Kappa-PET Imaging and Naltrexone in Alcohol Drinking Behaviors
Study Details
Study Description
Brief Summary
The primary purpose of the study is to increase our knowledge of receptor function in the brains of people who are heavy drinkers and taking naltrexone (NTX), a medication that has been approved for the treatment of alcohol dependence. Receptors are special molecules in the brain to which other molecules (neurotransmitters) attach during the normal every-day workings of the brain. Drugs can bind to those receptor molecules as well. Recent evidence suggests that kappa opioid receptors (KOR's) may play an important role in alcohol drinking behavior. This study will try to determine if naltrexone's ability to attach to these receptors is related to its effectiveness. We will use PET (positron emission tomography) for this study. PET is a type of imaging device found in nuclear medicine. It is used for tracking the presence of injected radioactive materials in the body.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Naltrexone
|
Drug: Naltrexone
Naltrexone 100 mg titrated over one week
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Occupancy of KOR by NTX and Drinking [6-8 days after treatment with naltrexone]
To determine the degree to which occupancy of KORs by a 100 mg/day dose of NTX mediates (influences the strength of) responsivity to NTX treatment in all heavy drinkers.
- Relationship Between NTX Responsivity and Occupancy of KOR [6-8 days after treatment with naltrexone]
To determine whether the relationship between NTX responsivity and occupancy of KOR is different in family history positive vs. family history negative heavy drinkers. Evaluations were done with a logistic regression which included years of drinking (a covariate), family history status, and occupancy of KOR. The logistic model calculated a probability of response, defined as a 50% or greater reduction in drinking after naltrexone, for every participant. Reported outcome is the area under the ROC produced by the model. The closer the value is to 100 percent probability, the better the model is at correctly classifying the observations.
Secondary Outcome Measures
- Baseline KOR Differences [at baseline prior to treatment with naltrexone]
To determine if baseline levels of KOR differ between family history positive (FHP) and family history negative (FHN) heavy drinkers and to determine if baseline KOR level is related to either baseline drinking or responsivity to NTX.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Ages 21-50
-
Able to read English at 6th grade level or higher and to complete study evaluations
-
Regular alcohol drinker
Exclusion Criteria:
-
Individuals who are seeking alcohol treatment
-
Medical conditions that would contraindicate the use of study medication
-
Regular use of other substances
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Sac, Cmhc | New Haven | Connecticut | United States | 06519 |
Sponsors and Collaborators
- Yale University
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators
- Principal Investigator: Suchitra Krishnan-Sarin, Ph.D., Yale University
Study Documents (Full-Text)
More Information
Publications
None provided.- 1011007710
- R01AA021818-01A1
- U54AA027989
Study Results
Participant Flow
Recruitment Details | Participants were recruited from the community through various methods such as flyers and online. |
---|---|
Pre-assignment Detail | All enrolled participants were assigned to a study arm. |
Arm/Group Title | Naltrexone | Healthy Controls |
---|---|---|
Arm/Group Description | Naltrexone: Naltrexone 100 mg titrated over one week | No treatment, baseline measurements only. |
Period Title: Overall Study | ||
STARTED | 55 | 4 |
PET Scan 1 | 49 | 4 |
Lab 2 | 48 | 0 |
PET Scan 2 | 47 | 0 |
COMPLETED | 47 | 4 |
NOT COMPLETED | 8 | 0 |
Baseline Characteristics
Arm/Group Title | Naltrexone | Healthy Controls | Total |
---|---|---|---|
Arm/Group Description | Naltrexone: Naltrexone 100 mg titrated over one week | No treatment, baseline measurements only. | Total of all reporting groups |
Overall Participants | 47 | 4 | 51 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
32
(3.9)
|
35.6
(11.4)
|
33.8
(7.7)
|
Sex: Female, Male (Count of Participants) | |||
Female |
16
34%
|
3
75%
|
19
37.3%
|
Male |
31
66%
|
1
25%
|
32
62.7%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
8
17%
|
0
0%
|
8
15.7%
|
Not Hispanic or Latino |
39
83%
|
4
100%
|
43
84.3%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
0
0%
|
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
Black or African American |
22
46.8%
|
0
0%
|
22
43.1%
|
White |
24
51.1%
|
4
100%
|
28
54.9%
|
More than one race |
1
2.1%
|
0
0%
|
1
2%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Region of Enrollment (participants) [Number] | |||
United States |
47
100%
|
4
100%
|
51
100%
|
Outcome Measures
