Dutasteride Treatment for Reducing Heavy Drinking in AUD: Predictors of Efficacy

• ClinicalTrials.gov Identifier: NCT04098302
• Recruitment Status: Recruiting
• First Posted: September 23, 2019
• Last Update Posted: October 21, 2019
• Sponsor: UConn Health
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Information provided by (Responsible Party): Jonathan Covault, UConn Health

Tracking Information

• First Submitted Date: September 19, 2019
• First Posted Date: September 23, 2019
• Last Update Posted Date: October 21, 2019
• Actual Study Start Date: October 15, 2019
• Estimated Primary Completion Date: May 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 19, 2019)

• Change in Heavy Drinking Days Per Week by Medication Group [ Time Frame: 12 weeks (from initiation to end of treatment phase 1) ]
  Change in the number of heavy drinking days (i.e., four or more drinks in a day for women and five or more drinks in a day for men) during treatment phase of study. Daily drinking data will be aggregated to the weekly level.
• Change in Drinks Per Week by Medication Group [ Time Frame: 12 weeks (from initiation to end of treatment phase 1) ]
  Change in the number of drinks per week during treatment phase of study. Daily drinking data will be aggregated to the weekly level.

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT04098302 on ClinicalTrials.gov Archive Site
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Dutasteride Treatment for Reducing Heavy Drinking in AUD: Predictors of Efficacy
• Official Title: Dutasteride Treatment for Reducing Heavy Drinking in AUD: Predictors of Efficacy
• Brief Summary: The purpose of this study is to evaluate the safety and efficacy of dutasteride in reducing drinking and heavy drinking in men and women with alcohol use disorder. The investigators hypothesize that dutasteride 1 mg per day will be well tolerated in this patient population and that, compared to placebo treatment, dutasteride will result in a greater reduction in drinks per week and in the frequency of heavy drinking days.

Detailed Description

Heavy drinking remains a significant public health problem and is frequently under treated. Although several medications have been shown to help patients stop or reduce drinking, additional medication options are needed as there is considerable variability in effectiveness or tolerability of existing medications for individual patients. Additionally, identification of individual subject level predictors of efficacy are needed to better personalize pharmacotherapy treatment recommendations. This study will seek to replicate and extend our results showing efficacy of a novel medication dutasteride for reducing drinking and will examine potential easily measured predictors of response.

Dutasteride is a widely prescribed medication for benign prostatic hypertrophy and androgenic hair loss that also modulates the elimination of cortisol and the production of some neuroactive steroids. Changes in the regulation of cortisol and neuroactive steroids have each been suggested as factors which may contribute to the maintenance of alcohol dependence. Data from a recently completed first randomized placebo controlled trial of dutasteride for AUD in a sample of male drinkers, indicates that dutasteride is well tolerated in alcoholics and has efficacy in helping subjects reduce drinking. Additionally, results indicate that dutasteride may be particularly helpful for patients who drink to cope with anxiety and negative emotions, a group of patients with poor response to other treatments.

This 24-week treatment study will use an innovative randomized placebo controlled step therapy design to examine the safety and efficacy of dutasteride to reduce drinking by treatment seeking women and men with hazardous levels of alcohol use. At 12-weeks placebo non-responders will transition to dutasteride and dutasteride non-responders will transition to naltrexone, an FDA approved medication with demonstrated efficacy for reducing heavy drinking. 12-week responders (reduction in drinks/week of 60% or greater compared with screening) will continue for an additional 12-weeks on their initial study medication assignment (dutasteride or placebo).

Additionally, the investigators will examine several baseline measures as predictors of dutasteride efficacy, including drinking to cope, anxiety, adverse child events, and perceived life stress as well as stress resilient vs. reactive genotypes of FKBP5 a chaperone protein involved in regulation of glucocorticoid, androgen and progesterone receptor function.

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

The study consists of two 12-week phases, the first being a 12-week parallel-groups comparison of dutasteride and placebo to evaluate the safety and efficacy of dutasteride 1 mg/day in reducing the likelihood of drinking and heavy drinking in treatment-seeking men and women with alcohol use disorder. In the second 12-week phase, responders in phase 1 (defined as a ≥60% reduction in SD/wk for weeks 9-12 compared with screening) will continue on their initial medication assignment, while non-responder subjects treated with placebo in phase 1 will be given dutasteride during phase 2, and non-responder subjects treated with dutasteride in phase 1 will receive naltrexone daily in phase 2. This design maintains double blind conditions in both phases 1 and 2.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

UConn Health Investigational Pharmacy will randomize to dutasteride vs. placebo for phase 1 at baseline

Primary Purpose: Treatment

• Condition: Alcohol Use Disorder

Intervention

• Drug: Dutasteride Capsules
  1 mg/day oral dutasteride (2 x 0.5 mg capsules)
  Other Name: Avodart
• Drug: Placebo Capsules
  Placebo capsules with matching appearance as Dutasteride Capsules
  Other Name: inactive placebo

Study Arms

• Active Comparator: dutasteride
  two 0.5 mg capsules of dutasteride daily
  Intervention: Drug: Dutasteride Capsules
• Placebo Comparator: placebo capsule
  inactive placebo matched in appearance with dutasteride capsules
  Intervention: Drug: Placebo Capsules

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 19, 2019): 190
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 30, 2025
• Estimated Primary Completion Date: May 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• men and women age 35 to 70 yo inclusive
• have an average weekly ethanol consumption of >24 SD for men and >18 for women and at least 2 HDD/wk over the 8 weeks prior to screening
• current DSM-5 AUD
• no evidence of significant cognitive impairment
• for women of child-bearing potential (i.e., no hysterectomy, bilateral oophorectomy, or tubal ligation; or <2 years postmenopausal) must be non-lactating, practicing a reliable method of birth control and agree to continue such throughout the study and for 6 months following participation, and have a negative serum pregnancy test prior to initiation of treatment.

Exclusion Criteria:

• history of serious alcohol withdrawal symptoms (e.g., perceptual distortions, seizures, delirium, or hallucinations)
• subjects who on clinical examination by a physician are deemed to be too severely alcohol dependent to permit them to participate in a pbo-controlled study (e.g., evidence of serious adverse medical or psychiatric effects that are exacerbated by heavy drinking and would, for safety reasons, lead the physician to urge the patient to be totally abstinent and engage in an empirically supported treatment)
• current, clinically significant physical disease or abnormality on the basis of medical history, physical examination, or routine laboratory evaluation, including direct bilirubin more than 2.5 times the upper limit of normal or transaminase elevations 5 times the upper limit of normal (the investigators will not exclude patients with hypertension, diabetes, asthma or other common medical conditions, if these are adequately controlled and the patient has an ongoing relationship with a primary care provider)
• have a serious psychiatric illness on the basis of history or psychiatric examination (i.e., schizophrenia, active clinically significant mood episode of bipolar disorder or major depression, organic mental disorder, current clinically significant eating disorder, or substantial suicide or violence risk)
• have a current DSM-5 diagnosis of moderate drug use disorder (other than caffeine or nicotine dependence)
• currently taking finasteride, dutasteride, medication for treatment of AUD, or chronic use of opioid pain medication
• are considered by the investigators to be an unsuitable candidate for an investigational drug

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 35 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Marcia Lawlor, BS; 860-679-7000; lawlor@uchc.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04098302
• Other Study ID Numbers: 19-147-2; P50AA027055 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Jonathan Covault, UConn Health
• Study Sponsor: UConn Health
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Jonathan Covault, MD, PhD; UConn Health

• PRS Account: UConn Health
• Verification Date: October 2019