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Protocol Details

Spironolactone in Alcohol Use Disorder (SAUD): A Double-Blind, Placebo-Controlled, Ascending Dose, Phase 1b Study

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

001546-DA

Sponsoring Institute

National Institute on Drug Abuse (NIDA)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 21 Years
Max Age: 99 Years

Referral Letter Required

No

Population Exclusion(s)

Non-English Speaking;
Adults who are or may become unable to consent;
Pregnant Women;
Children

Keywords

Alcohol Consumption;
Alcohol Problems;
Alcohol Use Disorder;
SPIRONOLACTONE;
Mineralocorticoid Receptor

Recruitment Keyword(s)

None

Condition(s)

Alcohol Use Disorder

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

Other: Placebo
Drug: Spironolactone

Supporting Site

National Institute on Drug Abuse

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.

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Eligibility

INCLUSION CRITERIA:

In order to be eligible to enroll in this study, an individual must meet all of the following criteria:

1. At least 21 years old

2. 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))

3. Self-reported drinking, according to alcohol TimeLine Follow Back (TLFB)

a. at least five days with >= 4 drinks for females or >= 5 drinks for males AND

b. on average more than 1 drink per day for females or more than 2 drinks per day for males during the 28-day period prior to screening

4. Most recent Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-Ar) score is < 10

5. Able to speak, read, write, and understand English as demonstrated by their ability to understand and sign the consent for the NIDA screening protocol.

6.Female participants must be postmenopausal for at least one year, surgically sterile, or practicing an effective method of birth control before entry and throughout the study and must have a negative urine pregnancy test at each visit. Examples of birth control methods include (but are not limited to) oral contraceptives or Norplant , barrier methods such as diaphragms with contraceptive jelly, cervical caps with contraceptive jelly, condoms, intrauterine devices, a partner with a vasectomy, or abstinence from intercourse.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. 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 %

2. Clinically significant and/or symptomatic hyponatremia, hypomagnesemia, hypocalcemia, and hyperuricemia based on Medical Advisory Investigators (MAI) or designee judgment.

3. Known history of clinically significant orthostatic hypotension

4. Known history of hypoaldosteronism, hyperaldosteronism, Addison s disease

5. Diagnosis of NYHA class III-IV heart failure, or unstable cardiovascular conditions (e.g., arrhythmias, clinically significant ECG abnormalities)

6. 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

7. Current use of MR antagonists

8. Current use of FDA-approved pharmacotherapy for AUD, or seeking treatment for AUD

9. Known history of prior hypersensitivity reaction to spironolactone or other MR antagonists, or any of the product components

10. Known history of alcohol withdrawal seizure and delirium tremens.

11. 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.

12. Pregnancy, intention to become pregnant, or breastfeeding.

13. Any other reason or clinical condition that the Investigators judge would interfere with study participation and/or be unsafe for a participant


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Citations:

L(SqrRoot)(Copyright)k(SqrRoot)>= AH, McGinn MA, Farokhnia M. The Mineralocorticoid Receptor: An Emerging Pharmacotherapeutic Target for Alcohol Use Disorder? ACS Chem Neurosci. 2022 Jul 6;13(13):1832-1834. doi: 10.1021/acschemneuro.2c00326. Epub 2022 Jun 24. PMID: 35748762.

Farokhnia M, Rentsch CT, Chuong V, McGinn MA, Elvig SK, Douglass EA, Gonzalez LA, Sanfilippo JE, Marchette RCN, Tunstall BJ, Fiellin DA, Koob GF, Justice AC, Leggio L, Vendruscolo LF. Spironolactone as a potential new pharmacotherapy for alcohol use disorder: convergent evidence from rodent and human studies. Mol Psychiatry. 2022 Nov;27(11):4642-4652. doi: 10.1038/s41380-022-01736-y. Epub 2022 Sep 20. PMID: 36123420.

Palzes VA, Farokhnia M, Kline-Simon AH, Elson J, Sterling S, Leggio L, Weisner C, Chi FW. Effectiveness of spironolactone dispensation in reducing weekly alcohol use: a retrospective high-dimensional propensity score-matched cohort study. Neuropsychopharmacology. 2021 Nov;46(12):2140-2147. doi: 10.1038/s41386-021-01117-z. Epub 2021 Aug 2. PMID: 34341493; PMCID: PMC8505557.

Aoun EG, Jimenez VA, Vendruscolo LF, Walter NAR, Barbier E, Ferrulli A, Haass-Koffler CL, Darakjian P, Lee MR, Addolorato G, Heilig M, Hitzemann R, Koob GF, Grant KA, Leggio L. A relationship between the aldosterone-mineralocorticoid receptor pathway and alcohol drinking: preliminary translational findings across rats, monkeys and humans. Mol Psychiatry. 2018 Jun;23(6):1466-1473. doi: 10.1038/mp.2017.97. Epub 2017 May 2. PMID: 28461696; PMCID: PMC5668213.

Leggio L, Ferrulli A, Cardone S, Miceli A, Kenna GA, Gasbarrini G, Swift RM, Addolorato G. Renin and aldosterone but not the natriuretic peptide correlate with obsessive craving in medium-term abstinent alcohol-dependent patients: a longitudinal study. Alcohol. 2008 Aug;42(5):375-81. doi: 10.1016/j.alcohol.2008.03.128. Epub 2008 May 16. PMID: 18486430.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Lorenzo Leggio, M.D.
National Institute on Drug Abuse (NIDA)
NIH BIOMEDICAL RESEARCH CENTER BG RM 04A515
251 BAYVIEW BLVD.
BALTIMORE MD 21224
(240) 478-1503
lorenzo.leggio@nih.gov

NIDA IRP Screening Team
National Institute on Drug Abuse (NIDA)

(800) 535-8254
researchstudies@nida.nih.gov

NIDA IRP Screening Team

(800) 535-8254
researchstudies@nida.nih.gov

Clinical Trials Number:

NCT05807139

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