Altering Memories That Increase Risk of Relapse in Alcohol Use Disorders

Altering Memories That Increase Risk of Relapse in Alcohol Use Disorders: A Translational Clinical Neuroscience Pilot Investigation of a Novel Pharmacological Agent

The purpose of this study is to examine the effects of rapamycin (sirolimus) versus a placebo, an inactive substance, on responses to alcohol cues in individuals with alcohol use disorder. Rapamycin (sirolimus) is a FDA-approved antibiotic and immunosuppressive drug that is currently used to (a) prevent organ transplant recipients from rejecting their transplants (b) treat cardiovascular diseases, and (c) treat some forms of cancer. Rapamycin (sirolimus) is not FDA-approved to treat alcohol use disorder. The use of rapamycin (sirolimus) in this study is investigational, meaning that the study medication is not a proven treatment for alcohol use disorder. The study will examine the medication's use as a potential treatment for alcohol use disorder, as well as how safe and tolerable it is to take.

Study Overview

• Status: Completed
• Conditions: Alcohol Dependence; Alcohol Use Disorder
• Intervention / Treatment: Drug: Rapamycin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must be treatment-seekers
• Meet criteria for alcohol use disorder
• Must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments
• Must use one of the following methods of birth control: oral contraceptives, barrier methods (diaphragm or condoms with spermicide or both), surgical sterilization, use of an intra-uterine contraceptive device, or complete abstinence from sexual intercourse
• Must live within a 50-mile radius of our research program and have reliable transportation,
• Must consent to remain abstinent from alcohol and all non-prescription drugs prior to medication administration and testing sessions
• Must consent to fast for a two-hour period prior to medication administration
• Must consent to random assignment to the rapamycin vs. placebo conditions.

Exclusion Criteria:

• Cannot be undergoing other alcohol cessation treatment
• Cannot be pregnant, nursing, or of childbearing potential and not using birth control
• Cannot have evidence of or a history of significant endocrine, cardiovascular, pulmonary, renal, or neurological disease
• Cannot have significant liver impairment
• Cannot have an existing infection or immune system disorder
• Cannot have a history of or current psychotic disorder, severe major depression, or bipolar affective disorder
• Cannot currently take anti-arrythmic agents, psychostimulants, or any other agents known to interfere with heart rate and skin conductance monitoring
• Cannot have known or suspected hypersensitivity to macrolide compounds (such as rapamycin/sirolimus)
• Cannot currently take medications that could adversely interact with the study medication, including but not limited to significant inhibitors of CYP2D6 or CYP3A4 (voriconazole, fluconazole, itraconazole, erythromycin, clarithromycin, diltiazem, verapamil, etc.), or significant inducers of CYP3A4, such as anticonvulsants (carbamazepine, phenobarbital, phenytoin, etc.) and antibiotics (rifabutin, rifapentine, etc.)
• Cannot have a history of thrombocytopenia, idiopathic thrombocytopenia purpura (ITP) or have a platelet count of less than 100,000 cells per mm3
• Cannot have any unhealed wounds
• Cannot have any planned surgeries within the next month, including surgical dental procedures
• Cannot have a history of complicated alcohol withdrawal symptoms (including, but not limited to, symptoms such as seizures, hallucinations, and high blood pressure)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Rapamycin (sirolimus) 15mg; Rapamycin (sirolimus) is administered in three 5mg oral capsules. This administration happens once during the first visit.	Drug: Rapamycin; Immunosuppressive drug; Other Names: Sirolimus
PLACEBO_COMPARATOR: Placebo; Placebo is administered in three 5mg oral capsules. This administration happens once during the first visit.	Drug: Placebo; Inert drug; Other Names: Sugar Pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate Safety of a Single 15 mg Dose of Rapamycin (Sirolimus) at First Visit.	Safety will be monitored through adverse events checks by the study physician assistant (PA). The study PA will use the Monitoring of Side-Effects Scale (MOSES) to track if there are any adverse effects. Participants will be recorded as those who report any adverse event vs. no adverse events.	MOSES will be assessed at the first study visit on day 1.
Evaluate Safety of Rapamycin (Sirolimus) at Second Visit.	Safety will be monitored through adverse events checks by the study physician assistant (PA). The study PA will use the Monitoring of Side-Effects Scale (MOSES) to track if there are any adverse effects. Participants will be recorded as those who report any adverse event vs. no adverse events.	MOSES will be assessed at the second study visit, 24 hours after medication administration.
Evaluate Safety of Rapamycin (Sirolimus) at Third (Last) Visit.	Safety will be monitored through adverse events checks by the study physician assistant (PA). The study PA will use the Monitoring of Side-Effects Scale (MOSES) to track if there are any adverse effects. Participants will be recorded as those who report any adverse event vs. no adverse events.	MOSES will be assessed at the third study visit, approximately 10 days after medication administration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drinking Days Between Visit 2 and Visit 3	Participants will be given a timeline to record any drinking that occurs between visits 2 and 3. Time line follow back procedures were used to record daily drinking behavior for all study days; recorded as standard drinks. The total number of days where drinking was recorded is summed for each participants during the study window.	At participant's last study visit, approximately 10-14 days.
Drinks Per Drinking Day Between Visit 2 and Visit 3	Participants will be given a timeline to record any drinking that occurs between visits 2 and 3. Time line follow back procedures were used to record daily drinking behavior for all study days; recorded as standard drinks.	At participant's last study visit, approximately 10 days.
Heavy Drinking Days Between Visit 2 and Visit 3	Participants will be given a timeline to record any drinking that occurs between visits 2 and 3. Time line follow back procedures were used to record daily drinking behavior for all study days; recorded as standard drinks. Heavy drinking days are defined as >=5 drinks per day for Males and >=4 drinks per day for Females.	At participant's last study visit, approximately 10 days.

Collaborators and Investigators

• Sponsor: Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 12, 2018
• Primary Completion (ACTUAL): December 20, 2019
• Study Completion (ACTUAL): January 20, 2020

Study Registration Dates

• First Submitted: November 1, 2018
• First Submitted That Met QC Criteria: November 2, 2018
• First Posted (ACTUAL): November 6, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 27, 2021
• Last Update Submitted That Met QC Criteria: January 7, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: 00073523

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No