Alcoholism
Conditions
Brief summary
This is a study involving treatment for alcohol dependence among males of European or Asian decent. The ultimate aim of this line of investigation is to further establish a genetic link between alcohol dependence and treatment by defining an endophenotype associated with treatment response. The study consists of two inpatient alcohol challenge sessions with treatment using random assignment to either naltrexone or placebo.
Detailed description
Despite the well-established efficacy of naltrexone, there are significant variations in individual responses to naltrexone. A critical question remains: under what circumstances and for which patients will naltrexone be most beneficial? Recent work at our center provides evidence that the mu-opioid receptor (OPRM1) gene polymorphism A118G (Asn40Asp) imparts a significant change in treatment response. We have shown that patients with Asn40 variant (absence of heavy drinking -73.9% v/s 49% response). To further consolidate our knowledge, we wish to test the relationship between A118G polymorphism and the subjective/objective measures to alcohol among alcoholics treated with naltrexone. This work is focused on subjects of European or Asian decent as the A118G polymorphism occurs in less than 1% of those of African decent. Up to 40 subjects will be recruited. The subjects were admitted to the UPenn Translational Research Center and receive two alcohol challenge sessions after pretreatment with naltrexone or placebo.
Interventions
DRUGPlacebo Oral Tablet
Placebo pill
DRUGNaltrexone
50 mg of naltrexone prior to challenge session
Sponsors
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Groups 1 and 3 get placebo in session 1 and placebo in session 2, Groups 2 and 4 get placebo in session 1 and naltrexone in session 2
Eligibility
Sex/Gender
MALE
Age
21 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
1. Males 21 years of age or older of European or Asian decent. 2. Has a current DSM IV diagnosis of alcohol dependence as determined by the Structural Clinical Interview for DSM IV (SCID-IV Mini). 3. Drank an average of 21 drinks/week in the 60 days prior to treatment and had at least 2 occasions of heavy drinking (5 or more drinks on a given day for men), as measured by the Timeline Followback (TLFB). 4. Has adequate vision, hearing, and ability to communicate to allow study participation. 5. Successfully completes detoxification as manifested by at least 48 consecutive hours of no self-reported alcohol use immediately prior to admission to the inpatient unit. 6. Has signed a witnessed informed consent 7. Scores below an 8 on the Clinical Inventory of Withdrawal for Alcohol (CIWA) prior to starting naltrexone/placebo; and 8) Can speak, print, and understand English.
Exclusion criteria
1. Meets DSM-IV criteria for dependence on any substance other than alcohol or nicotine in the last 6 months. 2. Tests positive on the urine drug screen for opioids, cocaine, or amphetamine at the screening visit (only 1 repeat test permitted). 3. Meets current or lifetime DSM-IV criteria for bipolar affective disorder, schizophrenia, or any psychotic disorder 4. The presence of unstable or serious medical illness, including history of stroke, seizure disorder, severe liver disease (AST or ALT \> 5x normal at the time of randomization), or unstable cardiac disease 5. Has taken any psychotropic medications (including disulfiram) regularly within the last seven days prior to randomization (14 days for fluoxetine) or needs immediate treatment with a psychotropic medication (with the exception of detoxification medications or benadryl used sparingly for sleep) 6. Over age 64 and has evidence of severe cognitive impairment as evidenced by a Mini-mental status exam (MMSE) score \<24 7. Has suicidal or homicidal ideation necessitating inpatient hospitalization 8. Has been abstinent more than 14 days prior to Phase 1 9. Is of African Descent 10. Meets current DSM-IV criteria for for major depression (non-substance induced), PTSD, or panic disorder. 11. Has significant hematological, pulmonary, endocrine, cardiovascular, renal, or gastrointestinal disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biphasic Alcohol Effects Scale:Total Mood | during 2nd alcohol challenge session | Change from baseline to peak cortisol response, during the 2nd alcohol challenge session, subjective response as measured by Biphasic Alcohol Effects Scale: Total Mood. Biphasic Alcohol Effects Scale: Total Mood: minimum = 0, maximum = 106, higher scores indicate better outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adrenocorticotropic Hormone (ACTH) Levels | during 2nd alcohol challenge session | Change from baseline to peak cortisol response during the 2nd alcohol challenge session, objective response as measured by Adrenocorticotropic hormone (ACTH). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1: Asn40 Placebo Placebo Asn40: Placebo, Placebo
Each alcohol challenge session preceded by pretreatment with placebo
Placebo: placebo pills
alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice | 6 |
| Group 2: Asn40 Placebo Naltrexone Asn40: Placebo, Naltrexone
The first alcohol challenge session preceded by pretreatment with placebo. The second challegne alcohol session preceded by pretreatment with naltrexone 50 mg as a single dose.
