Trial Outcomes & Findings for Citalopram Effects on Craving and Dopamine Receptor Availability in Alcoholics (NCT NCT01657760)
NCT ID: NCT01657760
Last Updated: 2019-07-23
Results Overview
To assess whether craving for alcohol in alcohol dependence is affected by iv citalopram, compared to placebo. Cue-induced craving for alcohol was assessed using the Alcohol Urge Questionnaire, composed of 8 questions with responses on a 0 (none) to 7 (severe or highest level) which when scored provide an estimate of the level of craving for alcohol for the participant. A maximum score is thus 56, indicating the highest level of craving for alcohol, whereas the minimum score of 0 indicates no appreciable craving for alcohol.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
31 participants
Primary outcome timeframe
5 minutes after 1 hour of infusion intervention
Results posted on
2019-07-23
Participant Flow
Alcohol-dependent (AD) and healthy control (HC) participants were screened via the SCID-IV, excluding any participants with any Axis I psychiatric diagnosis within the last 6 months (aside from and alcohol dependence in the AD group). Fourteen potential AD and seventeen potential HC participants were enrolled and screened.
Enrolled participants who did not start study procedures either decided not to participate or failed screening.
Participant milestones
| Measure |
Alcohol Dependent Citalopram First Placebo Second
DSM-IV alcohol dependent participants.
Qualifying participants were invited back for three subsequent visits: a structural MRI scan, and two study medication/\[18F\]-fallypride PET scanning days (citalopram 40 mg iv, or saline placebo, double-blinded, administered in counter-balancing order) more than 1 week apart. All completing participants had breathalyzer-confirmed exhaled alcohol concentration of 0, and low alcohol withdrawal scores (confirming no intoxication and minimal alcohol withdrawal symptoms) on all study visits (see below). On study medication/PET scanning days, the following procedures were completed in order: 1. Breathalyzer, withdrawal, and psychiatric symptomatology screening; 2. Intravenous citalopram (or saline placebo) infusion (1 h). 3. Cue-induced craving assessment (\~20 minutes). 4. \[18F\]-fallypride PET scanning (\~3 h).
|
Alcohol Dependent Placebo First Citalopram Second
DSM-IV alcohol dependent participants.
Qualifying participants were invited back for three subsequent visits: a structural MRI scan, and two study medication/\[18F\]-fallypride PET scanning days (citalopram 40 mg iv, or saline placebo, double-blinded, administered in counter-balancing order) more than 1 week apart. All completing participants had breathalyzer-confirmed exhaled alcohol concentration of 0, and low alcohol withdrawal scores (confirming no intoxication and minimal alcohol withdrawal symptoms) on all study visits (see below). On study medication/PET scanning days, the following procedures were completed in order: 1. Breathalyzer, withdrawal, and psychiatric symptomatology screening; 2. Intravenous citalopram (or saline placebo) infusion (1 h). 3. Cue-induced craving assessment (\~20 minutes). 4. \[18F\]-fallypride PET scanning (\~3 h).
|
Healthy Control Citalopram First Placebo Second
participants with no Axis I mental illness or substance use disorder.
Same procedures as AD group
|
Healthy Control Placebo First Citalopram Second
participants with no Axis I mental illness or substance use disorder.
Same procedures as AD group
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
5
|
7
|
7
|
7
|
|
Overall Study
COMPLETED
|
4
|
6
|
6
|
4
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
1
|
3
|
Reasons for withdrawal
| Measure |
Alcohol Dependent Citalopram First Placebo Second
DSM-IV alcohol dependent participants.
Qualifying participants were invited back for three subsequent visits: a structural MRI scan, and two study medication/\[18F\]-fallypride PET scanning days (citalopram 40 mg iv, or saline placebo, double-blinded, administered in counter-balancing order) more than 1 week apart. All completing participants had breathalyzer-confirmed exhaled alcohol concentration of 0, and low alcohol withdrawal scores (confirming no intoxication and minimal alcohol withdrawal symptoms) on all study visits (see below). On study medication/PET scanning days, the following procedures were completed in order: 1. Breathalyzer, withdrawal, and psychiatric symptomatology screening; 2. Intravenous citalopram (or saline placebo) infusion (1 h). 3. Cue-induced craving assessment (\~20 minutes). 4. \[18F\]-fallypride PET scanning (\~3 h).
|
Alcohol Dependent Placebo First Citalopram Second
DSM-IV alcohol dependent participants.
Qualifying participants were invited back for three subsequent visits: a structural MRI scan, and two study medication/\[18F\]-fallypride PET scanning days (citalopram 40 mg iv, or saline placebo, double-blinded, administered in counter-balancing order) more than 1 week apart. All completing participants had breathalyzer-confirmed exhaled alcohol concentration of 0, and low alcohol withdrawal scores (confirming no intoxication and minimal alcohol withdrawal symptoms) on all study visits (see below). On study medication/PET scanning days, the following procedures were completed in order: 1. Breathalyzer, withdrawal, and psychiatric symptomatology screening; 2. Intravenous citalopram (or saline placebo) infusion (1 h). 3. Cue-induced craving assessment (\~20 minutes). 4. \[18F\]-fallypride PET scanning (\~3 h).
|
Healthy Control Citalopram First Placebo Second
participants with no Axis I mental illness or substance use disorder.
Same procedures as AD group
|
Healthy Control Placebo First Citalopram Second
participants with no Axis I mental illness or substance use disorder.
Same procedures as AD group
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
|
Overall Study
Physician Decision
|
1
|
1
|
1
|
2
|
Baseline Characteristics
31 subjects enrolled, only 20 completed the study
Baseline characteristics by cohort
| Measure |
Alcohol Dependent
n=10 Participants
DSM-IV alcohol dependent
|
Healthy Control
n=10 Participants
participants with no Axis I illness or substance use disorder
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38 years
STANDARD_DEVIATION 7.6 • n=99 Participants
|
41 years
STANDARD_DEVIATION 7.9 • n=107 Participants
|
39.5 years
STANDARD_DEVIATION 7.8 • n=206 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants • 31 subjects enrolled, only 20 completed the study
|
5 Participants
n=107 Participants • 31 subjects enrolled, only 20 completed the study
|
7 Participants
n=206 Participants • 31 subjects enrolled, only 20 completed the study
|
|
Sex: Female, Male
Male
|
8 Participants
n=99 Participants • 31 subjects enrolled, only 20 completed the study
|
5 Participants
n=107 Participants • 31 subjects enrolled, only 20 completed the study
|
13 Participants
n=206 Participants • 31 subjects enrolled, only 20 completed the study
|
|
Race/Ethnicity, Customized
Race · White
|
5 Participants
n=99 Participants • 31 enrolled, 20 completed the study
|
4 Participants
n=107 Participants • 31 enrolled, 20 completed the study
|
9 Participants
n=206 Participants • 31 enrolled, 20 completed the study
|
|
Race/Ethnicity, Customized
Race · African American
|
4 Participants
n=99 Participants • 31 enrolled, 20 completed the study
|
5 Participants
n=107 Participants • 31 enrolled, 20 completed the study
|
9 Participants
n=206 Participants • 31 enrolled, 20 completed the study
|
|
Race/Ethnicity, Customized
Race · Asian
|
1 Participants
n=99 Participants • 31 enrolled, 20 completed the study
|
1 Participants
n=107 Participants • 31 enrolled, 20 completed the study
|
2 Participants
n=206 Participants • 31 enrolled, 20 completed the study
|
|
Region of Enrollment
United States
|
10 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 5 minutes after 1 hour of infusion interventionPopulation: All participants completed both arms
To assess whether craving for alcohol in alcohol dependence is affected by iv citalopram, compared to placebo. Cue-induced craving for alcohol was assessed using the Alcohol Urge Questionnaire, composed of 8 questions with responses on a 0 (none) to 7 (severe or highest level) which when scored provide an estimate of the level of craving for alcohol for the participant. A maximum score is thus 56, indicating the highest level of craving for alcohol, whereas the minimum score of 0 indicates no appreciable craving for alcohol.
Outcome measures
| Measure |
Alcohol Dependent Citalopram Infusion
n=10 Participants
40 mg citalopram in 250 ml saline infused over 1 hour, in a double-blind, crossover study, with infusion days at least 2 weeks apart.
citalopram: citalopram, 40 mg IV, vs. saline control, each to be administered in a double-blinded, within-subjects design.
|
Alcohol Dependent Placebo
n=10 Participants
Intravenous saline control, in a double-blind, crossover study, with infusion days at least 2 weeks apart.
citalopram: citalopram, 40 mg IV, vs. saline control, each to be administered in a double-blinded, within-subjects design.
|
Healthy Control Citalopram Infusion
n=10 Participants
40 mg citalopram in 250 ml saline infused over 1 hour, in a double-blind, crossover study, with infusion days at least 2 weeks apart.
citalopram: citalopram, 40 mg IV, vs. saline control, each to be administered in a double-blinded, within-subjects design.
|
Healthy Control Placebo Infusion
n=10 Participants
Intravenous saline control, in a double-blind, crossover study, with infusion days at least 2 weeks apart.
citalopram: citalopram, 40 mg IV, vs. saline control, each to be administered in a double-blinded, within-subjects design.
|
|---|---|---|---|---|
|
Craving for Alcohol in Alcohol Dependence With Citalopram Compared to Placebo
|
21 score on a scale
Standard Deviation 14.6
|
30.4 score on a scale
Standard Deviation 17.9
|
10.8 score on a scale
Standard Deviation 4.5
|
10.6 score on a scale
Standard Deviation 3.7
|
SECONDARY outcome
Timeframe: 2-3 hours after 1 hour citalopram or placebo infusionrelative binding potential of dopamine D2/3 receptor specific tracer compared to cerebellum, where there is known to be almost no dopamine receptors.
