Substance DependencePhase 1NCT00908206
Effects of GSK598809 on Brain Activation in Abstinent Alcoholics
A Phase 1 study testing GSK598809 in people with Substance Dependence and Alcohol Dependence, run by GlaxoSmithKline.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Substance Dependence, Alcohol Dependence
- What is being tested?
- GSK598809
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- May 2009to Jul 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
About this study
Official title: A Placebo-controlled, Single-blind, Cross-over, Randomised, fMRI Study Comparing Cue-induced Brain Activation Patterns After a Single Oral Dose of GSK598809 or Placebo in Abstinent Alcoholic Subjects
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.
Read more
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.
Read the detailed description
This is a randomised, placebo controlled, cross-over, single-blind study of the effects of GSK598809 (175 mg, single dose) on multiple pharmacodynamic measures assessed by fMRI and rating scales. In one period subjects will receive GSK598809 and in the other, placebo.
Investigator, subject and all staff at site involved with the study will remain blinded throughout the study. The GSK team will be unblinded to the randomisation code. GSK has classed this as a single blind study however as both investigator and subject are blinded it is referred to as double blind in the study design.
Twenty four recently detoxified and not currently on medication, alcohol-dependent subjects on a specialised addiction ward will be the study group. These subjects will be recruited into this study while participating in a intramural treatment program, outside of the protocol. Subjects will remain in the unit for the duration of the study.
Alcohol-dependent subjects who enter the institutes' treatment program will be screened between 28 and 15 days prior to the first dose of the study medication according to the eligibility criteria. Subjects who satisfy the inclusion and exclusion criteria will be entered into the study. Along with the study procedures described within this protocol, subjects will participate in the institutes standardized inpatient behavioral addiction treatment program outside of the protocol.
Alcohol-dependent participants have to fulfil diagnostic criteria of alcohol dependence as detailed in the eligibility criteria. The severity of alcoholism will be assessed with the Alcohol Dependence Scale and the amount of lifetime alcohol intake will be measured with Lifetime Drinking History.
After the final alcoholic drink and prior to the first dose of study medication subjects will be treated with detoxification medication (lorazepam) for withdrawal symptoms for up to seven days. Following the treatment of withdrawal symptoms, subjects will have a medication free period for at least seven days to ensure the detoxification medication has been washed out. Liver function tests will be performed again at Day -1 of each dosing day and must be in line with criteria.
Subjects will be randomised to one of two sequence: Placebo received first followed by GSK598809, or GKS598809 received first followed by Placebo. Between 8 and 14 days after the last dose of withdrawal medication, subjects will have their first dose of study medication and first MRI scan. At least 7 days and less than 10 days after the first dose/scanning day subjects will receive their second dosing and their second MRI scan.
All subjects will undergo the following battery of minimal risk procedures during the study; filling out questionnaires, performing agreed behavioural tasks, scanning procedures including fMRI and structural MRI (baseline). Alcohol abstinence will be confirmed by random alcohol-breath tests.
Craving for alcohol will be measured with the Alcohol Urge Questionnaire (AUQ) and the Obsessive Compulsive Drinking Scale (OCDS) before each fMRI scanning session and the Alcohol Craving Questionnaire before and after each fMRI scanning session. Nicotine consumption will be assessed with the Fagerstrom Test for nicotine dependence both at screening and on the day prior to each dosing day.
As described above subjects will undergo two MRI scanning sessions of about 1h (1.5h maximum) each, at intervals of at least one week. The scanning will take place after the administration of study medication (GSK598809 or placebo). The single dose of GSK598809 or placebo will be administered about 1-2 h prior to the scan.
The MRI scanning session will start with acquisition of structural MRI brain images to be used as an anatomical reference. The acquisition of the structural MRI will last for around 6 minutes and during this time subjects are able to get familiar with the MRI procedure. Fear and arousal will decline slowly after the first minutes and prior to the fMRI paradigms. Three fMRI paradigms have been selected to probe reactivity to alcohol-related cues, monetary reward, and to measure BOLD signal fluctuations in the brain resting state. Subjects will be discharged from the inpatient unit 2 days (48 hours) after the second fMRI scan; they will be motivated to remain abstinent and returned to their previous living situation.
- Conditions
- Substance Dependence, Alcohol Dependence
- Being tested
- GSK598809
- Keywords
- Alcoholism, Craving, Dependence, Alcohol
- Medical subject headings
- Substance-Related Disorders, Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK598809Drug
Subjects will receive a single 175 mg oral dose of GSK598809.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo to match GSK598809. Receives: Drug: GSK598809 |
What is being measured
The primary outcome is the main question the study is designed to answer.
BOLD signal changes in the relevant brain areas following presentation of visual alcohol-related vs neutral, non-alcohol related cues.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: Throughout study.
Pharmacokinetic parameters of GSK598809 and its metabolite GSK685249: AUC (0-∞), Cmax, tmax, t½.
Measured: 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.
