AlcoholismEarly Phase 1NALCUENCT02372318
Single-dose of Nalmefene to Modulate Neural Alcohol Cue Reactivity
A Early Phase 1 study testing Nalmefene in people with Alcoholism, run by Central Institute of Mental Health, Mannheim at 1 site in Germany.
Trial summary
The aim of this study is to use functional Magnetic Resonance Imaging (fMRI) to measure neural reactivity to alcohol-related and emotional cues in alcohol dependent subjects following a single dose of the opioid receptor modulator nalmefene. The study will be done in a cross over design with nalmefene versus placebo. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Alcoholism
- What is being tested?
- Nalmefene
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteGermany
- Study dates
- Apr 2015to May 2016
- Phase
- Early 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
- severe alcohol use disorder according to DSM 5 and "heavy drinking": alcohol consumption >=60g (men) and >=40g (women) (minimum of 5 days / week)
- right-handedness
- normal or corrected to normal vision
- signed written informed consent
Who cannot join
- valid at the time of MRI investigation:
- psychotropic medication within the last 14 days
- severe withdrawal symptoms (CIWA-Ar > 4; Sullivan et al. 1989)
- intoxication (breath alcohol concentration > 0.3 ‰)
- common exclusion criteria for MRI (e.g. metal, claustrophobia)
- positive drug screening (opioids, cannabinoids, benzodiazepines, barbiturates, cocaine, amphetamines)
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- pregnancy
- contraindications to the prescription of nalmefene valid at inclusion:
- previous severe withdrawal / withdrawal complications
- previous inpatient detoxification treatment
- other Axis I psychiatric diagnoses than alcohol- or nicotine-dependence in the last 12 months
- neurological disorders, history of brain injury
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Nalmefene Challenge to Modulate Neural Reactivity to Alcohol-related and Emotional Cues in Non-treatment Seeking Alcohol Dependent Participants
The aim of this study is to use functional Magnetic Resonance Imaging (fMRI) to measure neural reactivity to alcohol-related and emotional cues in alcohol dependent subjects following a single dose of the opioid receptor modulator nalmefene. The study will be done in a cross over design with nalmefene versus placebo.
Read the detailed description
All subjects will undergo a battery of minimal risk procedures during each study visit; filling out questionnaires, performing agreed behavioral tasks, scanning procedures including two functional MRI (fMRI) scans as well as structural MRI.
The fMRI will be obtained in non-abstinent participants with breath alcohol concentrations not larger than > 0.3 ‰ and withdrawal severity not more than 4 on the clinical institute withdrawal assessment for alcohol (CIWA-Ar) scale.
Alcohol consumption will be assessed with the Form90 interview. Severity of alcohol dependence will be examined with the Alcohol Dependence Scale (ADS). Drinking situations will be assessed with the Inventory of Drinking Situations (IDS). Trait aspects of craving for alcohol will be measured with the Obsessive Compulsive Drinking Scale (OCDS). To examine state and trait anxiety the State-Trait Anxiety Inventory (STAI) will be used. Depressive symptoms will be measured with the Beck Depression Inventory (BDI) and the State-Trait Depression Scales (STDS). Nicotine consumption will be assessed with the Fagerström Test for Nicotine Dependence.
The following scales will be administered before and after each fMRI scanning: The Alcohol Craving Questionnaire (ACQ), the Alcohol Urge Questionaire (AUQ) and visual analogue scales for craving assessment.
Participants will undergo two fMRI scanning sessions at intervals of one week: one 2 h after administration of nalmefene and one 2 h after administration of placebo, carried out in a randomized order.
