Spironolactone in Alcohol Use Disorder (SAUD)
ConditionAlcohol Use Disorder
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age21-99
SponsorNational Institute on Drug Abuse (NIDA)
About this trial
Background:
Alcohol use disorder (AUD) affects about 29.5 million people in the United States. Only 3 medicines have been approved by Food and Drug Administration to treat AUD. Researchers want to find better treatments for AUD. Animal studies found that a medicine called spironolactone, may decrease the amount of alcohol the animals drank. Spironolactone is approved to treat high blood pressure, or heart failure in people. It is not approved to treat AUD.
Objective:
To test a medicine (spironolactone) in people who sometimes drink excessive alcohol in order to understand how the body breaks down spironolactone and if there are any side effects in people who drink alcohol while taking this medicine.
Eligibility:
People aged 21 and older with AUD.
Design:
Participants will have 4 separate 7-day stays at a clinic in Baltimore over 2 months. Spironolactone is a capsule you swallow. Participants will take a capsule twice a day for 5 days during each clinic stay. During 1 of their 4 stays, they will take a placebo instead of the medicine. The placebo capsule looks just like the spironolactone capsule but contains no medicine. Participants will not know when they are taking the medicine or the placebo.
Participants will not drink alcohol until day 6 of each clinic stay. Then they will be asked to drink alcohol in a bar-like area in the clinic. Their breath and blood alcohol levels and their well-being will be measured.
Participants will undergo other tests in the clinic:
A DEXA (dual energy X-ray absorptiometry) scan uses X-rays to measure bone density and muscle mass. Participants will lie on an open-top, padded table, then a small arm will scan the full length of their body. The radiation participants will get in this study is about the same as from one regular x-ray.
Blood tests. Participants may feel some discomfort at the site of needle entry.
Electrocardiogram. This test records the heart activity. Sensors are attached to the skin with stickers and removed after a few minutes.
Urine tests. All urine will be collected over a 3-day period during each stay. We will measure the amount of urine, and different hormones and salts in the urine.
Questionnaires and tasks. Participants will answer questions about their alcohol use. They will perform tasks to test mood, craving, mental and physical coordination, and how much they feel an effect from alcohol after drinking.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
At least 21 years old
Alcohol Use Disorder (minimum 2 symptoms on a validated diagnostic tool, e.g., the Mini- International Neuropsychiatric Interview (MINI) or the Structured Clinical Interview for DSM Disorders (SCID))
At least four days with >= 4 drinks for females or >= 5 drinks for males during the 28-day period prior to screening, according to alcohol TimeLine Follow Back (TLFB)
Most recent Clinical Institute Withdrawal Assessment for Alcohol - revised (CIWA-Ar) score is < 10
Disqualifiers
Most recent blood tests: potassium > 5.2 mmol/L; creatinine >= 2 mg/dL; eGFR < 60 mL/min/1.73 m², hemoglobin A1c (HbA1c) > 6.5 %
Clinically significant and/or symptomatic hyponatremia, hypomagnesemia, hypocalcemia, and hyperuricemia based on Medical Advisory Investigators (MAI) or designee judgment.
Known history of clinically significant orthostatic hypotension
Known history of hypoaldosteronism, hyperaldosteronism, Addison s disease
Trial design
Design model
Crossover
Treatments tested in this trial
Placebo
Other interventionPlacebo
Spironolactone
DrugSpironolactone and its matched placebo will be encapsulated into hard gelatin capsules, in same color, size and taste, to allow blinding. Participants will receive 2x50 mg/day, 2x100 mg, and 2x200 mg/day in three sessions (Stages); these Visits always occur in ascending order of dosage. In the remaining session, participants receive the placebo. Spironolactone is approved by the FDA, commercially available, and used in clinical practice for the treatment of hypertension, NYHA Class III-IV heart failure, edema in cirrhotic patients, and primary hyperaldosteronism. Comprehensive information about spironolactone, including its pharmacological properties, are provided in the Prescribing Information.
Treatment groups
20 Participants
are divided into 4 treatment groupsGroup A: Placebo 1st visitExperimental treatment 2 interventions
Group B: Placebo 2nd visitExperimental treatment 2 interventions
Group C: Placebo 3rd visitExperimental treatment 2 interventions
Group D: Placebo 4th visitExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Describe steady-state PK of spironolactone in individuals with AUD, before and after oral alcohol administration.
PK characteristics of spironolactone (e.g., total concentration, peak concentration, elimination half-life) before (day 5) and after (day 6) oral alcohol administration.
Time frame
Before and after oral alcohol administration.2
Describe alcohol PK during concomitant spironolactone use
PK characteristics of alcohol (e.g., blood alcohol concentrations, time for elimination) during concomitant spironolactone treatment (0, 100, 200, and 400 mg/day)
Time frame
12 hours after oral alcohol administrationSecondary outcomes
1
Determine whether spironolactone alters subjective and cognitive effects of acute alcohol administration
Subjective response to alcohol (e.g., sedation, stimulation, mood) and cognitive performance (e.g., psychomotor function, attention) under alcohol administration, during concomitant spironolactone treatment (0, 100, 200, and 400 mg/day)
Time frame
12 hours after oral alcohol administration2
Determine safety, tolerability, and potential drug-alcohol interaction by administering spironolactone, combined with alcohol, in individuals with AUD
Number and intensity of adverse events (AEs) experienced under different spironolactone doses (0, 100, 200, 400 mg/day)
Time frame
12 hours after oral alcohol administration3
Describe steady-state PK of spironolactone metabolites in individuals with AUD, before and after alcohol administration
PK characteristics (e.g., total concentration, peak concentration, elimination half-life) of spironolactone metabolites; canrenone, TMS, HTMS, before (day 5) and after (day 6) alcohol administration.
Time frame
Before and after oral administration of alcohol.Sponsors and contacts
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Source ClinicalTrials.gov