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Phase 1 N=26 Randomized Double-blind Basic Science

Citalopram Effects on Craving and Dopamine Receptor Availability in Alcoholics

Alcohol Dependence

Enrolled (actual)
26
Serious AEs
0.0%
Results posted
Jul 2019
Primary outcome: Primary: Craving for Alcohol in Alcohol Dependence With Citalopram Compared to Placebo — 21; 30.4; 10.8; 10.6 score on a scale

Study Design & Population

Study type
Interventional
Phase
Phase 1
Interventions
citalopram (Drug)
Age
Adult · 21+ yrs
Sex
All
Sponsor
VA Office of Research and Development
Primary completion
Aug 2017

Outcome Measures

OutcomeResultp-value
PRIMARY
Craving for Alcohol in Alcohol Dependence With Citalopram Compared to Placebo
21; 30.4; 10.8; 10.6
SECONDARY
Striatal Dopamine Receptor Availability in Alcohol Dependence With Citalopram, Compared to Placebo
22.4; 25.7; 22.5; 21.3 0.87

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.

Eligibility 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 Timeline Followback Method (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 ( 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;
  • 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 Beck Depression Inventory-II [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 acquisition of the MRI scan of the brain or for whom the MRI scan would pose a potential risk will
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01657760). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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