MRI examinations include
- a cue-reactivity task;
- an emotional faces task;
- resting-state fMRI;
- structural MRI;
- including preparation, instructions and breaks
- Conditions
- Alcoholism
- Being tested
- Nalmefene, Placebo
- Keywords
- opiod receptor modulator nalmefene, cue-reactivity, fMRI, resting-state networks
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NalmefeneDrug
Also called Selincro
18mg of Nalmefen will be administered orally
PlaceboDrug
Placebo tablet
| Study group | Role | What they receive |
|---|---|---|
| Nalmefene Challenge | Experimental | Participants will receive 18mg Nalmefene two hours prior to fMRI measurement. During fMRI scanning alcohol cues will be presented. Receives: Drug: Nalmefene |
| Placebo | Placebo comparator | Participants will receive Placebo two hours prior to fMRI measurement. During fMRI scanning alcohol cues will be presented. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in cue-induced brain activation between two fMRI scans (randomization to an intake of nalmefene (18 mg) or placebo).
This difference will be extracted from whole-brain contrast images in the VS and DS using the percentage of activated voxels in these regions of interest (ROI).
Measured: Primary outcome measures will be assessed on day 2 and day3 after fMRI scan, data collection will take up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2015 (estimated)
- Study startApr 2015
- Primary completionMay 2016
- Study completionMay 2016
Why it stopped: Anticipated nr of 25 probands was not reached in terms of full data sets (missing data, low fMRI data quality), but time frame for recruitment ended.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AlcoholismStudies of the same condition, open and under way.
- 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Central Institute of Mental Health, Mannheim
- Sponsor type
- University, hospital or other
- Collaborators
- Lundbeck GmbH, Ericusspitze 2, 20457 Hamburg
- Responsible party
- Sponsor
- Investigators
- Sabine Vollstädt-Klein, Prof. Dr., Principal investigator, Central Institute of Mental Health, MannheimFalk Kiefer, Prof. Dr., Principal investigator, Central Institute of Mental Health, Mannheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02372318
- Sponsor's protocol ID
- 37
- Acronym
- NALCUE
- Status last verified
- Jan 2016
- First submitted
- 6 Feb 2015
- Last updated
- 2 Jul 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Grundinger N, Gerhardt S, Karl D, Mann K, Kiefer F, Vollstadt-Klein S. The effects of nalmefene on the impulsive and reflective system in alcohol use disorder: A resting-state fMRI study. Psychopharmacology (Berl). 2022 Aug;239(8):2471-2489. doi: 10.1007/s00213-022-06137-1. Epub 2022 Apr 15.
PubMed 35426492
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nalmefene Challenge to Modulate Neural Reactivity to Alcohol-related and Emotional Cues in Non-treatment Seeking Alcohol Dependent Participants
- ClinicalTrials.gov ID
- NCT02372318
- Acronym / sponsor ID
- NALCUE / 37
- Conditions
- Alcoholism
- Keywords
- opiod receptor modulator nalmefene, cue-reactivity, fMRI, resting-state networks
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Anticipated nr of 25 probands was not reached in terms of full data sets (missing data, low fMRI data quality), but time frame for recruitment ended.
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Central Institute of Mental Health, MannheimUniversity, hospital or other
- Collaborators
- Lundbeck GmbH, Ericusspitze 2, 20457 Hamburg
- Study start
- Apr 2015
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 26 Feb 2015 (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.
The aim of this study is to use functional Magnetic Resonance Imaging (fMRI) to measure neural reactivity to alcohol-related and emotional cues in alcohol dependent subjects following a single dose of the opioid receptor modulator nalmefene. The study will be done in a cross over design with nalmefene versus placebo.
Detailed description
All subjects will undergo a battery of minimal risk procedures during each study visit; filling out questionnaires, performing agreed behavioral tasks, scanning procedures including two functional MRI (fMRI) scans as well as structural MRI.
The fMRI will be obtained in non-abstinent participants with breath alcohol concentrations not larger than > 0.3 ‰ and withdrawal severity not more than 4 on the clinical institute withdrawal assessment for alcohol (CIWA-Ar) scale.
