Spironolactone in Alcohol Use Disorder (SAUD): A Double-Blind, Placebo-Controlled, Ascending Dose, Phase 1b Study
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Describe steady-state PK of spironolactone in individuals with AUD, before and after oral alcohol administration.
研究概览
简要总结
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.
详细描述
Study Description:
This study will examine pharmacokinetic (PK) and pharmacodynamic (PD) parameters of spironolactone and alcohol, during concomitant oral administration (0, 100, 200, 400 mg/day spironolactone PO), and test the safety and tolerability of spironolactone, co-administered with alcohol, in individuals with alcohol use disorder (AUD).
Objectives:
Our objective is to assess PK and PD parameters during spironolactone-alcohol co-administration, in individuals with AUD. We will also test the safety, tolerability, and potential drug-alcohol interaction.
Endpoints:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 21 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •In order to be eligible to enroll in this study, an individual must meet all of the following criteria:
- •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
- •Able to speak, read, write, and understand English as demonstrated by their ability to understand and sign the consent for the NIDA screening protocol.
- •Female participants must be postmenopausal for at least one year, surgically sterile, or practicing a highly effective method of birth control before entry and throughout the study and must have negative pregnancy tests at each stage. Examples of highly effective methods of birth control include abstinence, hormonal contraceptives (e.g., certain birth control pills, contraceptive patch, vaginal ring, or implants), intrauterine device (IUD), tubal ligation, or vasectomy.
排除标准
- •An individual who meets any of the following criteria will be excluded from participation in this study:
- •Most recent blood tests: potassium > 5.2 mmol/L; creatinine >= 2 mg/dL; eGFR < 60 mL/min/1.73 m^2, 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
- •Diagnosis of NYHA class III-IV heart failure, or unstable cardiovascular conditions (e.g., arrhythmias, clinically significant ECG abnormalities)
- •Current use of any diuretic, angiotensin receptor blocker (ARB), angiotensin converting enzyme inhibitor (ACEI), potassium supplementation, potassium containing salt substitute, heparin and low molecular weight heparin (LMWH), trimethoprim, lithium, digoxin, cholestyramine
- •Current use of MR antagonists
- •Current use of FDA-approved pharmacotherapy for AUD, or seeking treatment for AUD
- •Known history of prior hypersensitivity reaction to spironolactone or other MR antagonists, or any of the product components
- •Known history of alcohol withdrawal seizure and delirium tremens.
- •Physical and/or mental health conditions that are clinically unstable, as determined by the study clinicians, including (but not limited to) major depressive disorder or generalized anxiety disorder unstable during the past three months or other psychiatric conditions (e.g., schizophrenia, bipolar disorder) unstable during the past twelve months prior to screening.
- •Pregnancy, intention to become pregnant, or breastfeeding.
- •Any other reason or clinical condition that the Investigators judge would interfere with study participation and/or be unsafe for a participant.
研究组 & 干预措施
Placebo 2nd visit
stage 1: 2x50 mg/day spironolactonestage 2: Placebostage3: 2x100 mg/day spironolactonestage 4: 2x200 mg/day spironolactone
干预措施: Spironolactone (Drug)
Placebo 1st visit
stage 1: Placebostage 2: 2x50 mg/day spironolactonestage 3: 2x100 mg/day spironolactonestage4: 2x200 mg/day spironolactone
干预措施: Spironolactone (Drug)
Placebo 2nd visit
stage 1: 2x50 mg/day spironolactonestage 2: Placebostage3: 2x100 mg/day spironolactonestage 4: 2x200 mg/day spironolactone
干预措施: Placebo (Other)
Placebo 3rd visit
stage1: 2x50 mg/day spironolactonestage 2: 2x100 mg/day spironolactonestage 3: Placebostage4: 2x200 mg/day spironolactone
干预措施: Placebo (Other)
Placebo 4th visit
Stage1: 2x50 mg/day spironolactoneStage 2: 2x100 mg/day spironolactonestage 3: 2x200 mg/day spironolactonestage 4: Placebo
干预措施: Placebo (Other)
Placebo 1st visit
stage 1: Placebostage 2: 2x50 mg/day spironolactonestage 3: 2x100 mg/day spironolactonestage4: 2x200 mg/day spironolactone
干预措施: Placebo (Other)
Placebo 3rd visit
stage1: 2x50 mg/day spironolactonestage 2: 2x100 mg/day spironolactonestage 3: Placebostage4: 2x200 mg/day spironolactone
干预措施: Spironolactone (Drug)
Placebo 4th visit
Stage1: 2x50 mg/day spironolactoneStage 2: 2x100 mg/day spironolactonestage 3: 2x200 mg/day spironolactonestage 4: Placebo
干预措施: Spironolactone (Drug)
结局指标
主要结局
Describe steady-state PK of spironolactone in individuals with AUD, before and after oral alcohol administration.
时间窗: 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.
Describe alcohol PK during concomitant spironolactone use
时间窗: 12 hours after oral alcohol administration
PK characteristics of alcohol (e.g., blood alcohol concentrations, time for elimination) during concomitant spironolactone treatment (0, 100, 200, and 400 mg/day)
次要结局
- Determine whether spironolactone alters subjective and cognitive effects of acute alcohol administration(12 hours after oral alcohol administration)
- Determine safety, tolerability, and potential drug-alcohol interaction by administering spironolactone, combined with alcohol, in individuals with AUD(12 hours after oral alcohol administration)
- Describe steady-state PK of spironolactone metabolites in individuals with AUD, before and after alcohol administration(Before and after oral administration of alcohol.)