NCT03724032

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

Terminated NA Results posted Last updated 15 June 2023

What this trial tests

NA trial testing HD-tDCS* in Temporomandibular Disorder in 15 participants. Terminated before completion.

Timeline

13 December 2018

Primary endpoint
17 January 2022

17 January 2022

Quick facts

Lead sponsor	University of Michigan
Phase	NA
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	15
Start date	13 December 2018
Primary completion	17 January 2022
Estimated completion	17 January 2022
Sites	1 location across United States

Drugs / interventions tested

• HD-tDCS*
• Sham HD-tDCS*

Conditions studied

• Temporomandibular Disorder — all drugs for Temporomandibular Disorder →

Sponsor

University of Michigan

Who can join

Adults 18 to 65, any sex, with Temporomandibular Disorder. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Group	Value	95% CI
TMD Patients Active Group: Active Comparator	-0.5	-0.7 – 0.6
TMD Patients Sham Group: Sham Comparator	-1.6	-5.4 – 2.2

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

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.

Group	Value	95% CI
TMD Patients Active Group: Active Comparator	0	-2.5 – 2.5
TMD Patients Sham Group: Sham Comparator	0.2	-0.7 – 1.0

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). Secondary · Baseline to 4 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 at 4 weeks after completion of HD-tDCS sessions).

Group	Value	95% CI
TMD Patients Active Group: Active Comparator	-4.8	-122.5 – 112.8
TMD Patients Sham Group: Sham Comparator	-2.1	-17.1 – 13.0

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

The difference in µOR BPND levels (a measure of receptor availability) between Baseline PET #1 and PET (#2) in TMD patients (active vs sham treatment groups). The values indicate changes in the availability of mu-opioid receptors (µOR), referred to as the non-displaceable binding potential (BPND), which reflects the density or concentration of available µORs in a particular region of interest in the brain, specifically the left thalamus. These changes are assessed by conducting baseline positron emission tomography (PET) scans prior to treatment and follow-up PET scans one week after the comp

Group	Value	95% CI
TMD Patients Active Group: Active Comparator	0.05	0.03 – 0.07
TMD Patients Sham Group: Sham Comparator	-0.02	-0.2 – 0.2

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. Secondary · Baseline, 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.

Group	Value	95% CI
TMD Patients Active Group: Active Comparator	-2.5	-10.2 – 5.1
TMD Patients Sham Group: Sham Comparator	0.2	-0.6 – 1.1

Difference in µOR BPND Levels at Rest During PET (#1) in Chronic TMD Patients as Compared to Healthy Subjects. Secondary · During PET #1, at rest (5-40 mins after radiotracer injection)

The difference in µOR BPND levels (a measure of receptor availability) at rest (5-40 mins after radiotracer injection) during baseline PET in TMD patients as compared to healthy subjects. The values for each group the availability of mu-opioid receptors (µOR), referred to as the non-displaceable binding potential (BPND), which reflects the density or concentration of available µORs in a particular region of interest in the brain, specifically the left thalamus. It was assessed by conducting baseline positron emission tomography (PET) scans. The outcome measure 6 was taken during an early-rest

Group	Value	95% CI
TMD Patients Active Group: Active Comparator	1.8	0.7 – 2.9
TMD Patients Sham Group: Sham Comparator	1.5	1.3 – 1.8
Healthy Control Group	1.5	1.4 – 1.6

Difference in µOR BPND Levels During Experimental Sustained Masseteric Pain Stress Challenge During PET (#1) in Chronic TMD Patients as Compared to Healthy Subjects Secondary · PET (#1) during experimental sustained masseteric pain stress challenge (45-90 mins after radiotracer injection)

Difference in µOR BPND levels (a measure of receptor availability) at experimental sustained masseteric pain stress challenge (45-90 mins after radiotracer injection) during baseline PET in TMD patients as compared to healthy subjects. The values for each group the availability of mu-opioid receptors (µOR), referred to as the non-displaceable binding potential (BPND), which reflects the density or concentration of available µORs in a particular region of interest in the brain, specifically the left thalamus. It was assessed by conducting baseline positron emission tomography (PET) scans. The

Group	Value	95% CI
TMD Patients Active Group: Active Comparator	1.7	0.5 – 2.9
TMD Patients Sham Group: Sham Comparator	1.5	1.2 – 1.8
Healthy Control Group	1.5	1.4 – 1.6

Adverse events — posted to ClinicalTrials.gov

Time frame: During the 2-weeks of HD-tDCS treatment. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Active TMD Patients

Serious: 0/4 (0%)

Deaths: 0/4

Sham TMD Patients

Serious: 0/4 (0%)

Deaths: 0/4

Healthy Volunteers

Serious: 0/15 (0%)

Deaths: 0/15

Other adverse events (5 terms — click to expand)

Reaction	System	Active TMD Patients	Sham TMD Patients	Healthy Volunteers
Headache	Investigations	—	—	—
Tingling	Investigations	—	—	—
Scalp Pain	Investigations	—	—	—
sleepiness	Investigations	—	—	—
Scalp Burn sensation (mild)	Investigations	—	—	—

Data from ClinicalTrials.gov NCT03724032 adverse events section.

Sponsor's own description

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).

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Exploring HD-tDCS Effect on μ-opioid Receptor and Pain Sensitivity in Temporomandibular Disorder: A Pilot Randomized Clinical Trial Study.
   Kim DJ, Nascimento TD, Lim M, Danciu T, et al · · 2024 · cited 11× · PMID 37956741 · DOI 10.1016/j.jpain.2023.11.001