Kappa-PET Imaging and Naltrexone in Alcohol Drinking Behaviors

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01625611
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 59
• Location: 1
• Arm: 1
• Duration (Months): 124.9
• Patients Per Site Per Month: 0.5

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
Alcohol Drinking	Drug: Naltrexone	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Kappa-PET Imaging and Naltrexone in Alcohol Drinking Behaviors
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Jun 30, 2021
• Actual Study Completion Date: Jun 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Naltrexone	Drug: Naltrexone; Naltrexone 100 mg titrated over one week; Other Names: Revia

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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

1. 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

• Ages Eligible for Study: 21 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

• Study Protocol and Statistical Analysis Plan - May 6, 2019
• Informed Consent Form: Naltrexone group - Jan 10, 2018
• Informed Consent Form: Healthy control group - Jan 10, 2018

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT01625611
• Other Study ID Numbers: 1011007710; R01AA021818-01A1; U54AA027989
• First Posted: Jun 21, 2012
• Last Update Posted: Aug 10, 2022
• Last Verified: Aug 1, 2022

• Keywords provided by Yale University: Alcohol; Drinking; Drinkers; Alcohol Drinking; Naltrexone; Alcohol Dependence; Alcohol Abuse; Alcohol-Related Disorders; Ethanol; Alcoholism
• Additional relevant MeSH terms: Alcohol Drinking; Drinking Behavior; Naltrexone

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

1. Primary Outcome

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)

2. Primary Outcome

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

3. Secondary Outcome

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
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

[Not Specified]

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.