Reward-specific changes of cerebral dopamine synthesis in healthy volunteers and depressed patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Vienna

Participant type

Patients, Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

5 Jan 2023 → ongoing

Decision date (initial)

2025-01-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Medical University of Vienna, University Department of Psychiatry and Psychotherapy · FWF

External identifiers

EU CT number

2024-518226-32-00

EudraCT number

2019-004880-33

ClinicalTrials.gov

NCT06675851

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Dose response, Therapy, Diagnosis, Pharmacokinetic

- Identifying reward-specific alterations in dopamine synthesis (PET) in the nucleus accumbens (NAcc) in patients with Major Depressive Disorder (MDD) compared to healthy volunteers applying the Monetary Incentive Delay Task
- To assess the effect of bupropion on reward consumption and reward-specific NAcc dopamine synthesis rates in patients with MDD in a longitudinal design
- To assess the relationship between reward-specific NAcc dopamine synthesis and treatment response in MDD

Secondary objectives 10

1. To analyze the relationship between reward-specific dopamine synthesis rates and fMRI activation across healthy volunteers and patients with MDD applying the Monetary Incentive Delay Task in both imaging modalities
2. To identify HDRS29, MADRS and BDI-II remission rates in patients with MDD while and after being treated with bupropion in a longitudinal design
3. To assess the test-retest reliability of quantifying dopamine synthesis rates induced by experimental tasks applying the same PET protocol across healthy controls in a longitudinal design
4. Magnetic Resonance Spectroscopy and Imaging (optional): - To investigate the potential relationship between reward-specific nucleus accumbens dopamine synthesis and GABA-/glutamatergic neurotransmission
5. Magnetic Resonance Spectroscopy and Imaging (optional): -To reveal baseline differences in GABA-/glutamatergic neurotransmission between depressed and healthy subjects
6. Magnetic Resonance Spectroscopy and Imaging (optional): - To identify the potential relationship between clinical outcome after antidepressant therapy with bupropion and changes in GABA/glutamate in the brain
7. Microbiome Analysis (optional): - To investigate the potential relationship between gut microbiome composition and reward-specific NAcc DA synthesis across patients with MDD in an exploratory design
8. Microbiome Analysis (optional): - To assess whether bupropion alters gut microbial composition longitudinally
9. Microbiome Analysis (optional): - To explore the predicitive value of baseline gut microbiome composition for antidepressant treatment efficacy with bupropion
10. Microbiome Analysis (optional): - To explore associations between longitudinal changes in gut microbiome composition and clinical treatment response after bupropion treatment

Conditions and MedDRA coding

Major Depression

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Male and female subjects aged between 18-65 years of age
2. Depressive patients: DSM-IV or ICD-10 diagnosis of MDD, Depressive Episode, or Recurrent Depressive Disorder following SCID I, HDRS29, MADRS and BDI-II
3. Satisfactory general health as determined by past medical history, physical examination, vital signs at screening
4. 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
5. Subjects must weigh 50-100 kg to participate in this study with a BMI (body mass index) within 19-26. Exceptions might be made based on clinical impression (e.g., elevated BMI due to above-average muscle mass).
6. Sufficient visual and auditory performance for neuropsychological testing
7. 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.
8. Potential patients must be able to communicate well with the investigator and comply with the requirements of the study
9. Only participants who are legally authorized to give informed consent will be included in the present study.
10. Healthy subjects: HDRS29 ≤ 8, MADRS ≤ 6 and BDI-II < 13

Exclusion criteria 20

1. Depressed patients: Presence of any severe / unstable neurological, somatic or psychiatric comorbidity
2. Healthy controls: Any unstable / severe psychiatric disease or any severe / unstable neurological or somatic disease
3. Presence of psychotic symptoms
4. Acute suicidality
5. Any contraindication for magnetic resonance or PET imaging
6. Presence of any metallic implant in the head
7. History of clinically significant drug allergy; history of severe atopic allergy (asthma, urticaria, eczematous dermatitis). A known hypersensitivity to one of the study drugs or multiple study drugs (known hypersensitivity to bupropion, mirtazapine, carbidopa or entacapone)
8. 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
9. Depressed patients: Therapy with dopaminergic antidepressants including bupropion or other dopaminergic psychotropic agents (antipsychotics, stimulants, etc.) within the last 3 months
10. Healthy controls: Therapy with any kind of psychotropic medication within the last 3 months
11. Antidepressive trials with deep brain stimulation (DBS), electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) or Ketamine
12. Current regular smoking, regular 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
13. Failure to comply with the study protocol or follow the instructions of the investigators
14. Positive urine pregnancy test
15. Known pregnancy or lactation
16. MRI scan that shows evidence of stroke, infarct, or other space-occupying lesion or structural abnormality
17. History of any other drug or alcohol abuse or misuse
18. Participation in any clinical investigation within 12 weeks prior to dosing. Exceptions can be made, provided that the study was conducted under the supervision of Univ.-Prof. PD Dr. med. Rupert Lanzenberger and his study team, and that the preceding study did not involve any radiation exposure
19. Evidence from an Allen test of incomplete communication between the radial and ulnar artery, in either hand
20. Significant radiation exposure (>5 mSv) in the frame of participation in trials within the past 10 years

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Reward-specific changes of dopamin-synthesis

Secondary endpoints 3

1. To analyze the relationship between reward-specific dopamine synthesis and fMRI activation across healthy volunteers and patients with MDD
2. To identify remission rates in MDD patients being treated with either escitalopram OR bupropion in a longitudinal design
3. Test-retest reliability for the quantification of dopamine synthesis rates in healthy volunteers

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Vienna

Sponsor organisation

Medical University Of Vienna

Address

Spitalgasse 23, Alsergrund Alsergrund

City

Vienna

Postcode

1090

Country

Austria

Scientific contact point

Organisation

Medical University Of Vienna

Contact name

Department of Psychiatry and Psychotherapy, Division of General Psychiatry

Public contact point

Organisation

Medical University Of Vienna

Contact name

Department of Psychiatry and Psychotherapy, Division of General Psychiatry

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications