Reward-specific Changes of the Chemical Messenger Dopamine in the Brain of Healthy and Depressed People

November 4, 2024 updated by: Rupert Lanzenberger, Medical University of Vienna

Reward-specific Changes of Cerebral Dopamine Synthesis in Healthy Volunteers and Depressed Patients

Major depressive disorder was shown to be associated with pathological alterations within neurotransmitter systems of the brain. Based on earlier study results, it is assumed that the neurotransmitter dopamine is relevant for several symptoms of depression, e.g., loss of interest or pleasure and lack of motivation. Thus, it is assumed that the synthesis of dopamine in the brain of depressed individuals could be impaired. The specific effect of common antidepressants on the human reward system in depression has not yet been sufficiently investigated. In particular, it is unclear whether depressed patients exhibit reward-specific changes of dopamine synthesis, and whether or not these changes can be differentially affected by diverse types of antidepressants. Neurotransmitter systems can be visualized in the brain using positron emission tomography (PET). Additionally, brain structure and function can be studied using magnetic resonance imaging (MRI). For the visualization of dopamine synthesis in the brain, the radioligand [18F]FDOPA can be used in PET measurements. To assess task-relevant changes of diverse radioligands and thus specific metabolic processes in the brain during specific tasks, a recently developed PET-approach can be used which has already been successfully applied in a pilot study with healthy volunteers. In the present project, 60 depressed subjects and 30 healthy controls will undergo PET/MR-imaging twice. Depressed subjects will be assigned to 1 of 2 treatment groups. 30 depressive subjects will receive bupropion, the other 30 patients will be treated with escitalopram. After a treatment period of 6 weeks, the 2nd PET measurement will be performed in all participants, aiming to detect potential reward-specific changes of dopamine synthesis. The investigators hypothesize that reward-specific changes of dopamine synthesis will be lower in depressed subjects than in healthy controls, that reward-specific changes of dopamine synthesis will be significantly higher in the bupropion group than in the escitalopram group, and that the changes of dopamine synthesis will be associated with functional changes in the brain (measured by simultaneous functional MRI scans). This will be the first study comparing the effects of escitalopram and bupropion on task-specific dopamine synthesis and thus on the human reward system. The study is expected to yield new insights for individual treatment concepts in the therapy of depression.

Study Overview

Status

Status

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

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 (Estimated)

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.
120

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 4

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Austria
      • Vienna, Austria, 1090
        • Recruiting
        • Medical University of Vienna
        • Contact:
        • Contact:
          • Godber Mathis Godbersen, Dr.med.univ, PhD
        • Contact:
          • Patricia Anna Handschuh, Dr.med.univ, BA

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Male and female subjects aged between 18-65 years of age
  • Depressive patients: DSM-IV diagnosis of MDD following SCID I, HDRS29, MADRS and BDI-II
  • Satisfactory general health as determined by past medical history, physical examination, vital signs at screening
  • Vital signs measured after 3 minutes resting in the supine position must be within the following ranges: oral body temperature between 35.0-37.5 °C, systolic blood pressure 90-140 mmHg, diastolic blood pressure 50-90 mm Hg, pulse rate 40-100 bpm
  • Subjects must weigh 50-100 kg to participate in this study with a BMI within 19-26.
  • Sufficient visual and auditory performance for neuropsychological testing
  • Written informed consent will be obtained prior to the start of any study procedures. Therefore, willingness and competence to sign the informed consent form is needed.
  • Potential patients must be able to communicate well with the investigator and comply with the requirements of the study
  • Only participants who are legally authorized to give informed consent will be included in the present study.

Exclusion Criteria:

  • Depressed patients: Presence of any severe / unstable neurological, somatic or psychiatric comorbidity
  • Healthy controls: Any psychiatric disease or any severe / unstable neurological or somatic disease
  • Presence of psychotic symptoms
  • Acute suicidality
  • Any contraindication for magnetic resonance or PET imaging
  • Presence of any metallic implant in the head
  • History of clinically significant drug allergy; history of atopic allergy (asthma, urticaria, eczematous dermatitis). A known hypersensitivity to one of the study drugs or multiple study drugs (known hypersensitivity to bupropion, escitalopram)
  • Other clinically significant abnormality on physical, neurological, or laboratory examination or on electrocardiogram (ECG) that, in the opinion of the investigator precludes the patient from the study
  • Ingestion of antidepressants or other psychotropic agents within the last 6 months Previous escitalopram- or bupropion intake
  • Antidepressive trials wit DBS, electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) or Ketamine
  • Current smoking, substance abuse including alcohol, drugs of abuse, or any medication in a manner which is indicative of substance-related disorders (e.g. substance dependency) according to DSM-IV
  • Failure to comply with the study protocol or follow the instructions of the investigators
  • Positive urine pregnancy test
  • Known pregnancy or lactation
  • MRI scan that shows evidence of stroke, infarct, or other space occupying lesion or structural abnormality
  • History of any other drug or alcohol abuse or misuse
  • Participation in any clinical investigation within 12 weeks prior to dosing
  • Evidence from an Allen test of incomplete communication between the radial and ulnar artery, in either hand
  • Significant radiation exposure (>5 mSv) in the frame of participation in trials within the past 10 years

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: Parallel Assignment
  • Masking: Triple

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.
Active Comparator: Antidepressant treatment in MDD patients with bupropion
Bupropion 150 mg daily after baseline PET/MRI or MRI/MRS over 6-8 weeks
Drug: WELLBUTRIN SR (Bupropion HCI) Sustained-Release Tablets, 150 mg; GlaxoSmithKline
Bupropion 150 mg daily after baseline PET/MRI or MRI/MRS over 6-8 weeks
Active Comparator: Antidepressant treatment in MDD patients with escitalopram
Escitalopram 10 mg daily after baseline PET/MRI or MRI/MRS over 6-8 weeks
Drug: Cipralex (escitalopram)
Escitalopram 10 mg daily after baseline PET/MRI or MRI/MRS over 6-8 weeks
No Intervention: Healthy Controls without antidepressant intake
Healthy controls will only attend imaging procedures without medication intake

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
Measure Description
Time Frame
Changes of the reward specific dopamine synthesis rate in the nucleus accumbens of depressed individuals after 6-8 weeks of antidepressant intake assessed via functional PET
Time Frame: 6-8 weeks
Reward-specific dopamine synthesis rate: Assessment of the net influx constant Ki in the nucleus accumbens via functional PET using [18F]FDOPA as an index of the dopamine synthesis rate
6-8 weeks
Relationship between potential changes of the reward-specific dopamine synthesis rate in the nucleus accumbens assessed via functional PET and treatment response in depressed individuals after 6-8 weeks of antidepressant intake
Time Frame: 6-8 weeks
Reward-specific dopamine synthesis rate: Assessment of the net influx constant Ki in the nucleus accumbens via functional PET using [18F]FDOPA as an index of the dopamine synthesis rate; Treatment response rates will be assessed at baseline and after 6-8 weeks of antidepressant therapy via the Hamilton Depression Rating Scale with 29 items (HDRS29) and the Montgomery-Åsberg Depression Rating Scale (MADRS).
6-8 weeks
Difference in changes to the reward-specific dopamine synthesis rate in the nucleus accumbens assessed via functional PET in depressed patients taking bupropion vs. escitalopram after 6-8 weeks of therapy
Time Frame: 6-8 weeks
Reward-specific dopamine synthesis rate: Assessment of the net influx constant Ki in the nucleus accumbens via functional PET using [18F]FDOPA as an index of the dopamine synthesis rate
6-8 weeks

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
Measure Description
Time Frame
Relationship between the reward-specific dopamine synthesis rate (assessed via functional PET) and fMRI activation across healthy volunteers and depressed patients, both at baseline and after 6-8 weeks of therapy
Time Frame: 6-8 weeks
Reward-specific dopamine synthesis rate: Assessment of the net influx constant Ki in the nucleus accumbens via functional PET using [18F]FDOPA as an index of the dopamine synthesis rate; fMRI activation: Blood-Oxygenation-Level Dependent Signal via functional Magnetic Resonance Imaging
6-8 weeks
Remission rates in depressed patients being treated with either escitalopram or bupropion in a longitudinal design
Time Frame: 6-8 weeks
Remission rates will be assessed at baseline and after 6-8 weeks of antidepressant therapy via the Hamilton Depression Rating Scale with 29 items (HDRS29) and the Montgomery-Åsberg Depression Rating Scale (MADRS).
6-8 weeks
Test-retest reliability for the quantification of dopamine synthesis rates in healthy volunteers via functional PET
Time Frame: 6-8 weeks
Reward-specific dopamine synthesis rate: Assessment of the net influx constant Ki in the nucleus accumbens via functional PET using [18F]FDOPA as an index of the dopamine synthesis rate; assessed at baseline and after 6-8 weeks without any interventions in between
6-8 weeks

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
Changes in cerebral GABA and Glutamate after antidepressant treatment measured by Magnetic Resonance Spectroscopy (MRS)
Time Frame: 6-8 weeks
GABA+/tCr, GABA+/Glx, and Glx/tCr ratios will be assessed via MRS before and after antidepressant treatment over 6-8 weeks. This will be an optional measurement.
6-8 weeks

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.
Medical University of Vienna

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Austrian Science Fund (FWF)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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.
December 1, 2022

Primary Completion (Estimated)

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 1, 2026

Study Completion (Estimated)

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 1, 2026

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).
October 31, 2024

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.
November 4, 2024

First Posted (Estimated)

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.
November 5, 2024

Study Record Updates

Last Update Posted (Estimated)

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.
November 5, 2024

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.
November 4, 2024

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.
November 1, 2024

More Information

Terms related to this study

Keywords

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.
  • 2321/2019
  • 2019-004880-33 (EudraCT Number)

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

product manufactured in and exported from the U.S.

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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