ACTION: Trial of Adding Buprenorphine, CBT, and TMS to Improve Outcomes of Long-Term Opioid Therapy for Chronic Pain (ACTION)
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.
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
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.
Study Type
Study Type
Enrollment (Estimated)
Enrollment
Phase
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
Study Contact
- Name: Kelly Barth
- Phone Number: 843-792-0686
- Email: stephen@musc.edu
Study Contact Backup
- Name: Rafael Mendoza
- Email: mendozra@musc.edu
Study Locations
-
-
South Carolina
-
Charleston, South Carolina, United States, 29407
- Recruiting
- Medical University of South Carolina
-
Contact:
- Rafael Mendoza
- Email: mendozra@musc.edu
-
Contact:
- Kelly Barth
- Email: stephen@musc.edu
-
Principal Investigator:
- Kelly Barth
-
-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria:
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
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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: Double
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Experimental: open label BUP
|
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 |
|
Active Comparator: Real vs Placebo BUP
|
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 double-blinded randomization to placebo or transdermal buprenorphine |
|
Active Comparator: Real vs Sham TMS
|
double-blinded randomization to REAL intermittent theta burst (iTBS) rTMS double-blinded randomization to SHAM intermittent theta burst (iTBS) rTMS |
What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Intervention Tolerability
Time Frame: up to Day-13
|
(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 |
up to Day-13
|
|
Pain Severity
Time Frame: up to Day-20
|
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. |
up to Day-20
|
Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Buprenorphine Transition Rate
Time Frame: Day-20
|
Buprenorphine transition rate defined as the proportion of participants who spontaneously elect to continue buprenorphine after Phase I. |
Day-20
|
|
Quality of Life
Time Frame: up to Day-20
|
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. |
up to Day-20
|
|
Pain Interference
Time Frame: up to Day-20
|
BPI Interference Scale (lowest score 0, highest 40; higher worse) |
up to Day-20
|
|
Pain Catastrophizing
Time Frame: up to Day-20
|
Pain Catastrophizing Scale SF 6 (lowest score 0, highest score 24; higher worse) |
up to Day-20
|
|
Patient Global Impression of Change
Time Frame: up to Day-20
|
range 1-7, higher worse |
up to Day-20
|
|
Opioid misuse risk
Time Frame: up to Day-20
|
Current opioid Misuse Measure (COMM |
up to Day-20
|
Collaborators and Investigators
Sponsor
Sponsor
Collaborators
Collaborators
Investigators
Investigators
- Principal Investigator: Kelly Barth, Medical University of South Carolina
Study record dates
Study Major Dates
Study Start (Actual)
Study Start
Primary Completion (Estimated)
Primary Completion
Study Completion (Estimated)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
Other Study ID Numbers
- Pro00130123
- 1R01DA058620 (U.S. NIH Grant/Contract)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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