Citalopram Effects on Craving and Dopamine Receptor Availability in Alcoholics

NCT01657760 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: NURA-022-11F8331171
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Alcohol use disorders (AUDs) are highly prevalent among U.S. civilians, and even more prevalent in the U.S. Veteran population. AUDs are frequently co-morbid with depressive symptoms in psychiatric clinical populations, resulting in an increased severity of both conditions. Indeed, returning Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) Veterans have extraordinarily high rates of alcohol misuse and co-morbid psychiatric symptoms, indicating that future Veteran clinical populations will be particularly affected by AUDs. While FDA-approved medications are available to treat AUDs, their efficacy is low compared to available psychosocial treatments. Despite the lack of evidence for efficacy from controlled trials, antidepressants are frequently prescribed to clinical populations (including Veterans) with active AUDs. A better understanding of patient-level clinical variables that may confer poor response to treatment with antidepressants would allow clinicians better tools to distinguish those alcohol-dependent Veterans likely to do worse with antidepressant treatment.

Conditions

Alcohol Dependence

Keywords

craving; dopamine; citalopram; ssri

Outcome Measures

Primary Outcomes (1)

• Craving for Alcohol in Alcohol Dependence With Citalopram Compared to Placebo

  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.

  5 minutes after 1 hour of infusion intervention

Secondary Outcomes (1)

• Striatal Dopamine Receptor Availability in Alcohol Dependence With Citalopram, Compared to Placebo

  2-3 hours after 1 hour citalopram or placebo infusion

Study Arms (2)

placebo

PLACEBO COMPARATOR

Intravenous saline control, in a double-blind, crossover study, with infusion days at least 2 weeks apart.

Drug: citalopram

citalopram infusion

ACTIVE COMPARATOR

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.

Drug: citalopram

Interventions

citalopram DRUG

citalopram, 40 mg IV, vs. saline control, each to be administered in a double-blinded, within-subjects design.

citalopram infusion; placebo

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Must be U.S. Veteran
• Alcohol Dependence:
• Age between 21 and 55;
• Meeting DSM-IV diagnostic criteria for alcohol dependence;
• Report drinking at least 48 standard drinks in a 30-day period, during the 90 days before enrollment, and
• Must have had at least 2 days of heavy drinking (at least 5 drinks/day for men, 4 drinks/day for women) in the last 30 days
• Healthy Control:
• Age between 21 and 55;
• No Axis I DSM-IV diagnosis (except for nicotine dependence);
• Report drinking less than 10 drinks weekly over the past 90 days prior to study entry by Timeline Followback Method (TLFB).

You may not qualify if:

• Current treatment for alcohol problems or a history of treatment in the 30 days before enrollment or are treatment seeking;
• A current (last 12 months) DSM-IV diagnosis of dependence on any psychoactive substances other than alcohol and nicotine.
• Any history of treatment for alcohol or other substance use disorders;
• Any history of DSM-IV diagnosis of dependence on any psychoactive substances other than nicotine;
• Any history of DSM-IV diagnosis of Axis I mental illness.
• A current (last 12 months) DSM-IV diagnosis of schizophrenia, bipolar disorder, other psychotic disorder, eating disorder, panic disorder with or without agoraphobia;
• Current use of psychoactive drugs, other than occasional marijuana use (\< 3 uses per week), as determined by a positive urine screen for narcotics, amphetamines, or sedative hypnotics;
• Serious alcohol withdrawal symptoms as indicated by a score \> 10 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA);
• Clinically significant physical abnormalities as indicated by physical examination, hematological laboratory assay, or urinalysis, defined as: hematology and chemistry laboratory tests that are within normal (+/- 10%) limits with the following exceptions: a) liver function tests (total bilirubin, alanine transaminase \[ALT\], aspartate aminotransferase \[AST\], and alkaline phosphatase) \< 3 x the upper limit of normal, and b) kidney function tests (creatinine and BUN) \< 2 x the upper limit of normal;
• A screening ECG that demonstrates anything other than normal sinus rhythm, normal conduction, and no clinically significant arrhythmias;
• History of epilepsy, seizures, or severe head trauma;
• History of alcohol intoxication delirium, alcohol withdrawal delirium or seizure, alcohol-induced persisting dementia, or alcohol-induced psychosis;
• Treatment with any of the following medications within the last 30 days prior to randomization: antidepressants, anti-convulsants, hypnotics, antipsychotics, psychomotor stimulants, or anti-anxiety agents;
• Previous treatment with citalopram discontinued due to an adverse event;
• Pregnancy, nursing, or refusal to use reliable barrier method of birth control, if female;

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

West Los Angeles, California, 90073, United States

Location

Related Publications (1)

• Zorick T, Okita K, Renard KB, Mandelkern MA, Brody AL, London ED. The Effects of Citalopram and Thalamic Dopamine D2/3 Receptor Availability on Decision-Making and Loss Aversion in Alcohol Dependence. Psychiatry J. 2022 Sep 20;2022:5663274. doi: 10.1155/2022/5663274. eCollection 2022.

  PMID: 36249526 DERIVED

MeSH Terms

Conditions

Alcoholism

Interventions

Citalopram

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

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.

Results Point of Contact

• Title: Todd Zorick
• Organization: Harbor-UCLA Department of Psychiatry

tzorick@mednet.ucla.edu

310-781-3400

Study Officials

• Todd S Zorick, MD PhD

  VA Greater Los Angeles Healthcare System, West Los Angeles, CA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2012
• First Posted: August 6, 2012
• Study Start: May 1, 2014
• Primary Completion: August 31, 2017
• Study Completion: September 1, 2017
• Last Updated: July 23, 2019
• Results First Posted: July 23, 2019

Record last verified: 2019-07

Locations

US (1)