Measured: 1.5h (± 0.5h) after each dose (2 doses)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2009 (estimated)
- Study startMay 2009
- Primary completionJul 2009
- Study completionJul 2009
Why it stopped: Study not approved by BfARM
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Substance DependenceStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00908206
- Sponsor's protocol ID
- 109709
- Status last verified
- Apr 2015
- First submitted
- 21 May 2009
- Last updated
- 17 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Placebo-controlled, Single-blind, Cross-over, Randomised, fMRI Study Comparing Cue-induced Brain Activation Patterns After a Single Oral Dose of GSK598809 or Placebo in Abstinent Alcoholic Subjects
- ClinicalTrials.gov ID
- NCT00908206
- Acronym / sponsor ID
- 109709
- Conditions
- Substance Dependence, Alcohol Dependence
- Keywords
- Alcoholism, Craving, Dependence, Alcohol
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study not approved by BfARM
- Enrolment
- 0 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- May 2009
- Primary completion
- Jul 2009 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 25 May 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a randomised, placebo controlled, cross-over, single-blind study of the effects of GSK598809 (175 mg, single dose) on multiple pharmacodynamic measures assessed by fMRI and rating scales. In one period subjects will receive GSK598809 and in the other, placebo.
Investigator, subject and all staff at site involved with the study will remain blinded throughout the study. The GSK team will be unblinded to the randomisation code. GSK has classed this as a single blind study however as both investigator and subject are blinded it is referred to as double blind in the study design.
Twenty four recently detoxified and not currently on medication, alcohol-dependent subjects on a specialised addiction ward will be the study group. These subjects will be recruited into this study while participating in a intramural treatment program, outside of the protocol. Subjects will remain in the unit for the duration of the study.
Alcohol-dependent subjects who enter the institutes' treatment program will be screened between 28 and 15 days prior to the first dose of the study medication according to the eligibility criteria. Subjects who satisfy the inclusion and exclusion criteria will be entered into the study. Along with the study procedures described within this protocol, subjects will participate in the institutes standardized inpatient behavioral addiction treatment program outside of the protocol.
Alcohol-dependent participants have to fulfil diagnostic criteria of alcohol dependence as detailed in the eligibility criteria. The severity of alcoholism will be assessed with the Alcohol Dependence Scale and the amount of lifetime alcohol intake will be measured with Lifetime Drinking History.
After the final alcoholic drink and prior to the first dose of study medication subjects will be treated with detoxification medication (lorazepam) for withdrawal symptoms for up to seven days. Following the treatment of withdrawal symptoms, subjects will have a medication free period for at least seven days to ensure the detoxification medication has been washed out. Liver function tests will be performed again at Day -1 of each dosing day and must be in line with criteria.
Subjects will be randomised to one of two sequence: Placebo received first followed by GSK598809, or GKS598809 received first followed by Placebo. Between 8 and 14 days after the last dose of withdrawal medication, subjects will have their first dose of study medication and first MRI scan. At least 7 days and less than 10 days after the first dose/scanning day subjects will receive their second dosing and their second MRI scan.
All subjects will undergo the following battery of minimal risk procedures during the study; filling out questionnaires, performing agreed behavioural tasks, scanning procedures including fMRI and structural MRI (baseline). Alcohol abstinence will be confirmed by random alcohol-breath tests.
Craving for alcohol will be measured with the Alcohol Urge Questionnaire (AUQ) and the Obsessive Compulsive Drinking Scale (OCDS) before each fMRI scanning session and the Alcohol Craving Questionnaire before and after each fMRI scanning session. Nicotine consumption will be assessed with the Fagerstrom Test for nicotine dependence both at screening and on the day prior to each dosing day.
As described above subjects will undergo two MRI scanning sessions of about 1h (1.5h maximum) each, at intervals of at least one week. The scanning will take place after the administration of study medication (GSK598809 or placebo). The single dose of GSK598809 or placebo will be administered about 1-2 h prior to the scan.
The MRI scanning session will start with acquisition of structural MRI brain images to be used as an anatomical reference. The acquisition of the structural MRI will last for around 6 minutes and during this time subjects are able to get familiar with the MRI procedure. Fear and arousal will decline slowly after the first minutes and prior to the fMRI paradigms. Three fMRI paradigms have been selected to probe reactivity to alcohol-related cues, monetary reward, and to measure BOLD signal fluctuations in the brain resting state. Subjects will be discharged from the inpatient unit 2 days (48 hours) after the second fMRI scan; they will be motivated to remain abstinent and returned to their previous living situation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: GSK598809Placebo to match GSK598809. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK598809Subjects will receive a single 175 mg oral dose of GSK598809. | Drug | Placebo |
Primary outcome
BOLD signal changes in the relevant brain areas following presentation of visual alcohol-related vs neutral, non-alcohol related cues.
Time frame: 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.
Time frame: 1.5h (± 0.5h) after each dose (2 doses)
4 secondary outcomes
Subjective craving in response to alcohol-related cues measured with the Alcohol Urge Questionnaire (AUQ) and the Obsessive Compulsive Drinking Scale (OCDS).
Time frame: 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.
Time frame: Throughout study.
Pharmacokinetic parameters of GSK598809 and its metabolite GSK685249: AUC (0-∞), Cmax, tmax, t½.
Time frame: 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.
Time frame: 1.5h (± 0.5h) after each dose (2 doses)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK598809 in people with Substance Dependence and Alcohol Dependence, run by GlaxoSmithKline.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 17 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
BOLD signal changes in the relevant brain areas following presentation of visual alcohol-related vs neutral, non-alcohol related cues. (time frame: 1.5h (± 0.5h) after each dose (2 doses)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2015.