Placebo: placebo pills
naltrexone: 50 mg of naltrexone prior to challenge session
alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice | 8 |
| Group 3: Asp40 Placebo Placebo Asp40: Placebo, Placebo
Each alcohol challenge session preceded by pretreatment with placebo
Placebo: placebo pills
alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice | 4 |
| Group 4: Asp40 Placebo Naltrexone Asp40: Placebo, Naltrexone
The first alcohol challenge session preceded by pretreatment with placebo. The second alcohol challenge session preceded by pretreatment with naltrexone 50 mg as a single dose.
Placebo: placebo pills
naltrexone: 50 mg of naltrexone prior to challenge session
alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice | 6 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| First Alcohol Challenge | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Second Alcohol Challenge | Lost to Follow-up | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Group 2: Asn40 Placebo Naltrexone | Group 3: Asp40 Placebo Placebo | Group 1: Asn40 Placebo Placebo | Group 4: Asp40 Placebo Naltrexone | Total |
|---|---|---|---|---|---|
| Age, Customized <21 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Between 21 and 65 years | 8 Participants | 4 Participants | 6 Participants | 6 Participants | 24 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 4 Participants | 6 Participants | 6 Participants | 24 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 4 Participants | 6 Participants | 6 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 8 | 0 / 4 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 0 / 8 | 0 / 4 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 8 | 0 / 4 | 0 / 6 |
Outcome results
Primary
Biphasic Alcohol Effects Scale:Total Mood
Change from baseline to peak cortisol response, during the 2nd alcohol challenge session, subjective response as measured by Biphasic Alcohol Effects Scale: Total Mood. Biphasic Alcohol Effects Scale: Total Mood: minimum = 0, maximum = 106, higher scores indicate better outcomes.
Time frame: during 2nd alcohol challenge session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Asn40 Placebo Placebo | Biphasic Alcohol Effects Scale:Total Mood | 6.94 units on a scale | Standard Deviation 9.53 |
| Group 2: Asn40 Placebo Naltrexone | Biphasic Alcohol Effects Scale:Total Mood | 3.57 units on a scale | Standard Deviation 18.46 |
| Group 3: Asp40 Placebo Placebo | Biphasic Alcohol Effects Scale:Total Mood | 6.50 units on a scale | Standard Deviation 4.04 |
| Group 4: Asp40 Placebo Naltrexone | Biphasic Alcohol Effects Scale:Total Mood | 3.20 units on a scale | Standard Deviation 8.11 |
Secondary
Adrenocorticotropic Hormone (ACTH) Levels
Change from baseline to peak cortisol response during the 2nd alcohol challenge session, objective response as measured by Adrenocorticotropic hormone (ACTH).
Time frame: during 2nd alcohol challenge session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Asn40 Placebo Placebo | Adrenocorticotropic Hormone (ACTH) Levels | -7.83 pg/ml | Standard Deviation 14.34 |
| Group 2: Asn40 Placebo Naltrexone | Adrenocorticotropic Hormone (ACTH) Levels | 3.86 pg/ml | Standard Deviation 7.47 |
| Group 3: Asp40 Placebo Placebo | Adrenocorticotropic Hormone (ACTH) Levels | 5.25 pg/ml | Standard Deviation 8.42 |
| Group 4: Asp40 Placebo Naltrexone | Adrenocorticotropic Hormone (ACTH) Levels | -3.20 pg/ml | Standard Deviation 14.1 |