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

This study is currently recruiting participants.
Verified April 2014 by Department of Veterans Affairs
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT01657760
First received: July 23, 2012
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

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 OEF/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.


Condition Intervention Phase
Alcohol Dependence
Drug: citalopram
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Citalopram Effects on Craving and Dopamine Receptor Availability in Alcoholics

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Craving for alcohol in type B alcohol dependence with citalopram compared to placebo [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
    To assess whether craving for alcohol in type B alcohol dependence is affected by iv citalopram, compared to placebo.


Secondary Outcome Measures:
  • Striatal dopamine receptor availability in type B alcohol dependence with citalopram, compared to placebo [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
    To assess whether striatal dopamine receptor availability in type B alcohol dependence is affected by iv citalopram, compared to placebo.


Estimated Enrollment: 60
Study Start Date: April 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Arm 1
Intravenous citalopram, 40 mg vs. saline control, in a double-blind, crossover study, with infusion days at least 2 weeks apart.
Active Comparator: citalopram infusion
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
citalopram, 40 mg IV, vs. saline control, each to be administered in a double-blinded, within-subjects design.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   21 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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 TLFB.

Exclusion Criteria:

Exclusion criteria for Alcohol Dependence:

  • 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.

Exclusion criteria for Healthy Controls:

  • 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.

Exclusion criteria for all subjects:

  • 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, ALT, 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;
  • Presence of metal fragments, pacemaker, or other ferromagnetic material which would prevent safe completion of an MRI scan;
  • Recent history of radiation exposure which would make exposure to radiation from serial PET scans contraindicated;
  • Non-zero breath-alcohol level on screening. We will exclude participants who present to study appointments intoxicated, as active alcohol intoxication may interact unpredictably with citalopram and produce unreliable results in assessments of mood or alcohol craving (e.g. Ray and Hutchison, 2007; Ray et al., 2011; see preliminary data C.2. above);
  • Resting vital signs on any study visit outside of acceptable parameters: Pulse of 50-105 bpm, Blood pressures of 90-160 mm Hg systolic, 55-100 mm Hg diastolic;
  • Any indication of suicidal ideation (i.e. as assessed by question 9 on the BDI-II), or elevated index of depressive symptoms, as evidenced by BDI-II score of 20;
  • Presence in the body of a metal device (e.g., pacemaker, infusion pump, aneurysm clip, metal prosthesis or plate) that could either interfere with the acquis
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01657760

Contacts
Contact: Todd S Zorick, MD PhD Todd.Zorick@va.gov
Contact: Arthur L Brody, MD arthur.brody@va.gov

Locations
United States, California
VA Greater Los Angeles Healthcare System, West Los Angeles, CA Recruiting
West Los Angeles, California, United States, 90073
Contact: Todd S Zorick, MD PhD       Todd.Zorick@va.gov   
Contact: Arthur L Brody, MD       arthur.brody@va.gov   
Principal Investigator: Todd S. Zorick, MD PhD         
Sponsors and Collaborators
Investigators
Principal Investigator: Todd S. Zorick, MD PhD VA Greater Los Angeles Healthcare System, West Los Angeles, CA
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT01657760     History of Changes
Other Study ID Numbers: NURA-022-11F, 8331171
Study First Received: July 23, 2012
Last Updated: April 9, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Department of Veterans Affairs:
craving
dopamine
citalopram
ssri

Additional relevant MeSH terms:
Alcoholism
Alcohol-Related Disorders
Substance-Related Disorders
Mental Disorders
Citalopram
Dexetimide
Dopamine
Dopamine Agents
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Physiological Effects of Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Cardiotonic Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on April 22, 2014