D-Cycloserine Augmentation of Intermittent Theta Burst Stimulation (iTBS) in Depression (COGENT)

NCT05591677 | Active Not Recruiting Phase 2

• 1 other identifier: 567-22
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to investigate if the drug D-Cycloserine (DCS) improves the antidepressant effects of Intermittent Theta Burst Stimulation (iTBS), a non-invasive brain stimulation therapy, in patients with Major Depressive Disorder (MDD). The main questions it aims to answer are:

• Whether taking DCS prior to iTBS therapy will be more effective in improving depressive symptoms than iTBS therapy alone.
• Compare the effect of DCS 100mg/day versus 50mg/day on depressive symptoms.
• Test the safety and tolerability of DCS. Participants will take either 50mg DCS per day, 100mg DCS or placebo prior to each iTBS treatment session. iTBS treatment will be administered daily, 5 days a week for 4 weeks. Clinical measures will be conducted at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Rate of treatment response as per Montgomery Åsberg Depression Rating Scale (MADRS)

  Clinical treatment response defined as \>/= 50% reduction in MADRS scores from baseline to primary study endpoint. Clinician-administered depression rating scale. The overall score ranges from 0 - 60. Cutoff points are 0-6 = normal, 7-9 = mild depression, 20-34 = moderate depression, \>34 = severe depression.

  Determined at Week 4 (primary study endpoint)

Secondary Outcomes (7)

• Change in Montgomery Åsberg Depression Rating Scale (MADRS)

  Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.

• Change in Clinical Global Impression (CGI)

  Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.

• Change in Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR)

  Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.

• Beck's Anxiety Inventory (BAI)

  Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.

• International Trauma Questionnaire (ITQ)

  Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.

Study Arms (3)

Active iTBS + active DCS 50mg/day

ACTIVE COMPARATOR

Active iTBS (600 pulses), 5 days/week x 4 weeks + active DCS 50mg/day x 2 weeks, taken 2-hours prior to scheduled iTBS treatment.

Drug: D-Cycloserine; Device: Intermittent Theta Burst Stimulation

Active iTBS + active DCS 100mg/day

ACTIVE COMPARATOR

Active iTBS (600 pulses), 5 days/week x 4 weeks + active DCS 100mg/day x 2 weeks, taken 2-hours prior to scheduled iTBS treatment.

Drug: D-Cycloserine; Device: Intermittent Theta Burst Stimulation

Active iTBS + placebo

PLACEBO COMPARATOR

Active iTBS (600 pulses), 5 days/week x 4 weeks + placebo x 2 weeks, taken 2-hours prior to scheduled iTBS treatment.

Device: Intermittent Theta Burst Stimulation

Interventions

D-Cycloserine DRUG

D-cycloserine (DCS) is a partial NMDA receptor agonist that has demonstrable impact on rTMS and TBS's neuromodulatory effects. Participants will be asked to orally ingest one capsule 2-hours prior to their scheduled iTBS treatment time.

Active iTBS + active DCS 100mg/day; Active iTBS + active DCS 50mg/day

Intermittent Theta Burst Stimulation DEVICE

Intermittent Theta Burst Stimulation (iTBS) will be administered with a magnetic stimulator using a figure-of-8 coil or equivalent FDA-approved device. Initial treatment coil localisation and individual calibration of stimulation intensity will be conducted by TMS-trained investigators/staff using standard approaches.67,68 Stimulation intensity will be at 90% of the individual's calibrated resting motor threshold. iTBS treatment session delivers 600 pulses and is approximately 3½ minutes in duration. The total pulse number applied over a course of 20 treatments will be 12,000. This regimen is analogous with the iTBS protocol approved by the US FDA to treat TRD.

Active iTBS + active DCS 100mg/day; Active iTBS + active DCS 50mg/day; Active iTBS + placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of major depressive episode (MDE), in accordance with the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5), in the context of unipolar major depressive disorder or bipolar affective disorder.
• years or older in age.
• Treatment resistant depression at Stage II of the Thase and Rush classification.56
• Baseline Montgomery Åsberg Depression Rating Scale score of ≥ 20 (moderate-to-severe depression severity).57,58
• No increase or initiation of new antidepressant therapy in the four weeks prior to screening.
• Demonstrated capacity to give informed consent.

You may not qualify if:

• Inability to provide informed consent.
• Medically unstable patients at the discretion of the investigator.
• Concomitant neurological disorder or a history of a seizure disorder.
• Participants who are pregnant.
• Current substance use meeting DSM-5 criteria for substance use disorder.
• Per DSM-5, had ever met diagnostic criteria for schizophrenia, schizoaffective disorder, schizophreniform disorder or delusional disorder as assessed by the Mini-International Neuropsychiatric Interview (MINI) at the time of screening.
• Diagnosis of any other mental disorder that is the participant's primary diagnosis or main mental health syndrome of concern at the time of screening, which may significantly affect psychiatric status and assessed as likely to impact trial participation, in the clinical judgement of the investigator.

Sponsors & Collaborators

• The Alfred: lead
• Gold Coast Hospital and Health Service: collaborator
• Blue Bell Health, Australia: collaborator

Study Sites (1)

Monash Alfred Psychiatry Research Centre

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Cycloserine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oxazolidinones; Oxazoles; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Leo Chen, MBBS PhD FRANZCP

  The Alfred

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head, Clinical TMS and Psychopharmacology Research Units, Monash Alfred Psychiatry Research Centre (MAPrc)

Study Record Dates

• First Submitted: October 16, 2022
• First Posted: October 24, 2022
• Study Start: April 21, 2023
• Primary Completion (Estimated): May 29, 2026
• Study Completion (Estimated): May 29, 2026
• Last Updated: December 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)