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

Chronic Pain Clinical Trial

— ACTION  

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06442566
• Other study ID #: Pro00130123
• Secondary ID: 1R01DA058620
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: June 2024
• Est. completion date: March 31, 2029

Study information

• Verified date: May 2024
• Source: Medical University of South Carolina
• Contact: Kelly Barth
• Phone: 843-792-0686
• Email: stephen[@]musc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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" 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 240
• Est. completion date: March 31, 2029
• Est. primary completion date: March 31, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18yrs;
• English-speaking;
• On LTOT, defined as taking daily prescription opioid therapy for 90 days or more;
• Past week average morphine equivalent dose (MED) =50;
• 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:

• Taking benzodiazepines with opioids
• Substance Use Disorder diagnosis [non-tobacco; Opioid Risk Tool]
• Having ever experienced an overdose
• 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]
• Response to Brief Pain Iinventory Item 8 <30%, suggesting less than moderately clinically meaningful response to pain treatment
• Co-morbid psychiatric diagnosis [Opioid Risk Tool]
• Signs of opioid misuse [any score >0 on the following COMM Items: 3, 4, 5, 9, 10, 11, 14, 15, 16]
• Opioid Risk Tool >3 or Current Opioid Misuse Measure = 9
• Struggling with 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 seizure disorder;
• On anti-convulsant medication;
• Known allergy to buprenorphine;
• Active moderate or severe non-opioid substance use disorder (DSMV criteria);
• Active suicidal Ideation;
• Known bipolar disorder;
• Cognitive disorder limiting ability to consent or fully participate in the BCI intervention;
• Severe medical condition (e.g. malignancy), likely to limit life expectancy or study participation;
• Receiving methadone or buprenorphine treatment for OUD or pain;
• On naltrexone;
• Pregnancy;
• Currently Incarcerated;
• Hypokalemia;
• Clinically unstable cardiac or pulmonary disease;
• Taking medications that prolong QTc interval or personal/immediate family history of Long QT Syndrome.

Related Conditions & MeSH terms

• Chronic Pain
• Opioid Withdrawal

Intervention

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
• Placebo
double-blinded randomization to placebo or transdermal buprenorphine

Device:
• Transcranial Magnetic Stimulation (TMS)
double-blinded randomization to REAL intermittent theta burst (iTBS) rTMS
• Sham Transcranial Magnetic Stimulation (TMS)
double-blinded randomization to SHAM intermittent theta burst (iTBS) rTMS

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of South Carolina	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Buprenorphine Transition Rate	Buprenorphine transition rate defined as the proportion of participants who spontaneously elect to continue buprenorphine after Phase I.	Day-20
Secondary	Quality of Life -with Buprenorphine Patch	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.	up to Day-20