Effects of GSK598809 on Brain Activation in Abstinent Alcoholics

NCT00908206 | Withdrawn Phase 1

• 1 other identifier: 109709
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will compare the effects of GSK598809 and placebo in alcohol dependent volunteers. A placebo is a pill with no drug in it (i.e. dummy drug) but it is made to look exactly like the real drug. Subjects will be given one dose of GSK598809 during one visit and placebo during the other visit. These dosing visits will be at least 1 week apart. The study is randomised, which means that a computer programme will decide by chance (like tossing a coin), the order in which subjects will receive GSK598809 or the placebo, or in other words, whether they will receive GSK598809 or placebo first. The study is blinded, which means the subjects will not know whether they are receiving study drug or placebo first and neither will the doctors at the institute. If necessary for reasons of safety, the study staff can find out exactly what the subject has received. The study will last for approximately 4 weeks but could be up to 6 weeks, depending on length of time between screening and dosing. From screening the subjects will be alcohol-abstinent, they may be put on medication for treatment of withdrawal symptoms and then will have at least 7 days without any medication before beginning the study medication. During the study the subjects will be inpatients at the Central Institute of Mental Health. All subjects will be required to fill out questionnaires, perform behavioural tasks and undergo MRI and functional MRI (fMRI) scans.

Conditions

Substance Dependence; Alcohol Dependence

Keywords

Alcoholism; Craving; Dependence; Alcohol

Outcome Measures

Primary Outcomes (2)

• BOLD signal changes in the relevant brain areas following presentation of visual alcohol-related vs neutral, non-alcohol related cues.

  1.5h (± 0.5h) after each dose (2 doses)

• BOLD signal changes in the same brain structures and circuits as above during a Monetary Incentive Delay task.

  1.5h (± 0.5h) after each dose (2 doses)

Secondary Outcomes (4)

• Subjective craving in response to alcohol-related cues measured with the Alcohol Urge Questionnaire (AUQ) and the Obsessive Compulsive Drinking Scale (OCDS).

  Screening and pre-scan.

• Spontaneously reported adverse events, laboratory values, cardiovascular variables (blood pressure, heart rate, and ECG variables), temperature, respiratory rate, serum prolactin concentrations, TSH, testosterone, LH and FSH.

  Throughout study.

• Pharmacokinetic parameters of GSK598809 and its metabolite GSK685249: AUC (0-∞), Cmax, tmax, t½.

  Pre-dose to 48h post dose.

• Pair-wise correlation of BOLD signal changes in different image voxels and between selected brain structures during the alcohol-related cue paradigm and the Monetary Incentive Delay task, and in the brain resting state.

  1.5h (± 0.5h) after each dose (2 doses)

Study Arms (1)

Placebo

PLACEBO COMPARATOR

Placebo to match GSK598809.

Drug: GSK598809

Interventions

GSK598809 DRUG

Subjects will receive a single 175 mg oral dose of GSK598809.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Alcohol dependent for at least 2 years.
• Willing to use appropriate contraception method.
• Weight less than 120 kg.
• BMI within the range 18.5 - 33 kg/m2.

You may not qualify if:

• Heavy smokers (more than 25 cigarettes per day).
• Liver cirrhosis.
• Pregnant or breast feeding female.
• Psychiatric disorder.
• Substance dependence or abuse other than alcoholism and nicotine dependence.
• Medical illness.
• ECG abnormality (personal or family history).
• Sudden unexplained death or syncope in first degree relative.

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Conditions

Substance-Related Disorders; Alcoholism

Interventions

GSK598809

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders; Alcohol-Related Disorders

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 21, 2009
• First Posted: May 25, 2009
• Study Start: May 1, 2009
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: April 17, 2015

Record last verified: 2015-04