Study of the Opioid Modulation of the Effect of Alcohol on the Dopaminergic Reward System

September 10, 2019 updated by: RWTH Aachen University

Opioid Modulation of the Effect of Alcohol on the Dopaminergic Reward System: a [18F]-Fallypride- and [18F]-Fluoro-DOPA-PET Study.

About 10% of the calculable loss of health and quality of life in industrial countries can be attributed to excessive alcohol consumption. Behavioural pharmacological, genetic and clinical studies on alcohol dependence suggest a multifactorial model for the development of the disease, which ascribes an important role in the development of the disease to genetic variance, educational style and continued substance use. Animal and human experimental studies suggest that continued alcohol consumption leads to a pathological activation of the mesolimbic reward system. In the presented study, the modification of the alcohol-mediated activation of the mesolimbic reward system by the administration of the opiate antagonist naltrexone will be investigated in a human in vivo model. The aim is to gain important insights for the further development of pharmacological treatment options for alcohol dependence. Further development of pharmacological treatment options for alcohol dependence seems urgently necessary in order to slow down the high tendency to relapse and prolong the short abstinence period.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
43

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Aachen, Germany, 52074
        • University Hospital RWTH Aachen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 45 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • age: 21-45 years
  • The subject is able to understand the nature, extent and individual consequences of the clinical trial
  • Maintained ability to give consent, certified by a psychiatrist (specialist)
  • A personally dated informed consent form signed by the test participant
  • No current and/or historical psychiatric disorder (secured by standardized psychiatric interview (DIAX: Composite International Diagnostic Interview))
  • Non-smokers (no nicotine addiction within the last 6 months prior to sequential allocation)
  • OPRM1 Asp40 carrier (functional polymorphism in amino acid residue 40 of μ-opioid receptor gene (OPRM1)) (in AC for inclusion in first and third treatment arm)
  • Highly effective contraception method with a failure rate of <1%: Hormonal contraceptive methods (oral: "contraceptive pill", incl. combined oral contraceptives; subcutaneous implants; injectable contraceptives); intrauterine pessary, vasectomy of the partner, tube ligation ("sterilisation") or sexual abstinence
  • Persons who are legally competent and mentally able to understand and follow the instructions of the study staff
  • MRI capability

Exclusion Criteria:

  • hypersensitivity to the investigational product or a chemically similar substance or component of the investigational product
  • Participation in other clinical trials during or within 6 months prior to this clinical trial
  • Medical or psychological circumstances which may jeopardise the proper conduct of the clinical trial
  • Physical illnesses which could interfere with the planned examinations according to their type and severity, could have an influence on the parameters to be examined or could endanger the volunteer during the course of the examination
  • Inability to adhere to the study protocol
  • Limited or completely revoked legal capacity
  • Acute suicidal tendency or external hazard
  • Poor overall condition
  • Participation in a study using ionising radiation in the last five years.
  • Regular medication (e.g. MAO inhibitors)
  • Alcohol abuse, alcohol dependency or addiction illness / abuse of addictive substances in history
  • Existence of other exclusion criteria for participation in MRI examinations (non-removable metal parts in the body, left-handedness, pacemakers)
  • Known hypersensitivity to carbidopa or any of the other components
  • Relevant organic diseases: in particular: Narrow angle glaucoma, vascular diseases, central nervous neurological diseases; body weight of more than 150 kg (contraindications PET - scan)
  • Clinically significant deviations in clinical chemistry or haematology or clinically significant abnormalities
  • Melanoma-specific skin lesions or anamnesis of a previous melanoma disease
  • Persons who are accommodated in an establishment by court order or official order
  • Persons who are dependent on or have an employment relationship with the sponsor or investigator

