Clinical trial NCT02435381: Carisbamate as a Potential Treatment for Alcohol Dependence
Official title: Carisbamate as a Potential Treatment for Alcohol Dependence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Alcohol Dependence
Alcohol Abuse
Substance Abuse
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
First posted: 2015-05-06
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The purpose of this study is to determine the effects of treatment with carisbamate compared to treatment with placebo, on alcohol-induced stimulant and subjective effects in non-treatment seeking alcohol-dependent human volunteers.

Detailed description: This within-subjects placebo-controlled experimental protocol will assess the effects of carisbamate (600mg qd) on the positive subjective effects of alcohol in non-treatment-seeking alcohol-dependent volunteers. Participants will receive study drug (carisbamate or placebo) from days 2- 4. On day 4, study drug will be followed by alcohol (0.8g/kg; 16% by volume) and a placebo beverage (1% by volume as a mask), both separated by 2 hours. Physiologic, subjective effects and BAL will be obtained after the alcohol challenges. Participants will be discharged on day 4 and asked to return a week later to repeat the study under the alternate study drug condition (active carisbamate vs. placebo).

Eligibility criteria: Inclusion Criteria:

1. Be an English-speaking volunteer who is not seeking treatment at the time of the study
2. Be between 18-55 years of age
3. Meet DSM-IV TR criteria for alcohol abuse; participants may or may not meet criteria for nicotine dependence. Nicotine dependence is allowed but not required because most alcohol users smoke cigarettes.
4. Have a self-reported history of using alcohol.
5. Have vital signs as follows: resting pulse must be \< 90 bpm and the blood pressure must be \< 150 mmHg systolic and \< 90 mmHg diastolic.
6. Have hematology and chemistry laboratory tests that are within normal (+/- 10%) limits with the following exceptions:

   * liver function tests (total bilirubin, ALT, AST, and alkaline phosphatase) \< 3 x the upper limit of normal, and b) kidney function tests (creatinine and BUN) within normal limits
7. Have a baseline EKG that demonstrates clinically normal sinus rhythm, clinically normal conduction, and no clinically significant arrhythmias
8. Have a medical history and brief physical examination demonstrating no clinically significant contraindications for study participation, in the judgment of the admitting physician and the principal investigator.

Exclusion Criteria:

1. Meet DSM IV TR criteria for dependence on drugs other than alcohol or nicotine.
2. Have any history or evidence suggestive of seizure disorder or brain injury
3. Have any previous medically adverse reaction to alcohol, including loss of consciousness, chest pain, or epileptic seizure
4. Have neurological or psychiatric disorders, such as:

   * psychosis, bipolar illness or major depression as assessed by SCID
   * organic brain disease or dementia assessed by clinical interview
   * history of any psychiatric disorder which would require ongoing treatment or which would make study compliance difficult
   * history of suicide attempts within the past year and/or current suicidal ideation/plan
5. Have evidence of clinically significant heart disease or hypertension, as determined by the PI
6. Have evidence of untreated or unstable medical illness including: neuroendocrine, autoimmune, renal, hepatic, or active infectious disease
7. Have symptomatic HIV or are taking antiretroviral medication
8. Be pregnant or nursing. Other females must either be unable to conceive (i.e., surgically sterilized, sterile, or post-menopausal) or be using a reliable form of contraception (e.g., abstinence, birth control pills, intrauterine device, condoms, or spermicide). All females must provide negative pregnancy urine tests before study entry, upon hospital admission, and at the end of study participation
9. Have any other illness, condition, or use of psychotropic medications, which in the opinion of the PI and/or the admitting physician would preclude safe and/or successful completion of the study.
10. Currently seeking help for alcohol dependence.
11. Subjects with or prone to clinically significant alcohol withdrawal.
12. More than thirty days of abstinence from alcohol in the ninety days prior to enrollment.
13. A history of major alcohol-related medical complications requiring hospitalization (i.e. pancreatitis).
14. Contraindication(s) to take the study medication such as renal or hepatic impairment, nephrolithiasis, congenital metabolic disorders or history of seizures. Moderate-to-severe renal impairment defined as creatinine clearance less than 30 mL/min.
15. Use of inhibitors/substrates for renal cationic transporters, or medications contraindicated with ethanol.
16. A history of violence or aggression, assessed as part of the clinical interview at screening visit.

Primary outcomes:
measure: Mean Biphasic Alcohol Effects Scale (BAES) Scores
timeFrame: 15, 30 and 60 minutes after consumption of placebo (1% alcohol by volume) and alcohol (0.8g/kg; 16% by volume) beverages, stimulant ratings
measure: Mean Alcohol Urge Questionnaire (AUQ) Scores
timeFrame: 15, 30 and 60 minutes after consumption of placebo (1% alcohol by volume) and alcohol (0.8g/kg; 16% by volume) beverages.
measure: Mean Positive and Negative Affect Schedule (PANAS) Scores
timeFrame: 15, 30 and 60 minutes after consumption of placebo (1% alcohol by volume) and alcohol (0.8g/kg; 16% by volume) beverages.
measure: MEAN DRUG EFFECTS QUESTIONNAIRE (DEQ) SCORES
timeFrame: 15, 30 and 60 minutes after consumption of placebo (1% alcohol by volume) and alcohol (0.8g/kg; 16% by volume) beverages.
Secondary outcomes:
measure: Physiologic Effects of Carisbamate: Mean Systolic and Diastolic Blood Pressure
timeFrame: 15, 30 and 60 minutes after alcohol (0.8 mg/kg;16% by volume) consumption
measure: Physiologic Effects of Carisbamate: Mean Heart Rate
timeFrame: 15, 30 and 60 minutes after alcohol (0.8 mg/kg;16% by volume) consumption
Other outcomes:
Locations:
city: Houston
country: United States
facility: Michael E. DeBakey VA Medical Center
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Thomas F Newton, M.D
role: PRINCIPAL_INVESTIGATOR
References: