Citalopram Effects on Craving and Dopamine Receptor Availability in Alcoholics (CECDRAAD)

• ClinicalTrials.gov Identifier: NCT01657760
• Recruitment Status: Completed
• First Posted: August 6, 2012
• Results First Posted: July 23, 2019
• Last Update Posted: July 23, 2019
• Sponsor: VA Office of Research and Development
• Information provided by (Responsible Party): VA Office of Research and Development

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Basic Science
• Condition: Alcohol Dependence
• Intervention: Drug: citalopram
• Enrollment: 31

Participant Flow

Recruitment Details	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.
Pre-assignment Details	Enrolled participants who did not start study procedures either decided not to participate or failed screening.

Arm/Group Title	Alcohol Dependent Citalopram First Placebo Second	Alcohol Dependent Placebo First Citalopram Second	Healthy Control Citalopram First Placebo Second	Healthy Control Placebo First Citalopram Second
Arm/Group Description	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).	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).	participants with no Axis I mental illness or substance use disorder. Same procedures as AD group	participants with no Axis I mental illness or substance use disorder. Same procedures as AD group
Period Title: Overall Study
Started	5	7	7	7
Completed	4	6	6	4
Not Completed	1	1	1	3
Reason Not Completed
Withdrawal by Subject	0	0	0	1
Physician Decision	1	1	1	2

Baseline Characteristics

Arm/Group Title		Alcohol Dependent	Healthy Control	Total
Arm/Group Description		DSM-IV alcohol dependent	participants with no Axis I illness or substance use disorder	Total of all reporting groups
Overall Number of Baseline Participants		10	10	20
Baseline Analysis Population Description		Patients with alcohol dependence and matched controls were enrolled
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	10 participants	10 participants	20 participants
		38 (7.6)	41 (7.9)	39.5 (7.8)
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	10 participants	10 participants	20 participants
	Female	2 20.0%	5 50.0%	7 35.0%
	Male	8 80.0%	5 50.0%	13 65.0%
		[1] Measure Analysis Population Description: 31 subjects enrolled, only 20 completed the study
Race/Ethnicity, Customized [1]; Measure Type: Count of Participants; Unit of measure: Participants
Race	Number Analyzed	10 participants	10 participants	20 participants
	White	5 50.0%	4 40.0%	9 45.0%
	African American	4 40.0%	5 50.0%	9 45.0%
	Asian	1 10.0%	1 10.0%	2 10.0%
		[1] Measure Analysis Population Description: 31 enrolled, 20 completed the study
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	10 participants	10 participants	20 participants
		10 100.0%	10 100.0%	20 100.0%

Outcome Measures

1. Primary Outcome

Title	Craving for Alcohol in Alcohol Dependence With Citalopram Compared to Placebo
Description	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.
Time Frame	5 minutes after 1 hour of infusion intervention

Outcome Measure Data

Analysis Population Description

All participants completed both arms

Arm/Group Title	Alcohol Dependent Citalopram Infusion	Alcohol Dependent Placebo	Healthy Control Citalopram Infusion	Healthy Control Placebo Infusion
Arm/Group Description:	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.	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.	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.	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.
Overall Number of Participants Analyzed	10	10	10	10
Mean (Standard Deviation); Unit of Measure: score on a scale
	21 (14.6)	30.4 (17.9)	10.8 (4.5)	10.6 (3.7)

2. Secondary Outcome

Title	Striatal Dopamine Receptor Availability in Alcohol Dependence With Citalopram, Compared to Placebo
Description	relative binding potential of dopamine D2/3 receptor specific tracer compared to cerebellum, where there is known to be almost no dopamine receptors.
Time Frame	2-3 hours after 1 hour citalopram or placebo infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Alcohol Dependent Citalopram Infusion	Healthy Control Citalopram Infusion	Alcohol Dependent Placebo Infusion	Healthy Control Placebo Infusion
Arm/Group Description:	DSM-IV alcohol dependent	participants with no Axis I illness or substance use disorder	DSM-IV alcohol dependent	participants with no Axis I illness or substance use disorder
Overall Number of Participants Analyzed	10	10	10	10
Mean (Standard Deviation); Unit of Measure: striatal binding potential ratio
	22.4 (4.0)	25.7 (5.1)	22.5 (3.8)	21.3 (4.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alcohol Dependent Citalopram Infusion, Healthy Control Citalopram Infusion
	Comments	[Not Specified]
	Type of Statistical Test	Equivalence
	Comments	80% power to detect difference p<0.05 two tailed
Statistical Test of Hypothesis	P-Value	0.87
	Comments	ANOVA, uncorrected for MC.
	Method	ANOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.01
	Parameter Dispersion	Type: Standard Deviation; Value: 0.03
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	two weeks of study procedures per participant
Adverse Event Reporting Description	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.
Arm/Group Title	Placebo		Citalopram Infusion
Arm/Group Description	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.		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.
All-Cause Mortality
	Placebo		Citalopram Infusion
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/20 (0.00%)		0/20 (0.00%)
Serious Adverse Events
	Placebo		Citalopram Infusion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0.00%)		0/20 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Placebo		Citalopram Infusion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/20 (35.00%)		12/20 (60.00%)
Gastrointestinal disorders
nausea † [1]	1/20 (5.00%)	1	8/20 (40.00%)	8
dyspepsia † [2]	1/20 (5.00%)	1	0/20 (0.00%)	0
Musculoskeletal and connective tissue disorders
muscle tension †	2/20 (10.00%)	2	2/20 (10.00%)	2
Nervous system disorders
anxiety †	1/20 (5.00%)	1	0/20 (0.00%)	0
dizziness † [3]	2/20 (10.00%)	2	5/20 (25.00%)	5
fatigue †	2/20 (10.00%)	2	7/20 (35.00%)	7
insomnia † [4]	0/20 (0.00%)	0	1/20 (5.00%)	1
† Indicates events were collected by systematic assessment; [1] subjective experience of nausea; [2] stomach upset; [3] temporary dizziness; [4] occurring after study medication given

Limitations and Caveats

A limitation of the study is the modest sample size. Due to the collinearity between smoking and alcohol dependence in the sample, we are also unable to effectively disentangle any specific effect of smoking status on any of the measures reported.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Todd Zorick
• Organization: Harbor-UCLA Department of Psychiatry
• Phone: 310-781-3400
• EMail: tzorick@mednet.ucla.edu

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT01657760 History of Changes
• Other Study ID Numbers: NURA-022-11F; 8331171 ( Other Grant/Funding Number: VA HSR&D )
• First Submitted: July 23, 2012
• First Posted: August 6, 2012
• Results First Submitted: October 30, 2018
• Results First Posted: July 23, 2019
• Last Update Posted: July 23, 2019