BUPROPION HYDROCHLORIDE for Major Depressive Disorder

Inclusion criteria

• {"criterion_text":"- Male and female subjects aged between 18-65 years of age\n- Healthy subjects: HDRS29 ≤ 8, MADRS ≤ 6 and BDI-II < 13\n- Depressive patients: DSM-IV or ICD-10 diagnosis of MDD, Depressive Episode, or Recurrent Depressive Disorder following SCID I, HDRS29, MADRS and BDI-II\n- Satisfactory general health as determined by past medical history, physical examination, vital signs at screening\n- 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\n- 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).\n- Sufficient visual and auditory performance for neuropsychological testing\n- 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.\n- Potential patients must be able to communicate well with the investigator and comply with the requirements of the study\n- Only participants who are legally authorized to give informed consent will be included in the present study."}

Exclusion criteria

• {"criterion_text":"- Depressed patients: Presence of any severe / unstable neurological, somatic or psychiatric comorbidity\n- Healthy controls: Therapy with any kind of psychotropic medication within the last 3 months\n- Antidepressive trials with deep brain stimulation (DBS), electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) or Ketamine\n- 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\n- Failure to comply with the study protocol or follow the instructions of the investigators\n- Positive urine pregnancy test\n- Known pregnancy or lactation\n- MRI scan that shows evidence of stroke, infarct, or other space-occupying lesion or structural abnormality\n- History of any other drug or alcohol abuse or misuse\n- 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\n- Evidence from an Allen test of incomplete communication between the radial and ulnar artery, in either hand\n- Healthy controls: Any unstable / severe psychiatric disease or any severe / unstable neurological or somatic disease\n- Significant radiation exposure (>5 mSv) in the frame of participation in trials within the past 10 years\n- Presence of psychotic symptoms\n- Acute suicidality\n- Any contraindication for magnetic resonance or PET imaging\n- Presence of any metallic implant in the head\n- 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)\n- 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\n- Depressed patients: Therapy with dopaminergic antidepressants including bupropion or other dopaminergic psychotropic agents (antipsychotics, stimulants, etc.) within the last 3 months"}

Primary endpoints

• {"endpoint_text":"- Reward-specific changes of dopamin-synthesis","definition_or_measurement_approach":"Measured using PET quantification of dopamine synthesis in the nucleus accumbens (NAcc) during the Monetary Incentive Delay Task (reward-specific PET assessment)."}

Secondary endpoints

• {"endpoint_text":"- To analyze the relationship between reward-specific dopamine synthesis and fMRI activation across healthy volunteers and patients with MDD","definition_or_measurement_approach":"Correlation/analysis between PET-derived reward-specific dopamine synthesis rates and fMRI activation during the Monetary Incentive Delay Task across groups."}
• {"endpoint_text":"- To identify remission rates in MDD patients being treated with either escitalopram OR bupropion in a longitudinal design","definition_or_measurement_approach":"Identification of remission rates during and after treatment using clinical rating scales (e.g., HDRS29, MADRS, BDI-II) in a longitudinal treatment design."}
• {"endpoint_text":"- Test-retest reliability for the quantification of dopamine synthesis rates in healthy volunteers","definition_or_measurement_approach":"Assessment of test-retest reliability of PET quantification of dopamine synthesis using repeated PET scans in healthy controls."}

Other endpoints

• {"endpoint_text":"- Magnetic Resonance Spectroscopy and Imaging (optional): - To investigate the potential relationship between reward-specific nucleus accumbens dopamine synthesis and GABA-/glutamatergic neurotransmission","definition_or_measurement_approach":"Optional MRS/MRI modalities to measure GABA and glutamate levels and assess association with PET-derived NAcc dopamine synthesis."}
• {"endpoint_text":"- Magnetic Resonance Spectroscopy and Imaging (optional): -To reveal baseline differences in GABA-/glutamatergic neurotransmission between depressed and healthy subjects","definition_or_measurement_approach":"Optional baseline MRS measurements comparing GABA/glutamate between groups."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Optional longitudinal MRS to relate changes in GABA/glutamate to clinical outcomes after bupropion treatment."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Exploratory gut microbiome profiling to assess associations with PET-derived reward-specific NAcc dopamine synthesis."}
• {"endpoint_text":"- Microbiome Analysis (optional): - To assess whether bupropion alters gut microbial composition longitudinally","definition_or_measurement_approach":"Longitudinal microbiome sampling to detect changes in composition associated with bupropion treatment."}
• {"endpoint_text":"- Microbiome Analysis (optional): - To explore the predicitive value of baseline gut microbiome composition for antidepressant treatment efficacy with bupropion","definition_or_measurement_approach":"Exploratory analyses of baseline microbiome features as predictors of treatment response to bupropion."}
• {"endpoint_text":"- Microbiome Analysis (optional): - To explore associations between longitudinal changes in gut microbiome composition and clinical treatment response after bupropion treatment","definition_or_measurement_approach":"Association analyses between longitudinal microbiome changes and clinical outcome measures following bupropion therapy."}

Austria

Earliest CTIS Part Ii Submission Date

18-11-2024

Latest Decision Or Authorization Date

13-03-2026

Processing Time Days

480

Number Of Sites

1

Number Of Participants

100

Primary sponsor

Full Name

Medical University Of Vienna

Organisation Type

Educational Institution

Country Of Registered Address

Austria