A Gene by Medication Interaction to the Acute Effects of Alcohol (ATX)

This study has been terminated.
(Terminated due to lack of funding)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Virginia
ClinicalTrials.gov Identifier:
NCT01343628
First received: April 26, 2011
Last updated: May 30, 2012
Last verified: May 2012
  Purpose

Alcohol dependence, or "alcoholism", affects approximately 14 million Americans. Currently, only three pharmacotherapies (disulfiram, naltrexone, and acamprosate) have been approved for the treatment of alcohol dependence and these medications are, at best, moderately successful. Thus, there is a great need for the examination of other biological systems, which contribute/influence the drug reward/addiction pathways within the brain, such that the discovery of new targets and new pharmacotherapies will be possible. Other biological systems in addition to dopamine, such as serotonin, and norepinephrine (NE) are thought to be important in several aspects of addiction, including reward, craving and depression.

This study will examine the effects of a 5 day course of atomoxetine (a selective NE transporter (NET) inhibitor) (80 mg/day; Strattera or placebo) on alcohol-elicited craving and sensitivity to alcohol. The novelty of this study is that of atomoxetine and the fact that it targets NET, neither of which has heretofore been examined in the context of alcohol dependence. It is hopeful that this study, of 64 total individuals, will provide the PI with sufficient preliminary data to submit a subsequent R01 application to study atomoxetine and the involvement of specific single nucleotide polymorphisms within the NET gene on alcohol-related phenotypes in alcohol dependent and non-dependent populations. The long-term objective of this research is to develop more efficacious treatment interventions for alcohol abuse and dependence.


Condition Intervention Phase
Alcohol-induced Cue-craving
Alcohol Sensitivity
Drug: Placebo Comparator
Drug: Active Comparator: Atomoxetine, Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: A Gene by Medication Interaction to the Acute Effects of Alcohol

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • Alcohol urge questionnaire [ Time Frame: On day 5 of medication ] [ Designated as safety issue: No ]
    This questionnaire is used to assess craving. The AUQ consists of eight items related to urge drink that are rated on a 7-point Likert scale with the extremes anchored by "Strongly Disagree" and "Strongly Agree." The AUQ has demonstrated internal consistency and reliability (Bohn et al., 1995).


Secondary Outcome Measures:
  • Biphasic Alcohol Effects Scale (BAES) [ Time Frame: On day 5 of medication ] [ Designated as safety issue: No ]

Enrollment: 43
Study Start Date: January 2008
Study Completion Date: April 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo, Atomoxetine Drug: Placebo Comparator
16 NET SNP rs 11648486 CC and CT individuals will receive placebo and then after one week washout period, receive atomoxetine. Medications will be given as 2 capsules 1x day for 5 days; active atomoxetine groups will receive 40 mg for 3 days, followed by 80 or 120mg (.91-1.4 mg/kg) on days 4 and 5
Active Comparator: Atomoxetine, Placebo Drug: Active Comparator: Atomoxetine, Placebo
16 NET SNP rs 11648486 CC and CT individuals will receive atomoxetine and then after one week washout period, receive placebo.Medications will be given as 2 capsules 1x day for 5 days; active atomoxetine groups will receive 40 mg for 3 days, followed by 80 or 120mg (.91-1.4 mg/kg) on days 4 and 5.

Detailed Description:

Design:

NET genotype groups for rs11648486 SNP (CC 61%; CT 33%; TT 4%) (e.g., C/C and C/T) will be compared to one another in a 2 (NET Genotype: C/C vs. C/T & T/T) x 2 (Medication: atomoxetine 80 mg/day (~ vs. placebo) x 3 (Drink: Drink 1, 2, and 3) mixed factorial repeated measures design using PROC MIXED in SAS by calculating difference scores. Of interest are the possible interactions of the NET SNPs and atomoxetine on cue-elicited craving and the rewarding effects of alcohol across trials.

  Eligibility

Ages Eligible for Study:   21 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Males and females age 21 - 45, as verified upon the presentation of a valid, government issued form of ID
  • Current DSM-IV diagnosis of alcohol dependence using the Mini International Neuropsychiatric Interview (MINI). Which is a shortened form of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders or SCID. The MINI will also be used to exclude patients with other diagnoses.
  • Participants do not meet DSM-IV criteria for any current (i.e., criteria met at any point in the past 30 days) Axis I disorder (including ADHD treated with medication), other than cocaine dependence or those listed above, that warrants treatment or would preclude safe participation in the protocol
  • Not currently take medications that are contraindicated for concurrent use with alcohol;
  • No subjects who have trouble reading the English language or visual or hearing problems that may interfere with the collection of data;
  • No recurring past history of severe hypertension, glaucoma, hyperthyroidism, circulatory disease, hepatitis, chronic liver disease, ulcer disease, seizure disorder, brain disease, cardiac disease, obstructed bowel, or other current treatment of medical conditions that could determine ineligibility;
  • Female subjects must not be breastfeeding and must not be pregnant, as indicated by a pregnancy test that will be conducted immediately prior dispensing of medication.
  • Subjects have to have normal EKGs results
  • Pulse less than 100 beats per minute
  • Participants have to weigh between 125-290; weighing between 125-195 lbs (57 - 88.5 kg)

Exclusion Criteria:

  • Significant medical illness (including severe hypertension) as determined by history and/or complete physical examination. (Note: Presence of mild to moderate chronic diseases not otherwise specifically excluded, that are well controlled by medications/interventions will not be considered clinically significant. However the presence of medical disease that is not well controlled will be considered exclusionary.)
  • tachycardia
  • seizure disorder
  • prior history of myocardial infarction
  • Clinically significant cardiovascular disease that precludes safe participation
  • hepatic or renal impairment; (ie: liver or kidney enzymes > 3x normal limits)
  • pregnant
  • currently using MAO inhibitors within 14 days

    • narrow angle glaucoma
    • currently taking antidepressants or have taken within the last month
    • currently taking pressor agents such as:
    • Alprenolol
    • Carteolol
    • Levobunolol
    • Mepindolol
    • Metipranolol
    • Nadolol
    • Oxprenolol
    • Penbutolol
    • Pindolol
    • Propranolol
    • Sotalol
    • Timolol
    • Acebutolol
    • Atenolol
    • Betaxolol
    • Bisoprolol[16]
    • Esmolol
    • Metoprolol
    • Nebivolol
    • Carvedilol
    • Celiprolol
    • Labetalol
    • Butaxamine
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01343628

Locations
United States, Virginia
Center for Addiction Research and Education
Charlottesville/ Richmond, Virginia, United States, 22903
Sponsors and Collaborators
University of Virginia
Investigators
Principal Investigator: Heather M Haughey, PhD University of Virginia
  More Information

Additional Information:
No publications provided

Responsible Party: University of Virginia
ClinicalTrials.gov Identifier: NCT01343628     History of Changes
Other Study ID Numbers: 13464, K01AA015331
Study First Received: April 26, 2011
Last Updated: May 30, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Virginia:
Alcohol, atomoxetine, Strattera, alcohol dependence, alcoholism

Additional relevant MeSH terms:
Atomoxetine
Adrenergic Uptake Inhibitors
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 26, 2014