CYCLOSERINE for Major depressive disorder (MDD)|Major depression

Inclusion criteria

• {"criterion_text":"- The subject has given their written consent to participate in the trial."}
• {"criterion_text":"- For female subjects of fertile age, adequate contraception should be used."}
• {"criterion_text":"- Signed informed consent"}
• {"criterion_text":"- Are at least 18 years old at the time of written informed consent"}
• {"criterion_text":"- Are able to read, speak, and understand Swedish"}
• {"criterion_text":"- Are able and willing to adhere to study requirements, including attending all study visits, preparatory and follow-up sessions, and completing all study evaluations"}
• {"criterion_text":"- Are able to swallow capsules"}
• {"criterion_text":"- Meet ICD-10 criteria for a diagnosis of a major depressive disorder and are currently experiencing a major depressive episode of at least a 30-day duration at the time of the screening"}
• {"criterion_text":"- Have sustained moderate-severe depression symptoms at screening, as defined by a screening MADRS total score ≥ 20."}
• {"criterion_text":"- Failure to achieve clinical response with at least one adequate trial of a first line antidepressant medication or psychotherapy."}
• {"criterion_text":"- Unchanged antidepressant medications for 4 weeks prior to enrollment and the patient have no intention of changing medications during the first 28 days of the study."}

Exclusion criteria

• {"criterion_text":"- Have intracardial lines (pacemaker or ICD) intracranial metallic implant"}
• {"criterion_text":"- Current pregnancy, or intend to become pregnant during the study or who are currently nursing."}
• {"criterion_text":"- Currently receive electroconvulsive therapy (ECT)"}
• {"criterion_text":"- Meet ICD-10 criteria for schizophrenia spectrum or other psychotic disorders, including MDD with psychotic features (except substance/medication-induced or due to another medical condition), or Bipolar I Disorder, Bipolar II Disorder and bipolar disorder NOS, or a lifetime diagnosis of schizophrenia spectrum or other psychotic disorders"}
• {"criterion_text":"- Meet ICD-10 criteria for a moderate or severe alcohol or drug use disorder (excluding caffeine & nicotine). Participants with a diagnosis of alcohol or drug use disorder within the past 3 months will be excluded"}
• {"criterion_text":"- Have presence of any psychiatric condition or symptom judged by the PI (or designee) to be a more significant clinical problem than MDD for the participant"}
• {"criterion_text":"- Have any physical or psychological symptom, medication or other relevant finding at Screening or Baseline, based on the clinical judgment of clinical/medical study personnel, that would make a participant unsuitable for the study"}
• {"criterion_text":"- Have an allergy or intolerance to any of the materials contained in either drug product"}
• {"criterion_text":"- Have an unstable medical condition"}
• {"criterion_text":"- Have epilepsy"}
• {"criterion_text":"- Have renal failure"}
• {"criterion_text":"- Have porphyria"}
• {"criterion_text":"- Use bensodiazepines"}
• {"criterion_text":"- Use dextrometorphan"}
• {"criterion_text":"- Use memantine"}
• {"criterion_text":"- Use ketamine"}

Primary endpoints

• {"endpoint_text":"- Between-group difference in change of blinded rater MADRS total score from baseline to Day 28 (21-35) after first treatment day (interview by blinded external rater via video consultation documented on item level in eCRF).","definition_or_measurement_approach":"Change in MADRS total score assessed by a blinded external rater via video consultation, documented item-level in the eCRF; comparison between groups from baseline to Day 28 with window Day 21-35."}

Secondary endpoints

• {"endpoint_text":"- Change in observer rated depressive symptoms (MADRS) to treatment day 12 and 180 and Clinical Global Impression (CGI) at day 12, 28, and 180","definition_or_measurement_approach":"Observer-rated MADRS at specified time points (day 12 and day 180) and CGI at days 12, 28, 180."}
• {"endpoint_text":"- Response and remission rates at all time points on observer (MADRS) and self-rated depressive symptoms Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR)","definition_or_measurement_approach":"Response and remission rates derived from MADRS (observer) and QIDS-SR (self-report) at all scheduled time points."}
• {"endpoint_text":"- Survival time to initiation of new antidepressant treatment, hospitalization or death during the whole study period (until day 180)","definition_or_measurement_approach":"Time-to-event analysis measuring time from baseline to initiation of new antidepressant treatment, hospitalization, or death up to day 180."}
• {"endpoint_text":"- Change in score from baseline to Day 5, 12, 42, and 180 (end of study) self-rated depressive symptoms (QIDS-SR); Intensity in Suicidal Ideation from Columbia Suicide Severity Rating Scale (ISI-CSSR); anxiety symptoms, General Anxiety Disorder 7 (GAD-7); functioning, Sheehan Disability Scale (SDS); general health perception, EQ-5D-5L","definition_or_measurement_approach":"Changes from baseline in QIDS-SR at days 5,12,42,180; suicidal ideation intensity via C-SSRS; GAD-7 for anxiety; SDS for functioning; EQ-5D-5L for health perception."}
• {"endpoint_text":"- Change in cognitive functioning (THINC-it); pre-attentive stimuli detection, Mismatch Negativity (MMN); frontal oxygenation (fNIRS); resting EEG measures including frequency spectra, microstates, and aperiodic activity.","definition_or_measurement_approach":"Cognitive function assessed with THINC-it; neurophysiological measures include MMN (EEG), frontal fNIRS oxygenation, and resting EEG analyses (frequency spectra, microstates, aperiodic activity)."}

Sweden

Earliest CTIS Part Ii Submission Date

22-08-2025

Latest Decision Or Authorization Date

15-09-2025

Processing Time Days

24

Number Of Sites

6

Number Of Participants

105

Primary sponsor

Full Name

Region Uppsala

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Sweden