ACTION: Trial of Adding Buprenorphine, CBT, and TMS to Improve Outcomes of Long-Term Opioid Therapy for Chronic Pain

NCT06442566 | Recruiting Phase 1 FDA Drug FDA Device

• 2 other identifiers: Pro001301231R01DA058620
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Buprenorphine Tolerability

  Tolerability of open-label transdermal buprenorphine. Buprenorphine tolerability defined as the proportion of patients who do not discontinue buprenorphine due to adverse effects or intolerance.

  up to Day-13

• Pain Severity -with Buprenorphine Patch

  Pain severity is measured by the Brief Pain Inventory (BPI) Severity Scale and is typically scored as the mean of the four severity items ("average," "worst," "usual," "now," range 0-10) with a higher score being worse.

  up to Day-20

Secondary Outcomes (2)

• Buprenorphine Transition Rate

  Day-20

• Quality of Life -with Buprenorphine Patch

  up to Day-20

Study Arms (3)

open label BUP

EXPERIMENTAL

Drug: Buprenorphine Patch

Real vs Placebo BUP

ACTIVE COMPARATOR

Drug: Buprenorphine Patch; Drug: Placebo

Real vs Sham TMS

ACTIVE COMPARATOR

Device: Transcranial Magnetic Stimulation (TMS); Device: Sham Transcranial Magnetic Stimulation (TMS)

Interventions

Buprenorphine Patch DRUG

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

Real vs Placebo BUP; open label BUP

Placebo DRUG

double-blinded randomization to placebo or transdermal buprenorphine

Real vs Placebo BUP

Transcranial Magnetic Stimulation (TMS) DEVICE

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

Real vs Sham TMS

Sham Transcranial Magnetic Stimulation (TMS) DEVICE

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

Real vs Sham TMS

Eligibility Criteria

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

You may qualify if:

• 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:
• Taking benzodiazepines with opioids
• Substance Use Disorder diagnosis \[non-tobacco; Opioid Risk Tool\]
• \) 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 \[self-report\]
• Dizziness and/or falls
• Difficult-to-manage stomach pain, nausea, constipation or GI issues
• Fatigue or low energy
• Sleepiness or sedation

You may not qualify if:

• Known allergy to buprenorphine
• Active moderate or severe substance use disorder with the exception of those listed below:
• Those with nicotine use disorder.
• 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).

Sponsors & Collaborators

• Medical University of South Carolina: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29407, United States

RECRUITING

MeSH Terms

Conditions

Chronic Pain

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Kelly Barth

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kelly Barth

CONTACT

843-792-0686; stephen@musc.edu

Rafael Mendoza

CONTACT

mendozra@musc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Arm 1 open label, double blind procedures for randomization of BUP and TMS
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor-Faculty

Model Details: SMART

Study Record Dates

• First Submitted: May 29, 2024
• First Posted: June 4, 2024
• Study Start: August 12, 2024
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: November 5, 2025

Record last verified: 2025-11

Locations

US (1)