Alcohol Use DisorderLeADP5NCT02094196
The Role of Dopaminergic and Glutamatergic Neurotransmission for Dysfunctional Learning in Alcohol Use Disorders
An observational study of Alcohol Use Disorder, run by Technische Universität Dresden at 2 sites in Germany.
Trial summary
The aim of this project is to assess reward- based learning behavior and its association with alterations in dopaminergic and glutamatergic transmission in detoxified alcohol-dependent patients and matched controls. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Alcohol Use Disorder
- What is being tested?
- Alcohol detoxification
- How many people
- 60 participants
- Where
- 2 sitesGermany
- Study dates
- Dec 2012to Dec 2018
- Phase
- Observational
- 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: Detoxified alcohol- dependent patients and age- and gender matched healthy controls living in Germany
Who may be able to join
- Alcohol dependence according to DSM-IV
- Minimum of 72 hours of abstinence, maximum of 21 days of abstinence
- Minimum of three years of alcohol dependence
- Low severity of withdrawal symptoms
- Ability to provide fully informed consent and to use self- rating scales
Who cannot join
- Lifetime history of DSM- IV bipolar or psychotic disorder
- Current threshold DSM-IV diagnosis of any following disorders: current major - depressive disorder, generalized anxiety disorder, PTSD, borderline personality disorder or obsessive- compulsive disorder
- History of substance dependence other than alcohol or nicotine dependence
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
Charité Berlin, Division of Neuroimaging
Berlin, 10115
Charité - Universitätsmedizin Berlin
Berlin, 10117
About this study
Official title: The Role of Dopaminergic and Glutamatergic Neurotransmission for Dysfunctional Learning in Alcohol Use Disorders (LeAD P5)
The aim of this project is to assess reward- based learning behavior and its association with alterations in dopaminergic and glutamatergic transmission in detoxified alcohol-dependent patients and matched controls.
The investigators will explore how these alterations interact with clinical and psychosocial factors which can modify the relapse risk and learning deficits.
Read more
Patients will be detoxified in an inpatient setting. Clinical assessments, behavioral paradigms of learning and brain imaging will be carried out within at least 4 half- lives after any psychotropic medication.
The investigators will implement and apply functional imaging paradigms assessing Pavlovian-to-instrumental transfer and reversal learning tasks and associate model parameters of learning with alcohol craving, intake and prospective relapse risk.
In this project, the impact of the dopamine x glutamate interaction on learning deficits and consecutive relapse probability is targeted with [18F]fallypride PET and the measurement of absolute concentrations of glutamate with magnetic resonance spectroscopy (MRS).
Read the detailed description
Alcohol consumption despite negative consequences may rely on impaired flexibility in adapting the behavior to environmental changes, i.e. learning in response to reward contingencies. This learning deficit is of clinical relevance particularly during therapy and for the psychosocial outcome.
The reduced availability of central dopamine D2-receptors in detoxified alcohol dependent patients observed in PET investigations and their hypothetical effects on reward-related learning are in line with evidence for learning deficits in hypodopaminergic states, particularly for avoidance learning in non-dependent samples. Growing evidence indicates that the learning-related striatal dopamine signals are modulated by higher executive functions involving, e.g., the prefrontal cortex.
Here, broad glutamatergic outputs of the prefrontal cortex are crucial for subcortical learning mechanisms and match with recent models of interactive dopamine-glutamate dysfunctions and models of neurotrophic signaling in alcohol dependence.
- Conditions
- Alcohol Use Disorder
- Being tested
- Alcohol detoxification
- Keywords
- Reward- based learning, Pavlovian-to-instrumental transfer, Relapse Risk, Positron emission tomography (PET), Magnetic resonance spectroscopy (MRS), Dopamine receptor availability, Glutamate
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alcohol detoxificationOther
Also called Alcohol- dependent patients
Detoxified alcohol- dependent patients in an inpatient setting
| Study group | Role | What they receive |
|---|---|---|
| Controls, highrisk for AD | Community-based ad-hoc participants, high risk for alcohol dependence, matched to inpatients by sociodemographics | |
| Controls, low risk for AD | Community-based ad-hoc participants, low risk for alcohol dependence, matched to inpatients by sociodemographics | |
| Alcohol detoxification | Inpatients with alcohol dependence from local psychiatric hospital wards (18-65 years old) Receives: Other: Alcohol detoxification |
What is being measured
The primary outcome is the main question the study is designed to answer.
