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

NCT ID: NCT06442566

Last Updated: 2025-11-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-12
• Study Completion Date: 2029-03-31

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.

Detailed Description

With little evidence available to guide the provision of clinical care for patients on long-term opioid therapy (LTOT) in whom the risks outweigh the benefits, major questions remain about optimizing the risk/benefit profile of LTOT, including: how to best engage patients voluntarily in this process; the safety, tolerability and effectiveness of newer treatment approaches; and optimal treatment selection. The primary objective of the proposed study is to begin to systematically address gaps in this important area to improve pain, reduce risk, and improve quality of life for individuals on LTOT.

Conditions

Opioid Withdrawal; Chronic Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Real vs Sham TMS

Group Type: ACTIVE_COMPARATOR

Transcranial Magnetic Stimulation (TMS)

Intervention Type: DEVICE

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

Sham Transcranial Magnetic Stimulation (TMS)

Intervention Type: DEVICE

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

open label BUP

Group Type: EXPERIMENTAL

Buprenorphine Patch

Intervention Type: 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

Group Type: ACTIVE_COMPARATOR

Buprenorphine Patch

Intervention Type: 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

Placebo

Intervention Type: DRUG

double-blinded randomization to placebo or transdermal buprenorphine

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

Intervention Type: DRUG

Placebo

double-blinded randomization to placebo or transdermal buprenorphine

Intervention Type: DRUG

Transcranial Magnetic Stimulation (TMS)

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

Intervention Type: DEVICE

Sham Transcranial Magnetic Stimulation (TMS)

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

Intervention Type: DEVICE

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Kelly Barth

Professor-Faculty

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kelly Barth

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Kelly Barth

Role: CONTACT

stephen@musc.edu

843-792-0686

Rafael Mendoza

Role: CONTACT

mendozra@musc.edu

Facility Contacts

Kelly Barth

Role: primary

stephen@musc.edu

Rafael Mendoza

Role: backup

mendozra@musc.edu

Other Identifiers

1R01DA058620

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00130123

Identifier Type: -

Identifier Source: org_study_id