Title | Occupancy of KOR by NTX and Drinking |
---|---|
Description | To determine the degree to which occupancy of KORs by a 100 mg/day dose of NTX mediates (influences the strength of) responsivity to NTX treatment in all heavy drinkers. |
Time Frame | 6-8 days after treatment with naltrexone |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Naltrexone |
---|---|
Arm/Group Description | Naltrexone: Naltrexone 100 mg titrated over one week |
Measure Participants | 44 |
Mean (Standard Error) [% Occupancy] |
92
(1)
|
Title | Relationship Between NTX Responsivity and Occupancy of KOR |
---|---|
Description | To determine whether the relationship between NTX responsivity and occupancy of KOR is different in family history positive vs. family history negative heavy drinkers. Evaluations were done with a logistic regression which included years of drinking (a covariate), family history status, and occupancy of KOR. The logistic model calculated a probability of response, defined as a 50% or greater reduction in drinking after naltrexone, for every participant. Reported outcome is the area under the ROC produced by the model. The closer the value is to 100 percent probability, the better the model is at correctly classifying the observations. |
Time Frame | 6-8 days after treatment with naltrexone |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Naltrexone |
---|---|
Arm/Group Description | Naltrexone: Naltrexone 100 mg titrated over one week |
Measure Participants | 44 |
Number [percent probability] |
84
|
Title | Baseline KOR Differences |
---|---|
Description | To determine if baseline levels of KOR differ between family history positive (FHP) and family history negative (FHN) heavy drinkers and to determine if baseline KOR level is related to either baseline drinking or responsivity to NTX. |
Time Frame | at baseline prior to treatment with naltrexone |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Naltrexone - FH Positive | Naltrexone - FH Negative |
---|---|---|
Arm/Group Description | Naltrexone: Naltrexone 100 mg titrated over one week | Naltrexone: Naltrexone 100 mg titrated over one week |
Measure Participants | 29 | 18 |
Mean (Standard Error) [% Occupancy] |
91.2
(1.7)
|
94.2
(1.9)
|
Adverse Events
Time Frame | Approximately 3 weeks | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | Naltrexone | Healthy Controls | ||
Arm/Group Description | Naltrexone: Naltrexone 100 mg titrated over one week | No treatment, baseline measurements only. | ||
All Cause Mortality |
||||
Naltrexone | Healthy Controls | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/55 (0%) | 0/4 (0%) | ||
Serious Adverse Events |
||||
Naltrexone | Healthy Controls | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/55 (0%) | 0/4 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Naltrexone | Healthy Controls | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 37/55 (67.3%) | 0/4 (0%) | ||
Gastrointestinal disorders | ||||
Nausea | 19/55 (34.5%) | 22 | 0/4 (0%) | 0 |
Vomiting | 6/55 (10.9%) | 7 | 0/4 (0%) | 0 |
Diarrhea | 6/55 (10.9%) | 7 | 0/4 (0%) | 0 |
Abdominal discomfort | 3/55 (5.5%) | 3 | 0/4 (0%) | 0 |
Constipation | 2/55 (3.6%) | 2 | 0/4 (0%) | 0 |
Dry mouth | 1/55 (1.8%) | 1 | 0/4 (0%) | 0 |
Stomach ache | 1/55 (1.8%) | 1 | 0/4 (0%) | 0 |
Upset stomach | 1/55 (1.8%) | 2 | 0/4 (0%) | 0 |
Apetite change | 5/55 (9.1%) | 5 | 0/4 (0%) | 0 |
General disorders | ||||
Fatigue | 4/55 (7.3%) | 4 | 0/4 (0%) | 0 |
Insomnia | 1/55 (1.8%) | 1 | 0/4 (0%) | 0 |
Drowsiness | 2/55 (3.6%) | 3 | 0/4 (0%) | 0 |
Cloudy | 1/55 (1.8%) | 1 | 0/4 (0%) | 0 |
Cold sweat | 1/55 (1.8%) | 1 | 0/4 (0%) | 0 |
Hypothermia | 1/55 (1.8%) | 1 | 0/4 (0%) | 0 |
Decreased desired to drink | 1/55 (1.8%) | 1 | 0/4 (0%) | 0 |
Feeling high | 3/55 (5.5%) | 3 | 0/4 (0%) | 0 |
Feeling good | 1/55 (1.8%) | 2 | 0/4 (0%) | 0 |
Tightness in chest | 1/55 (1.8%) | 1 | 0/4 (0%) | 0 |
Tired | 3/55 (5.5%) | 3 | 0/4 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||
Muscle tightness | 1/55 (1.8%) | 1 | 0/4 (0%) | 0 |
Nervous system disorders | ||||
Headache | 9/55 (16.4%) | 10 | 0/4 (0%) | 0 |
Tremor | 2/55 (3.6%) | 2 | 0/4 (0%) | 0 |
Psychiatric disorders | ||||
Anxiety | 3/55 (5.5%) | 3 | 0/4 (0%) | 0 |
Depression | 1/55 (1.8%) | 1 | 0/4 (0%) | 0 |
Irritability | 1/55 (1.8%) | 2 | 0/4 (0%) | 0 |
Renal and urinary disorders | ||||
Frequent urination | 3/55 (5.5%) | 3 | 0/4 (0%) | 0 |
Reproductive system and breast disorders | ||||
Decreased sex drive | 3/55 (5.5%) | 3 | 0/4 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||
Congestion | 1/55 (1.8%) | 1 | 0/4 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||
Peeling hands | 1/55 (1.8%) | 1 | 0/4 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Dr. Krishnan-Sarin |
---|---|
Organization | Yale University |
Phone | 203.974.7595 |
nicholas.franco@yale.edu |
- 1011007710
- R01AA021818-01A1
- U54AA027989