search
Back to results

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

Primary Purpose

Alcohol-induced Cue-craving, Alcohol Sensitivity

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Placebo Comparator
Active Comparator: Atomoxetine, Placebo
Sponsored by
University of Virginia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Alcohol-induced Cue-craving focused on measuring Alcohol, atomoxetine, Strattera, alcohol dependence, alcoholism

Eligibility Criteria

21 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Center for Addiction Research and Education

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo, Atomoxetine

Atomoxetine, Placebo

Arm Description

Outcomes

Primary Outcome Measures

Alcohol urge questionnaire
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)

Full Information

First Posted
April 26, 2011
Last Updated
May 30, 2012
Sponsor
University of Virginia
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
search

1. Study Identification

Unique Protocol Identification Number
NCT01343628
Brief Title
A Gene by Medication Interaction to the Acute Effects of Alcohol
Acronym
ATX
Official Title
A Gene by Medication Interaction to the Acute Effects of Alcohol
Study Type
Interventional

2. Study Status

Record Verification Date
May 2012
Overall Recruitment Status
Terminated
Why Stopped
Terminated due to lack of funding
Study Start Date
January 2008 (undefined)
Primary Completion Date
February 2012 (Actual)
Study Completion Date
April 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Virginia
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol-induced Cue-craving, Alcohol Sensitivity
Keywords
Alcohol, atomoxetine, Strattera, alcohol dependence, alcoholism

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
43 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo, Atomoxetine
Arm Type
Placebo Comparator
Arm Title
Atomoxetine, Placebo
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Placebo Comparator
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Active Comparator: Atomoxetine, Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Alcohol urge questionnaire
Description
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).
Time Frame
On day 5 of medication
Secondary Outcome Measure Information:
Title
Biphasic Alcohol Effects Scale (BAES)
Time Frame
On day 5 of medication

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Heather M Haughey, PhD
Organizational Affiliation
University of Virginia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Addiction Research and Education
City
Charlottesville/ Richmond
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States

12. IPD Sharing Statement

Learn more about this trial

A Gene by Medication Interaction to the Acute Effects of Alcohol

We'll reach out to this number within 24 hrs