search
Back to results

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

Primary Purpose

Alcohol Addiction

Status
Terminated
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Placebo
Naltrexone
Sponsored by
RWTH Aachen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcohol Addiction

Eligibility Criteria

21 Years - 45 Years (Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

  • University Hospital RWTH Aachen

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Other

Other

Arm Label

First Arm

Second Arm

Third Arm

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Pharmacological effect of ethanol on dopamine D2 receptor availability in healthy men measured with [18F]-fallypride Positron Emission Tomography.
Pharmacological effect of ethanol on the dopamine synthesis rate of the ventral and dorsal striatum in healthy men measured with [18F]-fluoro-DOPA PET.
Pharmacological effect of Naltrexone on dopamine D2 receptor availability in healthy men measured with [18F]-fallypride Positron Emission Tomography.
Pharmacological effect of Naltrexone on the dopamine synthesis rate of ventral and dorsal striatum in healthy men measured with [18F]-fluoro-DOPA PET.

Full Information

First Posted
February 18, 2019
Last Updated
September 10, 2019
Sponsor
RWTH Aachen University
search

1. Study Identification

Unique Protocol Identification Number
NCT03854942
Brief Title
Study of the Opioid Modulation of the Effect of Alcohol on the Dopaminergic Reward System
Official Title
Opioid Modulation of the Effect of Alcohol on the Dopaminergic Reward System: a [18F]-Fallypride- and [18F]-Fluoro-DOPA-PET Study.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Terminated
Why Stopped
Recruitment rate could not be met in the study period, review group was dissolved before regular end of study. Recruitment was therefore terminated.
Study Start Date
August 30, 2011 (Actual)
Primary Completion Date
December 13, 2017 (Actual)
Study Completion Date
December 13, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
RWTH Aachen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Addiction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
Participant
Allocation
Randomized
Enrollment
43 (Actual)

8. Arms, Groups, and Interventions

Arm Title
First Arm
Arm Type
Other
Arm Description
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
Arm Title
Second Arm
Arm Type
Other
Arm Description
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
Arm Title
Third Arm
Arm Type
Other
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo oral tablet daily
Intervention Type
Drug
Intervention Name(s)
Naltrexone
Intervention Description
Naltrexone (Nemexin) oral tablet 50 mg daily for 2 days, Naltrexone (Nemexin) oral tablet 100 mg daily for 5 days
Primary Outcome Measure Information:
Title
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
Title
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
Secondary Outcome Measure Information:
Title
Pharmacological effect of ethanol on dopamine D2 receptor availability in healthy men measured with [18F]-fallypride Positron Emission Tomography.
Time Frame
28 days
Title
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
Title
Pharmacological effect of Naltrexone on dopamine D2 receptor availability in healthy men measured with [18F]-fallypride Positron Emission Tomography.
Time Frame
28 days
Title
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
Other Pre-specified Outcome Measures:
Title
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
Title
Relationship between impulsive behaviour and functionality of the dopamine synthesis rate and dopamine D2 receptor availability
Description
Evaluation of impulsive behaviour using BIS (Barratt Impulsiveness Scale) questionnaire
Time Frame
28 days
Title
Relationship between impulsive behaviour and functionality of the dopamine synthesis rate and dopamine D2 receptor availability
Description
Evaluation of impulsive behaviour using Neo-FFI (NEO-Fünf-Faktoren-Inventar) questionnaire
Time Frame
28 days
Title
Relationship between impulsive behaviour and functionality of the dopamine synthesis rate and dopamine D2 receptor availability
Description
Evaluation of impulsive behaviour using I7 (Impulsivitätsfragebogen (impulsivity questionnaire) nach Eysenck) questionnaire
Time Frame
28 days
Title
Interaction between subjective alcohol effects and placebo/naltrexone effects
Description
Exploratively, the interaction between subjective alcohol effects and placebo/naltrexone effects will be investigated using VAS (visual analogue scale of alcoholic desire) questionnaire.
Time Frame
28 days
Title
Interaction between subjective alcohol effects and placebo/naltrexone effects
Description
Exploratively, the interaction between subjective alcohol effects and placebo/naltrexone effects will be investigated using OCDS (Obsessive Compulsive Drinking Scale) questionnaire.
Time Frame
28 days
Title
Interaction between subjective alcohol effects and placebo/naltrexone effects
Description
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.
Time Frame
28 days

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Facility Information:
Facility Name
University Hospital RWTH Aachen
City
Aachen
ZIP/Postal Code
52074
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs