Recruiting
Phase 1
Phase 2

rTMS, CBI, Buprenorphine

Sponsor:

Medical University of South Carolina

Code:

NCT06442566

Conditions

Opioid Withdrawal

Chronic Pain

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Accepted

Interventions

Buprenorphine Patch

Placebo

Transcranial Magnetic Stimulation (TMS)

Sham Transcranial Magnetic Stimulation (TMS)

Study Details

Brief summary:

This study will sequentially evaluate three novel and scalable interventions for at-risk individuals on long term opioid therapy for chronic pain: (1) low-dose transdermal buprenorphine initiation without a period of opioid withdrawal; (2) a brief Cognitive Behavioral Intervention for pain (CBI); and (3) "accelerated" rTMS over the left dorsolateral prefrontal cortex, by examining standardized repeated measures of clinical outcomes at baseline, during treatment, and at 4-, 12-, 24- and 52-week follow-up.

Conditions

Opioid Withdrawal

Chronic Pain

Study ID

NCT06442566

Start date

Aug 12, 2024

Status verified date

Nov, 2025

Completion date

Mar 31, 2029

Anticipated

Primary completion date

Mar 31, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Accepted

Inclusion criteria:

Age >/= 18 years

English-speaking

On LTOT, defined as taking daily prescription opioid therapy for 90 days or more

Past week average morphine equivalent dose (MED) >/= 20mg

Willing and able to complete written informed consent

Willing and able to use a mobile/cell phone

Have at least one additional risk for opioid toxicity or overdose from the following list:

Opioid Toxicity or Overdose Risks:

1. Taking benzodiazepines with opioids
2. Substance Use Disorder diagnosis \[non-tobacco; Opioid Risk Tool\]

2\) Having ever experienced an overdose 4) Current major medical problem \[e.g. mod-severe liver disease, pancreatitis, chronic pulmonary disease, untreated sleep apnea, hospitalized for an acute medical issue in the past 6 months\]a,b 5) Response to BPI Item 8 <30%, suggesting less than moderately clinically meaningful response to pain treatmentc 6) Co-morbid psychiatric diagnosis \[Opioid Risk Tool\] 7) Signs of opioid misuse \[any score >0 on the following COMM Items: 3,4,5,9,10,11,14,15,16\] 8)Opioid Risk Tool >3 or Current Opioid Misuse Measure ≥ 9 9) Struggling with any of the following side effects from opioids \[self-report\]

1. Dizziness and/or falls
2. Difficult-to-manage stomach pain, nausea, constipation or GI issues
3. Fatigue or low energy
4. Sleepiness or sedation
5. Trouble with memory or thinking clearly \[COMM Item 1>0\]
6. Other troublesome side effect \[open answer\]

Exclusion criteria:

Known allergy to buprenorphine

Active moderate or severe substance use disorder with the exception of those listed below:

1. . Those with nicotine use disorder.
2. . Those meeting criteria for prescription opioid use disorder using only prescribed opioids will be considered on a case-by-case basis.

Cognitive disorder limiting ability to consent or fully participate in the brief cognitive intervention

Receiving methadone or buprenorphine treatment for OUD or pain

Taking naltrexone

Pregnancy

Currently incarcerated

Taking medications that prolong QTc interval, as determined by study investigators

Personal/immediate family history of Long QT Syndrome.

Significant or unstable condition/s or treatments that may impact safe participation in the study (as determined by the study investigators) such as significant cardiac condition (e.g. poorly-controlled heart failure, current or past cardiac arrhythmia, sustained systolic blood pressure >180), significant metabolic disorder (e.g. labile diabetes, significant electrolyte abnormality), cancer (e.g. brain cancer, chemotherapy-induced cognitive impairment), major psychiatric disorder (e.g. active bipolar disorder, schizophrenia spectrum or other psychotic disorder, suicidal/homicidal intent within the past month, or any suicide attempts within the past year or current active suicidal ideation, as determined by medical clinician), developmental disorder (e.g. autism spectrum disorder, intellectual disability), or other neurologic disease (e.g. movement disorder, multiple sclerosis, moderate to severe brain injury).

Enrolled in a clinical trial or has received an investigational medication or device in the last 30 days.

TMS contraindications (e.g., ferromagnetic implants, conditions or treatments that lower seizure threshold, taking contraindicated medications, no identifiable motor threshold, as determined by study investigators).

Study Design

Enrollment

240 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: open label BUP

active comparator: Real vs Placebo BUP

active comparator: Real vs Sham TMS

Interventions

Buprenorphine Patch

Buprenorphine patch dosing will be individualized based on each participant's current morphine-equivalent dose (per package insert/recommendations; between 5mcg and 20mcg per hour). Dosage based on baseline MEQ (<30 MEQ = 5mcg/hr patch, 30-80 MEQ =10-15mcg/hour patch; >80 MEQ = 20mcg/hour patch), which will remain on for 7 days (Phase Ia Days 1-7), as tolerated

Placebo

double-blinded randomization to placebo or transdermal buprenorphine

Transcranial Magnetic Stimulation (TMS)

double-blinded randomization to REAL intermittent theta burst (iTBS) rTMS

Sham Transcranial Magnetic Stimulation (TMS)

double-blinded randomization to SHAM intermittent theta burst (iTBS) rTMS

Primary outcome measure

  • Buprenorphine Tolerability [ Time Frame: up to Day-13 ]
  • Pain Severity -with Buprenorphine Patch [ Time Frame: up to Day-20 ]

Central Contacts and Locations

Central contacts

Locations

Medical University of South Carolina

Recruiting

Charleston, South Carolina, United States, 29407

Contacts

Kelly Barth

stephen@musc.edu

Rafael Mendoza

mendozra@musc.edu

Principal Investigator:

Kelly Barth

More Information

Sponsor

Medical University of South Carolina

Last update posted

Nov 5, 2025

Last verified

Nov, 2025

Keywords

  • opioids, long-term opioid use, chronic pain, TMS

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Medical University of South Carolina on 2025-11-05.