Alcohol Dependence, Alcohol Use Disorder
Conditions
Brief summary
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.
Interventions
DRUGRapamycin
Immunosuppressive drug
DRUGPlacebo
Inert drug
Sponsors
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate Safety of a Single 15 mg Dose of Rapamycin (Sirolimus) at First Visit. | MOSES will be assessed at the first study visit on day 1. | 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. |
| Evaluate Safety of Rapamycin (Sirolimus) at Second Visit. | MOSES will be assessed at the second study visit, 24 hours after medication administration. | 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. |
| Evaluate Safety of Rapamycin (Sirolimus) at Third (Last) Visit. | MOSES will be assessed at the third study visit, approximately 10 days after medication administration. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Drinking Days Between Visit 2 and Visit 3 | At participant's last study visit, approximately 10-14 days. | 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. |
| Drinks Per Drinking Day Between Visit 2 and Visit 3 | At participant's last study visit, approximately 10 days. | 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 Between Visit 2 and Visit 3 | At participant's last study visit, approximately 10 days. | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rapamycin (Sirolimus) 15mg Rapamycin (sirolimus) is administered in three 5mg oral capsules. This administration happens once during the first visit.
Rapamycin: Immunosuppressive drug | 11 |
| Placebo Placebo is administered in three 5mg oral capsules. This administration happens once during the first visit.
Placebo: Inert drug | 10 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Rapamycin (Sirolimus) 15mg | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 43.1 years STANDARD_DEVIATION 9.9 | 40.6 years STANDARD_DEVIATION 9.2 | 37.8 years STANDARD_DEVIATION 7.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 21 Participants | 10 Participants |
| Region of Enrollment United States | 11 participants | 21 participants | 10 participants |
| Sex: Female, Male Female | 7 Participants | 12 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 9 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 10 |
| other Total, other adverse events | 0 / 11 | 0 / 10 |
| serious Total, serious adverse events | 0 / 11 | 0 / 10 |
Outcome results
Primary
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.
Time frame: MOSES will be assessed at the first study visit on day 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rapamycin (Sirolimus) 15mg | Evaluate Safety of a Single 15 mg Dose of Rapamycin (Sirolimus) at First Visit. | 0 Participants |
| Placebo | Evaluate Safety of a Single 15 mg Dose of Rapamycin (Sirolimus) at First Visit. | 3 Participants |
Primary
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.
Time frame: MOSES will be assessed at the second study visit, 24 hours after medication administration.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rapamycin (Sirolimus) 15mg | Evaluate Safety of Rapamycin (Sirolimus) at Second Visit. | 2 Participants |
| Placebo | Evaluate Safety of Rapamycin (Sirolimus) at Second Visit. | 6 Participants |
Primary
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.
Time frame: MOSES will be assessed at the third study visit, approximately 10 days after medication administration.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rapamycin (Sirolimus) 15mg | Evaluate Safety of Rapamycin (Sirolimus) at Third (Last) Visit. | 3 Participants |
| Placebo | Evaluate Safety of Rapamycin (Sirolimus) at Third (Last) Visit. | 0 Participants |
Secondary
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.
Time frame: At participant's last study visit, approximately 10-14 days.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rapamycin (Sirolimus) 15mg | Drinking Days Between Visit 2 and Visit 3 | 10.5 Days |
| Placebo | Drinking Days Between Visit 2 and Visit 3 | 8 Days |
Secondary
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.
Time frame: At participant's last study visit, approximately 10 days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rapamycin (Sirolimus) 15mg | Drinks Per Drinking Day Between Visit 2 and Visit 3 | 4.8 Standard Drinks/day | Standard Deviation 1.5 |
| Placebo | Drinks Per Drinking Day Between Visit 2 and Visit 3 | 3.2 Standard Drinks/day | Standard Deviation 2.2 |
Secondary
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.
Time frame: At participant's last study visit, approximately 10 days.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rapamycin (Sirolimus) 15mg | Heavy Drinking Days Between Visit 2 and Visit 3 | 5 Days |
| Placebo | Heavy Drinking Days Between Visit 2 and Visit 3 | 2 Days |