Striatal D2-receptor availability (PET) and prefrontal glutamate concentration (MRS)
reduction in striatal D2-receptor availability and a increase in prefrontal glutamate concentration in alcohol-dependent patients compared to healthy controls
Measured: first assessment time point (alc. dependent pat. up to 21 days after detoxification)
Secondary outcomes (2)
behavioral data in reward-habit-learning paradigms
Reduced learning speed and PIT withdrawal score in the probabilistic reversal learning task
Measured: first assessment time point (alc. dependent pat. up to 21 days after detoxification)
Treatment response
test the predictive effects of striatal D2-receptor availability and prefrontal glutamate availability for treatment outcome (relapse vs abstinence) in alcohol-dependent patients
Measured: 12-month follow-up period beginning after first assessment timepoint
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2014 (estimated)
- Study startDec 2012
- Primary completionApr 2018
- Study completionDec 2018
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 Alcohol Use DisorderStudies of the same condition, open and under way.
- More trials run by Technische Universität DresdenThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Technische Universität Dresden
- Sponsor type
- University, hospital or other
- Collaborators
- Charite University, Berlin, Germany
- Responsible party
- Sponsor
- Investigators
- Jürgen Gallinat, Prof MD, Principal investigator, Charite University, Berlin, GermanyAndreas Heinz, Prof MD, Study chair, Charite University, Berlin, GermanyHans-Ulrich Wittchen, Prof PhD, Study director, Technische Universität Dresden, Dresden, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02094196
- Sponsor's protocol ID
- GA707/6-1
- Acronym
- LeADP5
- Status last verified
- Jul 2020
- First submitted
- 20 Mar 2014
- Last updated
- 30 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Spitta G, Gleich T, Maricic LM, Rosenthal A, Schubert F, Aydin S, Heinz A, Gallinat J. Reduced GABA Levels in the ACC of Actively Drinking High Risk Individuals Compared to Recently Detoxified Alcohol-Dependent Patients. J Integr Neurosci. 2024 Oct 14;23(10):190. doi: 10.31083/j.jin2310190.
PubMed 39473159
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Dopaminergic and Glutamatergic Neurotransmission for Dysfunctional Learning in Alcohol Use Disorders (LeAD P5)
- ClinicalTrials.gov ID
- NCT02094196
- Acronym / sponsor ID
- LeADP5 / GA707/6-1
- Conditions
- Alcohol Use Disorder
- Keywords
- Reward- based learning, Pavlovian-to-instrumental transfer, Relapse Risk, Positron emission tomography (PET), Magnetic resonance spectroscopy (MRS), Dopamine receptor availability, Glutamate
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Technische Universität DresdenUniversity, hospital or other
- Collaborators
- Charite University, Berlin, Germany
- Study start
- Dec 2012 (actual)
- Primary completion
- Apr 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 21 Mar 2014 (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 project is to assess reward- based learning behavior and its association with alterations in dopaminergic and glutamatergic transmission in detoxified alcohol-dependent patients and matched controls.
The investigators will explore how these alterations interact with clinical and psychosocial factors which can modify the relapse risk and learning deficits.
Patients will be detoxified in an inpatient setting. Clinical assessments, behavioral paradigms of learning and brain imaging will be carried out within at least 4 half- lives after any psychotropic medication.
The investigators will implement and apply functional imaging paradigms assessing Pavlovian-to-instrumental transfer and reversal learning tasks and associate model parameters of learning with alcohol craving, intake and prospective relapse risk.
