Effects of the D3 Antagonist GSK598809 on Food Reward and Reinforcement

A Single-blind, Randomized, Placebo Controlled, Two-period Crossover fMRI Study to Investigate the Effects of the D3 Antagonist GSK598809 on Neural and Behavioural Responses to Food Reward and Reinforcement After a Single Oral Dose of GSK598809 in Overweight and Obese Subjects.

This novel compound is a new experimental treatment that may help people to stop compulsive overeating. Compulsive overeating or binge eating is one of the main reasons why people are overweight or obese. Recent research has shown that some kinds of overeating may be linked to a brain chemical called dopamine. There is some evidence that blocking the action of this chemical in animals can reduce food intake, particularly of foods that are high in fat and sugar. The purpose of this study is to find out if this compound (which blocks the effects of dopamine) has the same effect in overweight or obese people, as it does in animals.

Study Overview

• Status: Completed
• Conditions: Substance Dependence
• Intervention / Treatment: Drug: GSK598809 Placebo Capsules; Drug: GSK598809 Capsules

Detailed Description

This novel compound is being developed for the treatment of substance dependence and potentially other impulse control disorders.

This is an fMRI study designed to examine the behavioural and physiological effects of a single dose of novel compound on food reward and reinforcement in relation to food seeking behaviour under conditions of fasting, using fMRI, neurocognitive and metabolic endpoints in overweight and obese subjects. These main objectives will be evaluated in the principal part of the study, Part A. The study will also consist of a follow up period of weight management with a dietician where exploratory objectives are considered, Part B.

Part A, will be a single-blind, randomised, placebo controlled, multi-centre, two-period cross-over study. Approximately 24 subjects will be enrolled such that a minimum of 20 subjects complete dosing and critical assessments. All subjects will be required to complete questionnaires, perform a series of behavioural tasks and scanning procedures. Safety and tolerability will be assessed by monitoring subjects for adverse events, vital signs, ECGs, movement disorders (EPS, Akathisia) and laboratory parameters. The pharmacokinetic profile of the compound in this subject population will be determined by blood sampling over a 72 hour period post dosing, in both sessions. Part B will consist of 12 weeks weight management directed by a dietician on an outpatient basis. Subjects will have fortnightly visits with a dietician and at the end of the 12 weeks complete three questionnaires (TFEQ-18R, DBEQ and YBOCS-BE) and have their weight measured to assess weight loss.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, NW10 7EW
    • GSK Investigational Site
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• generally healthy
• right handed
• binge eating episode
• use appropriate contraception method
• willing to see a dietician
• overweight or obese (BMI 27 - 40 kg/m2)

Exclusion Criteria:

• pregnant or breast feeding female
• recent weight loss or gain
• recent use of weight loss drugs
• surgery for obesity
• abuse alcohol or drugs
• cannot do MRI scans
• smokers
• certain emotional problems being treated with medications
• medical, surgical or neuropsychiatric illness
• ECG abnormality
• sudden unexplained death or syncope in first degree relatives

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 2 way cross over.	Drug: GSK598809 Placebo Capsules; Treatment of substance dependence and potentially other impulse control disorders.
Active Comparator: Active; 2 Way cross over	Drug: GSK598809 Capsules; GSK598809 is being developed for the treatment of substance dependence and potentially other impulse control disorders.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Functional MRI: Food Processing Task, Food-Stop Signal Task, Food Stroop Task	9 weeks
Behavioural Neurocognitive Task: Visual Probe Task, Stimulus Response Compatibility Task, Pavlovian-Instrumental Task.	9 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Appetite VAS, Bond and Lader VAS, Distress VAS, BIS II, TFEQ, BIS/BAS, BDI-II, Body weight, Metabolic markers: plasma leptin, ghrelin, alpa MSH	9 weeks
PK endpoints: AUC, Cmax, tmax, t1/2	9 weeks
Safety and tolerability: adverse events, laboratory values, cardiovascular - blood pressure; heart rate; ECGs, movement disorders, temperature, respiratory rate, serum prolactin, GH and TSH	9 weeks

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2008
• Primary Completion (Actual): April 26, 2010
• Study Completion (Actual): April 26, 2010

Study Registration Dates

• First Submitted: December 10, 2009
• First Submitted That Met QC Criteria: December 23, 2009
• First Posted (Estimate): December 25, 2009

Study Record Updates

• Last Update Posted (Actual): June 20, 2017
• Last Update Submitted That Met QC Criteria: June 16, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Overweight; Obese; fMRI; Cognition; Behaviour; Food Reinforcement; Food Reward; Food Addiction; Metabolic endpoints
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders
• Other Study ID Numbers: 109710

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 109710
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 109710
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Informed Consent Form
   Information identifier: 109710
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Study Protocol
   Information identifier: 109710
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 109710
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Statistical Analysis Plan
   Information identifier: 109710
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register