Opioid Withdrawal, Chronic Pain
Conditions
Keywords
opioids, long-term opioid use, chronic pain, TMS
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.
Interventions
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
DRUGPlacebo
double-blinded randomization to placebo or transdermal buprenorphine
DEVICETranscranial Magnetic Stimulation (TMS)
double-blinded randomization to REAL intermittent theta burst (iTBS) rTMS
double-blinded randomization to SHAM intermittent theta burst (iTBS) rTMS
Sponsors
National Institute on Drug Abuse (NIDA)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Arm 1 open label, double blind procedures for randomization of BUP and TMS
Intervention model description
SMART
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Buprenorphine Tolerability | up to Day-13 | 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. |
| Pain Severity -with Buprenorphine Patch | 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, usual, now, range 0-10) with a higher score being worse. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Buprenorphine Transition Rate | Day-20 | Buprenorphine transition rate defined as the proportion of participants who spontaneously elect to continue buprenorphine after Phase I. |
| Quality of Life -with Buprenorphine Patch | 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. |
Countries
United States
Contacts
Primary ContactKelly Barth
Backup ContactRafael Mendoza
Outcome results
None listed