fMRI scan study to find out how nalmefene works

Phase 1

• Conditions: almefene (Selincro) is indicated for the reduction of alcohol consumption in adults with alcohol dependence who have a high drinking risk level, without physical withdrawal symptoms and who do not require immediate detoxification.; MedDRA version: 14.1Level: LLTClassification code 10001594Term: Alcohol dependence syndromeSystem Organ Class: 100000004873; Therapeutic area: Psychiatry and Psychology [F] - Behaviours [F01]

• Registration Number: EUCTR2013-001154-98-GB
• Lead Sponsor: H Lundbeck A/S

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-09-02
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 22

Inclusion Criteria

Men aged 20-65 years; drink, on average, at least 7½ units of alcohol daily; have drunk more than 7½ units of alcohol on at least 6 days in the last 4 weeks; willing and able to go without alcohol for one 3-night stay and one 2-night stay on the ward (but participants will have a slow injection of alcohol on each of the 3 full days they spend on the ward); in general good health, as judged by medical history, medical examination, vital signs, ECG and clinical laboratory tests (people who are alcohol-dependent are likely to have increased blood levels of substances linked to liver damage, so people with levels above the upper limit of the normal range for healthy men can be included at the discretion of the investigator); breath alcohol less than 0.02% at screening (when consent is given); able to communicate with study personnel; reliable, willing, and likely to comply with the protocol; willing to comply with the contraception and sperm donation requirements of the protocol; and consent to our informing their GP of their participation in the study, and to our entering their details into the over-volunteering database (TOPS).
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 22
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

We exclude participants who meet the following criteria:

* have had more than 5 alcohol-free days in a row in the last 4 weeks; seeking or receiving treatment for alcohol dependence; have taken part in a support program (such as Alcoholics Anonymous) for alcohol dependence in the last 4 weeks; have taken medicines to treat alcohol dependence in the last 3 months— because participants must be able to tolerate injections of alcohol, and it would be unethical to ask participants seeking treatment for a drinking problem to expose themselves to alcohol;

* at risk of, or has experienced, alcohol withdrawal; poor general health; abuse of drugs; breath alcohol greater than 0.02% at the screening visit; have ever taken medicines to treat ‘fits’ (seizures), type I diabetes, or cancer; have taken certain medicines in the 2 months before the study; have had a serious reaction to any medicine; unable to process certain sugars; have had any condition or operation that might affect the way the body absorbs medicines; have had any clinically significant disease or condition; at risk of suicide; had a major operation within the last 6 months; have taken part in a clinical trial of nalmefene; objection by GP on medical grounds — because they might increase the risk, or confound the assessment of nalmefene; mental illness or intoxication might compromise consent;

* unwilling to comply with the contraception requirements of the protocol — because of the potential risk to babies conceived during the study;

* claustrophobia; any condition which would make it difficult to lie still for very long; metal in the body (eg pacemaker, mechanical heart valve, artificial limb, replacement hip joint, shrapnel); have worked as a metal worker, machinist or welder; have a lot of tattoos — because participants must have 2 fMRI scans during the study;

* employees of HMR, Imanova or the Faculty of Medicine at Imperial College; or close relatives of employees of HMR, Imanova or the Faculty of Medicine at Imperial College — because that is the policy of the sponsor, and to protect the confidentiality of employees; or

* have donated blood, or taken part in another study, within the past 1 month; or don't agree not to donate blood, or take part in another study, during the 1 month after this study — because participants shouldn't expose themselves to unnecessary medicines more often than a few times a year, nor should they donate too much blood;

We’ll study alcohol-dependent participants in good general health who are not seeking or receiving treatment for their drinking because:
* the study medicine is used to treat alcohol dependence
* the study requires participants to tolerate a slow injection of alcohol while lying in a scanner for up to 2 h, and remain alert so that they can complete our tests
* it would be unethical to ask people undergoing or seeking treatment for a drinking problem to expose themselves to alcohol.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: We'll use fMRI (functional magnetic resonance imaging) scans to find out more about where nalmefene acts in the brain and its effects on brain activity.<br><br>The main aim is to find out if nalmefene affects the feeling of reward drinkers get when they have alcohol.<br>;Secondary Objective: In addition to the main aim of the study, there are several exploratory aims. We aim to find out if:<br><br>* nalmefene makes drinkers less likely to act on impulse<br><br>* nalmefene makes drinkers feel less stressed<br><br>* nalmefene affects blood flow in the brain<br><br>We’ll also obtain more information on how much nalmefene gets into the bloodstream, and how quickly the body gets rid of it, after a single dose taken by mouth.;Primary end point(s): Changes in the fMRI response in regions of the brain linked to a reward response (assessed by the monetary incentive delay task);Timepoint(s) of evaluation of this end point: About 4-6 h after dosing.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): There are several exploratory end points:<br><br>*Changes in the fMRI response in regions of the brain linked to impulsive responses (assessed by the Go/NoGo task)<br><br>*Changes in the fMRI response in regions of the brain linked to stress (assessed by the reaction to pictures from the International Affective Picture System)<br><br>*Changes in the blood flow of the brain (assessed by an fMRI technique called arterial spin labelling).<br><br>We’ll also obtain more information on the concentration of the nalmefene in the blood.;Timepoint(s) of evaluation of this end point: fMRI endpoints will be measured about 4-6 h after dosing.<br><br>The concentration of nalmefene in blood will be measured before dosing and frequently up to 24 h after dosing.