Outcome measures
| Measure |
Alcohol Dependent Citalopram Infusion
n=10 Participants
40 mg citalopram in 250 ml saline infused over 1 hour, in a double-blind, crossover study, with infusion days at least 2 weeks apart.
citalopram: citalopram, 40 mg IV, vs. saline control, each to be administered in a double-blinded, within-subjects design.
|
Alcohol Dependent Placebo
n=10 Participants
Intravenous saline control, in a double-blind, crossover study, with infusion days at least 2 weeks apart.
citalopram: citalopram, 40 mg IV, vs. saline control, each to be administered in a double-blinded, within-subjects design.
|
Healthy Control Citalopram Infusion
n=10 Participants
40 mg citalopram in 250 ml saline infused over 1 hour, in a double-blind, crossover study, with infusion days at least 2 weeks apart.
citalopram: citalopram, 40 mg IV, vs. saline control, each to be administered in a double-blinded, within-subjects design.
|
Healthy Control Placebo Infusion
n=10 Participants
Intravenous saline control, in a double-blind, crossover study, with infusion days at least 2 weeks apart.
citalopram: citalopram, 40 mg IV, vs. saline control, each to be administered in a double-blinded, within-subjects design.
|
|---|---|---|---|---|
|
Striatal Dopamine Receptor Availability in Alcohol Dependence With Citalopram, Compared to Placebo
|
22.4 striatal binding potential ratio
Standard Deviation 4.0
|
25.7 striatal binding potential ratio
Standard Deviation 5.1
|
22.5 striatal binding potential ratio
Standard Deviation 3.8
|
21.3 striatal binding potential ratio
Standard Deviation 4.7
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Citalopram Infusion
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=20 participants at risk
Intravenous saline control, in a double-blind, crossover study, with infusion days at least 2 weeks apart.
citalopram: citalopram, 40 mg IV, vs. saline control, each to be administered in a double-blinded, within-subjects design.
|
Citalopram Infusion
n=20 participants at risk
40 mg citalopram in 250 ml saline infused over 1 hour, in a double-blind, crossover study, with infusion days at least 2 weeks apart.
citalopram: citalopram, 40 mg IV, vs. saline control, each to be administered in a double-blinded, within-subjects design.
|
|---|---|---|
|
Gastrointestinal disorders
nausea
|
5.0%
1/20 • Number of events 1 • two weeks of study procedures per participant
Adverse events were collected on all study days, both upon initial participant contact, during the study procedures, and upon completing each day's study procedures.
|
40.0%
8/20 • Number of events 8 • two weeks of study procedures per participant
Adverse events were collected on all study days, both upon initial participant contact, during the study procedures, and upon completing each day's study procedures.
|
|
Nervous system disorders
anxiety
|
5.0%
1/20 • Number of events 1 • two weeks of study procedures per participant
Adverse events were collected on all study days, both upon initial participant contact, during the study procedures, and upon completing each day's study procedures.
|
0.00%
0/20 • two weeks of study procedures per participant
Adverse events were collected on all study days, both upon initial participant contact, during the study procedures, and upon completing each day's study procedures.
|
|
Nervous system disorders
dizziness
|
10.0%
2/20 • Number of events 2 • two weeks of study procedures per participant
Adverse events were collected on all study days, both upon initial participant contact, during the study procedures, and upon completing each day's study procedures.
|
25.0%
5/20 • Number of events 5 • two weeks of study procedures per participant
Adverse events were collected on all study days, both upon initial participant contact, during the study procedures, and upon completing each day's study procedures.
|
|
Gastrointestinal disorders
dyspepsia
|
5.0%
1/20 • Number of events 1 • two weeks of study procedures per participant
Adverse events were collected on all study days, both upon initial participant contact, during the study procedures, and upon completing each day's study procedures.
|
0.00%
0/20 • two weeks of study procedures per participant
Adverse events were collected on all study days, both upon initial participant contact, during the study procedures, and upon completing each day's study procedures.
|
|
Nervous system disorders
fatigue
|
10.0%
2/20 • Number of events 2 • two weeks of study procedures per participant
Adverse events were collected on all study days, both upon initial participant contact, during the study procedures, and upon completing each day's study procedures.
|
35.0%
7/20 • Number of events 7 • two weeks of study procedures per participant
Adverse events were collected on all study days, both upon initial participant contact, during the study procedures, and upon completing each day's study procedures.
|
|
Musculoskeletal and connective tissue disorders
muscle tension
|
10.0%
2/20 • Number of events 2 • two weeks of study procedures per participant
Adverse events were collected on all study days, both upon initial participant contact, during the study procedures, and upon completing each day's study procedures.
|
10.0%
2/20 • Number of events 2 • two weeks of study procedures per participant
Adverse events were collected on all study days, both upon initial participant contact, during the study procedures, and upon completing each day's study procedures.
|
|
Nervous system disorders
insomnia
|
0.00%
0/20 • two weeks of study procedures per participant
Adverse events were collected on all study days, both upon initial participant contact, during the study procedures, and upon completing each day's study procedures.
|
5.0%
1/20 • Number of events 1 • two weeks of study procedures per participant
Adverse events were collected on all study days, both upon initial participant contact, during the study procedures, and upon completing each day's study procedures.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place