Kappa Opioid Receptor Antagonism for the Tx of AUD and Comorbid PTSD
Condition: Post Traumatic Stress Disorder; Alcohol Abuse
MeSH terms: Alcoholism; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Intervention: 2mg Buprenex and 380mg Vivitrol; Placebo (SL pill qd, IM injection q4weeks)
Intervention description: Daily 2mg SL BUP (84 pills total, taken sublingual every day for 12 weeks) and Q4wks (given intramuscular, 3 injections total: at baseline, week4 and week8 ) IM NLTRX; Daily SL placebo (84 pills total, taken sublingual every day for 12 weeks) and Q4wks (given intramuscular, 3 injections total: at baseline, week4 and week8) IM Placebo
Intervention MeSH terms: Naltrexone; Buprenorphine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: proof-of-concept study
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking description: To minimize bias, a placebo drug is employed as the comparison group to active study drug and the study is conducted in a double-masked fashion in that both the participants and the Independent Assessors who are assessing study outcomes are masked to treatment assignment. The only individuals at the site with access to treatment assignment information are the research pharmacists.
Enrollment: 69.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Alcohol Use Disorder (AUD); Alcoholism; Alcohol Abuse; Post Traumatic Stress Disorder (PTSD)

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 alcohol use disorder of comorbid (AUD) and post-traumatic stress disorder
      (PTSD)
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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).

          2. Current moderate to severe AUD as determined by MINI International Neuropsychiatric
             Interview for DSM-5 (MINI-5).

          3. 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.

          4. PTSD diagnosis defined by MINI-5 at screening.

          5. Clinician Administered PTSD Scale for DSM-5 (CAPS-5) total score ≥26 for the past week
             at baseline.

          6. 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.

          7. Must have a CIWA-Ar score of < 8 prior to randomization.

          8. Willing and able to refrain from medications thought to influence alcohol consumption
             (other formulations of naltrexone, disulfiram, acamprosate, topiramate, ondansetron,
             and baclofen).

          9. 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 Criteria:

          1. Current diagnosis of DSM-5 bipolar I, schizophrenia, schizoaffective, and/or major
             depressive disorder with psychotic features (defined by MINI-5 at screening).

          2. 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).

          3. 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.

          4. Current diagnosis of severe non-alcohol substance use disorder (except for caffeine
             and nicotine) during the preceding 1 month, based on participant screening interview.

          5. Use of opioids within 2 weeks of baseline or opioid use disorder in the previous 90
             days.

          6. History of severe traumatic brain injury (TBI) per Ohio State University TBI
             Identification Method. Note: history of mild or moderate TBI is allowed.

          7. 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.

          8. 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.

          9. History of allergic reaction, bronchospasm or hypersensitivity to a naltrexone or
             buprenorphine.

         10. Unable or unwilling to refrain from medications thought to influence alcohol
             consumption (see inclusion criteria above.)

         11. 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.

         12. Persons who are imprisoned, of minor age, diagnosed with dementia, diagnosed with a
             terminal illness, or otherwise require a surrogate to provide informed consent.