Alcohol consumption will be assessed with the Form90 interview. Severity of alcohol dependence will be examined with the Alcohol Dependence Scale (ADS). Drinking situations will be assessed with the Inventory of Drinking Situations (IDS). Trait aspects of craving for alcohol will be measured with the Obsessive Compulsive Drinking Scale (OCDS). To examine state and trait anxiety the State-Trait Anxiety Inventory (STAI) will be used. Depressive symptoms will be measured with the Beck Depression Inventory (BDI) and the State-Trait Depression Scales (STDS). Nicotine consumption will be assessed with the Fagerström Test for Nicotine Dependence.
The following scales will be administered before and after each fMRI scanning: The Alcohol Craving Questionnaire (ACQ), the Alcohol Urge Questionaire (AUQ) and visual analogue scales for craving assessment.
Participants will undergo two fMRI scanning sessions at intervals of one week: one 2 h after administration of nalmefene and one 2 h after administration of placebo, carried out in a randomized order.
MRI examinations include
- a cue-reactivity task;
- an emotional faces task;
- resting-state fMRI;
- structural MRI;
- including preparation, instructions and breaks
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nalmefene Challenge | Experimental | Drug: NalmefeneParticipants will receive 18mg Nalmefene two hours prior to fMRI measurement. During fMRI scanning alcohol cues will be presented. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will receive Placebo two hours prior to fMRI measurement. During fMRI scanning alcohol cues will be presented. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- severe alcohol use disorder according to DSM 5 and "heavy drinking": alcohol consumption >=60g (men) and >=40g (women) (minimum of 5 days / week)
- right-handedness
- normal or corrected to normal vision
- signed written informed consent
Key exclusion criteria (12 listed)
- psychotropic medication within the last 14 days
- severe withdrawal symptoms (CIWA-Ar > 4; Sullivan et al. 1989)
- intoxication (breath alcohol concentration > 0.3 ‰)
- common exclusion criteria for MRI (e.g. metal, claustrophobia)
- positive drug screening (opioids, cannabinoids, benzodiazepines, barbiturates, cocaine, amphetamines)
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 |
|---|---|---|
| NalmefeneAlso: Selincro18mg of Nalmefen will be administered orally | Drug | Nalmefene Challenge |
| PlaceboPlacebo tablet | Drug | Placebo |
Primary outcome
Difference in cue-induced brain activation between two fMRI scans (randomization to an intake of nalmefene (18 mg) or placebo).
Time frame: Primary outcome measures will be assessed on day 2 and day3 after fMRI scan, data collection will take up to 12 months
This difference will be extracted from whole-brain contrast images in the VS and DS using the percentage of activated voxels in these regions of interest (ROI).
Results and safety
The study was stopped early (reason given: Anticipated nr of 25 probands was not reached in terms of full data sets (missing data, low fMRI data quality), but time frame for recruitment ended.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Derived from this study: PubMed 35426492Grundinger N, Gerhardt S, Karl D, Mann K, Kiefer F, Vollstadt-Klein S. The effects of nalmefene on the impulsive and reflective system in alcohol use disorder: A resting-state fMRI study. Psychopharmacology (Berl). 2022 Aug;239(8):2471-2489. doi: 10.1007/s00213-022-06137-1. Epub 2022 Apr 15.
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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.
Sabine Vollstädt-Klein, Prof. Dr. principal investigator
Central Institute of Mental Health, Mannheim
Falk Kiefer, Prof. Dr. principal investigator
Central Institute of Mental Health, Mannheim
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Nalmefene in people with Alcoholism, run by Central Institute of Mental Health, Mannheim at 1 site in Germany.
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 12 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: stopped early, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 stopped early (reason given: Anticipated nr of 25 probands was not reached in terms of full data sets (missing data, low fMRI data quality), but time frame for recruitment ended.). Results are not available in the source record.
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?
Difference in cue-induced brain activation between two fMRI scans (randomization to an intake of nalmefene (18 mg) or placebo). (time frame: Primary outcome measures will be assessed on day 2 and day3 after fMRI scan, data collection will take up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02372318, which also lists 1 linked publication.
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 2 Jul 2017.