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: SEQUENTIAL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
OTHER: First Arm
7 days placebo intake - i.v. injection of physiological saline solution (0,9%) - PET followed by 7 days placebo intake - i.v. injection of ethanol solution (6 Vol.-%) - PET
Drug: Placebo
Placebo oral tablet daily
OTHER: Second Arm
7 days placebo intake - i.v. injection of physiological saline solution (0,9%) - PET - 7 days naltrexone intake (Nemexin, 50 mg once daily during the first 2 days, 100 mg daily for the following 5 days) - injection of physiological saline solution (0,9%) - PET
Drug: Placebo
Placebo oral tablet daily
Drug: Naltrexone
Naltrexone (Nemexin) oral tablet 50 mg daily for 2 days, Naltrexone (Nemexin) oral tablet 100 mg daily for 5 days
OTHER: Third Arm
7 days placebo intake - i.v. injection of ethanol solution (6 Vol.-%) - PET - 7 days naltrexone (Nemexin, 50 mg once daily during the first 2 days, 100 mg daily for the following 5 days) intake - i.v. injection of ethanol solution (6 Vol.-%) - PET
Drug: Placebo
Placebo oral tablet daily
Drug: Naltrexone
Naltrexone (Nemexin) oral tablet 50 mg daily for 2 days, Naltrexone (Nemexin) oral tablet 100 mg daily for 5 days

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Pharmacological effect of naltrexone on the dopamine synthesis rate of a healthy OPRM1 Asp40-bearing men under the influence of alcohol measured with [18F]-fluoro-DOPA PET.
Time Frame: 28 days
28 days
Dopamine D2 receptor availability in the structures of the ventral and dorsal striatum of a healthy µ-opioid receptor gen (OPRM1, Asp40 Allel)-bearing men under the influence of alcohol measured with [18F]-fallypride Positron Emission Tomography.
Time Frame: 28 days
28 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Pharmacological effect of ethanol on dopamine D2 receptor availability in healthy men measured with [18F]-fallypride Positron Emission Tomography.
Time Frame: 28 days
28 days
Pharmacological effect of ethanol on the dopamine synthesis rate of the ventral and dorsal striatum in healthy men measured with [18F]-fluoro-DOPA PET.
Time Frame: 28 days
28 days
Pharmacological effect of Naltrexone on dopamine D2 receptor availability in healthy men measured with [18F]-fallypride Positron Emission Tomography.
Time Frame: 28 days
28 days
Pharmacological effect of Naltrexone on the dopamine synthesis rate of ventral and dorsal striatum in healthy men measured with [18F]-fluoro-DOPA PET.
Time Frame: 28 days
28 days

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Modulation of extrastriatal dopamine D2/D3 receptor availability measured with [18F]-fallypride in structures of the anterior cingulum using Positron Emission Tomography.
Time Frame: 28 days
28 days
Relationship between impulsive behaviour and functionality of the dopamine synthesis rate and dopamine D2 receptor availability
Time Frame: 28 days
Evaluation of impulsive behaviour using BIS (Barratt Impulsiveness Scale) questionnaire
28 days
Relationship between impulsive behaviour and functionality of the dopamine synthesis rate and dopamine D2 receptor availability
Time Frame: 28 days
Evaluation of impulsive behaviour using Neo-FFI (NEO-Fünf-Faktoren-Inventar) questionnaire
28 days
Relationship between impulsive behaviour and functionality of the dopamine synthesis rate and dopamine D2 receptor availability
Time Frame: 28 days
Evaluation of impulsive behaviour using I7 (Impulsivitätsfragebogen (impulsivity questionnaire) nach Eysenck) questionnaire
28 days
Interaction between subjective alcohol effects and placebo/naltrexone effects
Time Frame: 28 days
Exploratively, the interaction between subjective alcohol effects and placebo/naltrexone effects will be investigated using VAS (visual analogue scale of alcoholic desire) questionnaire.
28 days
Interaction between subjective alcohol effects and placebo/naltrexone effects
Time Frame: 28 days
Exploratively, the interaction between subjective alcohol effects and placebo/naltrexone effects will be investigated using OCDS (Obsessive Compulsive Drinking Scale) questionnaire.
28 days
Interaction between subjective alcohol effects and placebo/naltrexone effects
Time Frame: 28 days
Exploratively, the interaction between subjective alcohol effects and placebo/naltrexone effects will be investigated using ESA (Erfassung subjektiver Alkoholwirkungen (Determination of subjective alcohol effects)) questionnaire.
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
RWTH Aachen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 30, 2011

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 13, 2017

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 13, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 18, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 25, 2019

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 26, 2019

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 12, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 10, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 10-002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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