, 2018
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: TMD Patients Active Group: 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*
Non-invasive brain stimulation (active protocol)
Other Name: HD-tDCS (active protocol)

Sham Comparator: TMD Patients Sham Group: 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*
Non-invasive brain stimulation (sham protocol)
Other Name: HD-tDCS (sham protocol)

No Intervention: Healthy Control Group

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.




Primary Outcome Measures :
  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). [ Time Frame: Screening (Baseline), 4 Weeks after completion of HD-tDCS sessions ]
    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.


Secondary Outcome Measures :
  1. Change in clinical Visual Analog Scale pain score at rest and 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. [ Time Frame: Baseline, 1 Week after completion of HD-tDCS sessions ]
    Change in clinical Visual Analog Scale pain score at rest and 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.

  2. Changes in GeoPain measures (pain area, intensity, and their summation) from baseline daily over the treatment period and through follow-up (1, 4, and 8 weeks after completion of HD-tDCS sessions). [ Time Frame: Baseline, 1, 4, and 8 weeks after completion of HD-tDCS sessions ]
    Short- and long-term changes in GeoPain measures (percentage of pain area extension in the head region, average of pain intensity in the affected region, and their summation, meaning percentage of combined pain area and intensity in the affected region) from baseline daily over the treatment period and through follow-up (1, 4, and 8 weeks after completion of HD-tDCS sessions).

  3. Change in µOR BPND levels from baseline PET (#1) session to follow-up PET (#2) session, 1 week after completion of HD-tDCS sessions. [ Time Frame: Baseline, 1 Week after completion of HD-tDCS sessions. ]
    Change in µOR BPND levels from baseline PET (#1) session to follow-up PET (#2) session, 1 week after completion of HD-tDCS sessions.

  4. Change in clinical Visual Analog Scale pain score from baseline PET (#1) session to follow-up PET (#2) session, 1 week after completion of HD-tDCS sessions. [ Time Frame: Baseline, 1 Week after completion of HD-tDCS sessions. ]
    Change in clinical Visual Analog Scale pain score from baseline PET (#1) session to follow-up PET (#2) session, 1 week after completion of HD-tDCS sessions.

  5. Change in µOR BPND levels at rest and during experimental sustained masseteric pain stress challenge during PET (#1) in chronic TMD patients as compared to healthy subjects. [ Time Frame: During PET #1, up to 90 minutes ]
    Change in µOR BPND levels at rest and during experimental sustained masseteric pain stress challenge during PET (#1) in chronic TMD patients as compared to healthy subjects.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

OR

To qualify as a Healthy Volunteer, subjects must be:

  • Without self-reported history of systemic disorders or other chronic pain disorders, including migraine.

Exclusion Criteria:

  • 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03724032


Contacts
Contact: Diana Burnett 734-615-9390 contactHOPE@umich.edu
Contact: Thiago Nascimento, DDS, MS 734-763-8469 contactHOPE@umich.edu

Locations
United States, Michigan
University of Michigan School of Dentistry Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Diana Burnett    734-615-9390    contactHOPE@umich.edu   
Sponsors and Collaborators
University of Michigan
National Institute of Dental and Craniofacial Research (NIDCR)
Investigators
Principal Investigator: Alexandre F DaSilva, DDS, DMedSc University of Michigan

Responsible Party: Alexandre DaSilva, DDS, MS, Associate Professor, BMS-Prosthodontics Dept., School of Dentistry, University of Michigan
ClinicalTrials.gov Identifier: NCT03724032     History of Changes
Other Study ID Numbers: HUM00110179
U01DE025633 ( U.S. NIH Grant/Contract )
First Posted: October 30, 2018    Key Record Dates
Last Update Posted: December 17, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes

Additional relevant MeSH terms:
Temporomandibular Joint Disorders
Temporomandibular Joint Dysfunction Syndrome
Craniomandibular Disorders
Mandibular Diseases
Jaw Diseases
Musculoskeletal Diseases
Joint Diseases
Muscular Diseases
Stomatognathic Diseases
Myofascial Pain Syndromes