Status:

TERMINATED

Kappa Opioid Receptor Antagonism for the Tx of AUD and Comorbid PTSD

Lead Sponsor:

Pharmacotherapies for Alcohol and Substance Use Disorders Alliance

Collaborating Sponsors:

United States Department of Defense

RTI International

Conditions:

Post Traumatic Stress Disorder

Alcohol Abuse

Eligibility:

All Genders

18-70 years

Phase:

PHASE2

Brief Summary

Objective: Evaluate the efficacy and physiological effects of sublingual buprenorphine (SL-BUP; Subutex) combined with extended-release injectable naltrexone (XR-NTX; Vivitrol) in the treatment alcoho...

Detailed Description

Hypothesis: The treatment of (sublingual buprenorphine) SL-BUP + (extended release naltrexone) XR-NTX will significantly reduce both (alcohol use disorder) AUD and (post-traumatic stress disorder) PTS...

Eligibility Criteria

Inclusion

  • Male or female, 18 to 70 years of age, capable of reading and understanding English, and able to provide written informed consent (i.e. no surrogate).
  • Current moderate to severe AUD as determined by MINI International Neuropsychiatric Interview for DSM-5 (MINI-5).
  • At least two recent episodes of heavy drinking (\>5 standard drinks/sessions for men and \>4 standard drinks/sessions for women) over the past 30 days, and heavy drinking pattern defined as 14 drinks per week for women and 21 drinks per week for men for at least 2 of a 4-week interval within the 90 days prior to baseline; i.e. at least Moderate Risk level on WHO category.
  • PTSD diagnosis defined by MINI-5 at screening.
  • Clinician Administered PTSD Scale for DSM-5 (CAPS-5) total score ≥26 for the past week at baseline.
  • Females of child-bearing potential must be using medically acceptable birth control (e.g. oral, implantable, injectable, or transdermal contraceptives; intrauterine device; double-barrier method) AND not be pregnant OR have plans for pregnancy or breastfeeding during the study.
  • Must have a CIWA-Ar score of \< 8 prior to randomization.
  • Willing and able to refrain from medications thought to influence alcohol consumption (other formulations of naltrexone, disulfiram, acamprosate, topiramate, ondansetron, and baclofen).
  • Willing and able to refrain from psychotropic medications: stimulants/ADHD treatment, Alzheimer's medications, antipsychotics, benzodiazepines, antianxiety medications, mood stabilizers, and other sedatives.
  • Notes:
  • Participants may continue stable dose of antidepressants, prazosin, and non-benzodiazepine hypnotics and non-benzodiazepine anxiolytics to treat PTSD or insomnia.
  • Stable dose is defined as taken for ≥2 months prior to randomization and current does has been stable for ≥3 weeks prior to randomization and held constant during 12 weeks of study medication.)

Exclusion

  • Current diagnosis of DSM-5 bipolar I, schizophrenia, schizoaffective, and/or major depressive disorder with psychotic features (defined by MINI-5 at screening).
  • Increased risk of suicide that necessitates inpatient treatment or warrants therapy excluded by the protocol, and/or current suicidal plan, per investigator clinical judgement, based on interview and defined on the Columbia Suicidality Severity Rating Scale (C-SSRS).
  • Treatment with trauma-focused therapy for PTSD (e.g. Cognitive Processing Therapy, Prolonged Exposure, or EMDR) within two weeks of baseline study visit. Note: Supportive psychotherapy in process for PTSD at time of Screening may be continued.
  • Current diagnosis of severe non-alcohol substance use disorder (except for caffeine and nicotine) during the preceding 1 month, based on participant screening interview.
  • Use of opioids within 2 weeks of baseline or opioid use disorder in the previous 90 days.
  • History of severe traumatic brain injury (TBI) per Ohio State University TBI Identification Method. Note: history of mild or moderate TBI is allowed.
  • Any clinically significant, uncontrolled, or medical/surgical condition that would contraindicate use of SL-BUP + XR-NTX, or limit ability to complete study assessments, including seizures (other than childhood febrile seizures), severe renal insufficiency, significant arrhythmia or heart block, heart failure, or myocardial infarction within the past 2 years, severe thrombocytopenia or hemophilia, severe hepatic failure, complete hearing loss, and/or need for surgery that might interfere with ability to participate.
  • Clinically significant laboratory abnormalities, including a thyroid stimulating hormone (TSH) \>1.5 times upper limit of normal, hyperthyroidism, and aspartate aminotransferase and/or alanine aminotransferase \> 3 times upper limit of normal; cardiovascular findings QTcF \>500 msec on electrocardiogram (ECG) or blood pressure \>190/110.
  • History of allergic reaction, bronchospasm or hypersensitivity to a naltrexone or buprenorphine.
  • Unable or unwilling to refrain from medications thought to influence alcohol consumption (see inclusion criteria above.)
  • Unable or unwilling to refrain from psychotropic medications (see inclusion criteria above); with the exception of stable doses of antidepressants, prazosin, and non-benzodiazepine hypnotics and non-benzodiazepine anxiolytics to treat PTSD or insomnia.
  • Persons who are imprisoned, of minor age, diagnosed with dementia, diagnosed with a terminal illness, or otherwise require a surrogate to provide informed consent.

Key Trial Info

Start Date :

May 20 2019

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

January 30 2023

Estimated Enrollment :

69 Patients enrolled

Trial Details

Trial ID

NCT03852628

Start Date

May 20 2019

End Date

January 30 2023

Last Update

September 14 2023

Active Locations (2)

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Page 1 of 1 (2 locations)

1

Tuscaloosa VA Medical Center

Tuscaloosa, Alabama, United States, 35404

2

VA Connecticut Healthcare System

West Haven, Connecticut, United States, 06516