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

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)

Overview

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.

Interventions

• Drug 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
• Drug Placebo
  double-blinded randomization to placebo or transdermal buprenorphine
• Device Transcranial Magnetic Stimulation (TMS)
  double-blinded randomization to REAL intermittent theta burst (iTBS) rTMS
• Device Sham Transcranial Magnetic Stimulation (TMS)
  double-blinded randomization to SHAM intermittent theta burst (iTBS) rTMS

Primary outcome measures

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

Secondary outcome measures (2)

• Buprenorphine Transition Rate [Time frame: Day-20]
• Quality of Life -with Buprenorphine Patch [Time frame: up to Day-20]

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:

• 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 \[open answer\]

Exclusion criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Sequential

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Medical University of South Carolina — Charleston

Identifiers

NCT: NCT06442566 · Pro00130123 · 1R01DA058620

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