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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT01343628
Other study ID # 13464
Secondary ID K01AA015331
Status Terminated
Phase Phase 1
First received April 26, 2011
Last updated May 30, 2012
Start date January 2008
Est. completion date April 2012

Study information

Verified date May 2012
Source University of Virginia
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Terminated
Enrollment 43
Est. completion date April 2012
Est. primary completion date February 2012
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Both
Age group 21 Years to 45 Years
Eligibility 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science


Related Conditions & MeSH terms


Intervention

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
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.

Locations

Country Name City State
United States Center for Addiction Research and Education Charlottesville/ Richmond Virginia

Sponsors (2)

Lead Sponsor Collaborator
University of Virginia National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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). On day 5 of medication No
Secondary Biphasic Alcohol Effects Scale (BAES) On day 5 of medication No
See also
  Status Clinical Trial Phase
Completed NCT01845220 - Prevention of Alcohol Intolerance Phase 2