In this project, the impact of the dopamine x glutamate interaction on learning deficits and consecutive relapse probability is targeted with [18F]fallypride PET and the measurement of absolute concentrations of glutamate with magnetic resonance spectroscopy (MRS).
Detailed description
Alcohol consumption despite negative consequences may rely on impaired flexibility in adapting the behavior to environmental changes, i.e. learning in response to reward contingencies. This learning deficit is of clinical relevance particularly during therapy and for the psychosocial outcome.
The reduced availability of central dopamine D2-receptors in detoxified alcohol dependent patients observed in PET investigations and their hypothetical effects on reward-related learning are in line with evidence for learning deficits in hypodopaminergic states, particularly for avoidance learning in non-dependent samples. Growing evidence indicates that the learning-related striatal dopamine signals are modulated by higher executive functions involving, e.g., the prefrontal cortex.
Here, broad glutamatergic outputs of the prefrontal cortex are crucial for subcortical learning mechanisms and match with recent models of interactive dopamine-glutamate dysfunctions and models of neurotrophic signaling in alcohol dependence.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Controls, highrisk for AD | – | –Community-based ad-hoc participants, high risk for alcohol dependence, matched to inpatients by sociodemographics |
| Controls, low risk for AD | – | –Community-based ad-hoc participants, low risk for alcohol dependence, matched to inpatients by sociodemographics |
| Alcohol detoxification | – | Other: Alcohol detoxificationInpatients with alcohol dependence from local psychiatric hospital wards (18-65 years old) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Detoxified alcohol- dependent patients and age- and gender matched healthy controls living in Germany
Key inclusion criteria (5 listed)
- Alcohol dependence according to DSM-IV
- Minimum of 72 hours of abstinence, maximum of 21 days of abstinence
- Minimum of three years of alcohol dependence
- Low severity of withdrawal symptoms
- Ability to provide fully informed consent and to use self- rating scales
Key exclusion criteria (3 listed)
- Lifetime history of DSM- IV bipolar or psychotic disorder
- Current threshold DSM-IV diagnosis of any following disorders: current major - depressive disorder, generalized anxiety disorder, PTSD, borderline personality disorder or obsessive- compulsive disorder
- History of substance dependence other than alcohol or 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 |
|---|---|---|
| Alcohol detoxificationAlso: Alcohol- dependent patientsDetoxified alcohol- dependent patients in an inpatient setting | Other | Alcohol detoxification |
Primary outcome
Striatal D2-receptor availability (PET) and prefrontal glutamate concentration (MRS)
Time frame: first assessment time point (alc. dependent pat. up to 21 days after detoxification)
reduction in striatal D2-receptor availability and a increase in prefrontal glutamate concentration in alcohol-dependent patients compared to healthy controls
2 secondary outcomes
behavioral data in reward-habit-learning paradigms
Time frame: first assessment time point (alc. dependent pat. up to 21 days after detoxification)
Treatment response
Time frame: 12-month follow-up period beginning after first assessment timepoint
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2020.
- Derived from this study: PubMed 39473159Spitta G, Gleich T, Maricic LM, Rosenthal A, Schubert F, Aydin S, Heinz A, Gallinat J. Reduced GABA Levels in the ACC of Actively Drinking High Risk Individuals Compared to Recently Detoxified Alcohol-Dependent Patients. J Integr Neurosci. 2024 Oct 14;23(10):190. doi: 10.31083/j.jin2310190.
- English study descriptionLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Jürgen Gallinat, Prof MD principal investigator
Charite University, Berlin, Germany
Andreas Heinz, Prof MD study chair
Charite University, Berlin, Germany
Hans-Ulrich Wittchen, Prof PhD study director
Technische Universität Dresden, Dresden, Germany
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alcohol Use Disorder, run by Technische Universität Dresden at 2 sites 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 5 inclusion and 3 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: finished, as of the sponsor's last update on 30 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Striatal D2-receptor availability (PET) and prefrontal glutamate concentration (MRS) (time frame: first assessment time point (alc. dependent pat. up to 21 days after detoxification)). 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 NCT02094196, 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 30 Jul 2020.