Altering Memories That Increase Risk of Relapse in Alcohol Use Disorders

Study Overview
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Brief Summary
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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.

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

Conditions
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Alcohol Use Disorder, Alcohol Dependence

Intervention / Treatment
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* Drug: Rapamycin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rapamycin (sirolimus) 15mg<br>Rapamycin (sirolimus) is administered in three 5mg oral capsules. This administration happens once during the first visit. | Drug: Rapamycin<br>* Immunosuppressive drug<br>* Other names: Sirolimus;|
| Placebo Comparator: Placebo<br>Placebo is administered in three 5mg oral capsules. This administration happens once during the first visit. | Drug: Placebo<br>* Inert drug<br>* Other names: Sugar Pill;|

What is the study measuring?
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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. |