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Opioid WithdrawalPhase 1/2ACTIONNCT06442566

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

A Phase 1/2 study testing Buprenorphine Patch and Transcranial Magnetic Stimulation (TMS) in people with Opioid Withdrawal and Chronic Pain, run by Medical University of South Carolina at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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"… Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Opioid Withdrawal, Chronic Pain
What is being tested?
Buprenorphine Patch and Transcranial Magnetic Stimulation (TMS)
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
240 participants
Where
1 siteUnited States
Study dates
12 Aug 2024to 31 Mar 2029
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Age >/= 18 years
  • English-speaking
  • On LTOT, defined as taking 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
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  • 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]
  • 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]
  • Dizziness and/or falls
  • Difficult-to-manage stomach pain, nausea, constipation or GI issues
  • Fatigue or low energy
  • Sleepiness or sedation
  • Trouble with memory or thinking clearly [COMM Item 1>0]
  • Other troublesome side effect [open answer]

Who cannot join

  • 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
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  • 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).

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Kelly Barth contact

843-792-0686

stephen@musc.edu

Rafael Mendoza contact

mendozra@musc.edu

United States1 site, 1 recruiting

  • Medical University of South Carolina

    Charleston, South Carolina, 29407

    Kelly Barth, stephen@musc.edu

    Rafael Mendoza, mendozra@musc.edu

    Recruiting

Other trials in United States

About this study

Official title: Sequential Trial of Adding Buprenorphine, Cognitive Behavioral Treatment, and Transcranial Magnetic Stimulation to Improve Outcomes of Long-Term Opioid Therapy for Chronic Pain (ACTION)

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.

Read the 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.

Being tested
Buprenorphine Patch, Placebo, Transcranial Magnetic Stimulation (TMS), Sham Transcranial Magnetic Stimulation (TMS)
Keywords
opioids, chronic pain, TMS, long-term opioid use, buprenorphine, transcranial magnetic stimulation
Medical subject headings
Chronic Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Buprenorphine PatchDrug

    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

  • PlaceboDrug

    double-blinded randomization to placebo or transdermal buprenorphine

  • Transcranial Magnetic Stimulation (TMS)Device

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

  • Sham Transcranial Magnetic Stimulation (TMS)Device

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

Study groups in NCT06442566
Study groupRoleWhat they receive
open label BUPExperimentalNot described
Receives: Drug: Buprenorphine Patch
Real vs Placebo BUPActive comparatorNot described
Receives: Drug: Buprenorphine Patch; Drug: Placebo
Real vs Sham TMSActive comparatorNot described
Receives: Device: Transcranial Magnetic Stimulation (TMS); Device: Sham Transcranial Magnetic Stimulation (TMS)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Intervention Tolerability

    (a) Tolerability of open-label transdermal buprenorphine, defined as the proportion of eligible patients who do not discontinue buprenorphine due to adverse effects, preference, or intolerance. (b) Tolerability of TMS/sham, defined as tolerating 10 sessions of accelerated rTMS

    Measured: up to Day-13

  2. Pain Severity

    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," "least," "now," range 0-10) with a higher score being worse.

    This outcome will be measured after both the buprenorphine vs. placebo trial and the TMS vs. sham trial.

    Measured: up to Day-20

Secondary outcomes (6)

  1. Buprenorphine Transition Rate

    Buprenorphine transition rate defined as the proportion of participants who spontaneously elect to continue buprenorphine after Phase I.

    Measured: Day-20

  2. Quality of Life

    Patient-Reported Outcomes Measurement Information System (PROMIS)-Preference (PROPr) score summarizes multiple domains into a single score anchored at 0 (as bad as dead) and 1 (perfect or ideal health). This score quantifies the value that individuals place on different states of health.

    PROPr is calculated from the scores for the 7 PROMIS domains: Cognition, Depression, Fatigue, Pain Interference, Physical Function, Sleep Disturbance, and Ability to Participate in Social Roles and Activities.

    This outcome will be measured after both the buprenorphine vs. placebo trial and the TMS vs. sham trial.

    Measured: up to Day-20

  3. Pain Interference

    BPI Interference Scale (lowest score 0, highest 40; higher worse)

    Measured: up to Day-20

  4. Pain Catastrophizing

    Pain Catastrophizing Scale SF 6 (lowest score 0, highest score 24; higher worse)

    Measured: up to Day-20

  5. Patient Global Impression of Change

    range 1-7, higher worse

    Measured: up to Day-20

  6. Opioid misuse risk

    Current opioid Misuse Measure (COMM

    Measured: up to Day-20

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jun 2024
  2. Study start12 Aug 2024
  3. Primary completion31 Mar 2028 (estimated)
  4. Study completion31 Mar 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
SMART
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
240 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06442566
Sponsor's protocol ID
Pro00130123
Other IDs
1R01DA058620
Acronym
ACTION
Status last verified
Nov 2026
First submitted
29 May 2024
Last updated
5 Nov 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Buprenorphine Patch and Transcranial Magnetic Stimulation (TMS) in people with Opioid Withdrawal and Chronic Pain, run by Medical University of South Carolina at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Kelly Barth (843-792-0686, stephen@musc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Intervention Tolerability (time frame: up to Day-13). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06442566.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.

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