Major Depressive DisorderPhase 2NCT05591677

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

A Phase 2 study testing D-Cycloserine and Intermittent Theta Burst Stimulation in people with Major Depressive Disorder, run by The Alfred at 1 site in Australia.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial 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). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Major Depressive Disorder
What is being tested?: D-Cycloserine and Intermittent Theta Burst Stimulation
Type of treatment: Pill or oral medicine, Medical device
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 180 participants
Where: 1 siteAustralia
Study dates: 21 Apr 2023to 29 May 2026
Phase: Phase 2
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.
18 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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

Australia1 site

Monash Alfred Psychiatry Research Centre
Melbourne, Victoria, 3004

Other trials in Australia

About this study

Official title: D-Cycloserine Augmentation of Intermittent Theta Burst Stimulation (iTBS) in Depression: A Multi-Site, Randomised, Placebo-Controlled Trial (COGENT)

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.

Read the detailed description

Major Depressive Disorder (MDD) is a common and debilitating condition with high rates of treatment resistance. Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for treatment-resistant depression with few adverse effects. Intermittent Theta Burst Stimulation (iTBS) is a time-efficient form of rTMS with evidence base in the treatment of treatment-resistant depression (TRD). The most commonly supported understanding of iTBS's mechanism of action appear to be its strengthening of connections between networks of neurons, which is modulated by the N-methyl-D-aspartate (NMDA) receptor. D-cycloserine (DCS) is a partial NMDA receptor agonist that has demonstrable impact on rTMS and TBS's neuromodulatory effects. This study protocol proposes the conduct of a prospective multi-site, parallel-arm design, randomized, double-blinded, placebo-controlled clinical trial to investigate DCS augmentation of iTBS in MDD. We will investigate if adjuvant DCS 50mg or 100mg/day might have superior iTBS antidepressant augmentation effects.

Conditions: Major Depressive Disorder
Being tested: D-Cycloserine, Intermittent Theta Burst Stimulation
Medical subject headings: Depressive Disorder, Major

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

D-CycloserineDrug
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.
Intermittent Theta Burst StimulationDevice
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.

Study groups in NCT05591677
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: Device: Intermittent Theta Burst Stimulation

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Determined at Week 4 (primary study endpoint)

Secondary outcomes (7)

Change in Montgomery Åsberg Depression Rating Scale (MADRS)
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.
Measured: Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.
Change in Clinical Global Impression (CGI)
Clinician assessment of overall illness severity and global functioning. The CGI-Severity scale is clinician rated from 1-7 representing 'Not at all ill' to 'Severely ill'. The CGI-Improvement scale is also rated 1-7, representing the range between 'Very much improved' and 'Very much worse'.
Measured: 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)
Self-reported symptom rating scale for depression severity. Severity of depression can be judged based on the total score. 1-5 = No depression 6-10 = Mild depression 11-15 = Moderate depression 16-20 = Severe depression 21-27 = Very severe depression.
Measured: Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.
Beck's Anxiety Inventory (BAI)
Self-reported symptom rating scale for anxiety severity. The score range is 0-63. A total score of 0-7 is considered minimal range, 8-15 is mild, 16-25 is moderate, and 26-63 is severe.
Measured: Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.
International Trauma Questionnaire (ITQ)
Self-reported symptom rating of trauma-related symptoms and their severity. All ITQ items are answered on a 5-point Likert scale ranging from 0 (Not at all) to 4 (Extremely).
Measured: Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.
Beck's Scale for Suicide Ideation (BSS)
Self-reported symptom rating scale for suicidal ideation. Scores range from 0 to 38, a higher score indicating a higher level of suicide ideation.
Measured: Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.
Change in World Health Organization Quality of Life (WHOQOL-BREF)
Self-reported rating scale of quality of life. Domains scores are calculated to range from 0-20 and scaled in a positive direction (ie. higher scores denote higher quality of life).
Measured: Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Apr 202329 May 2026

First posted24 Oct 2022
Study start21 Apr 2023
Primary completion29 May 2026 (estimated)
Study completion29 May 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 180 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05591677
Sponsor's protocol ID: 567-22
Status last verified: Nov 2025
First submitted: 16 Oct 2022
Last updated: 4 Dec 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Major Depressive Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: D-Cycloserine Augmentation of Intermittent Theta Burst Stimulation (iTBS) in Depression: A Multi-Site, Randomised, Placebo-Controlled Trial (COGENT)
ClinicalTrials.gov ID: NCT05591677
Acronym / sponsor ID: 567-22
Conditions: Major Depressive Disorder
Phase: Phase 2
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 180 participants (estimated)
Lead sponsor: The AlfredUniversity, hospital or other
Collaborators: Blue Bell Health, Australia, Gold Coast Hospital and Health Service
Study start: 21 Apr 2023 (actual)
Primary completion: 29 May 2026 (estimated)
Study completion: 29 May 2026 (estimated)
First posted: 24 Oct 2022 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Active iTBS + active DCS 50mg/day	Active comparator	Drug: D-Cycloserine, Device: Intermittent Theta Burst StimulationActive iTBS (600 pulses), 5 days/week x 4 weeks + active DCS 50mg/day x 2 weeks, taken 2-hours prior to scheduled iTBS treatment.
Active iTBS + active DCS 100mg/day	Active comparator	Drug: D-Cycloserine, Device: Intermittent Theta Burst StimulationActive iTBS (600 pulses), 5 days/week x 4 weeks + active DCS 100mg/day x 2 weeks, taken 2-hours prior to scheduled iTBS treatment.
Active iTBS + placebo	Placebo comparator	Device: Intermittent Theta Burst StimulationActive iTBS (600 pulses), 5 days/week x 4 weeks + placebo x 2 weeks, taken 2-hours prior to scheduled iTBS treatment.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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.
18 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.

Key exclusion criteria (7 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
D-CycloserineD-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.	Drug	Active iTBS + active DCS 100mg/day, Active iTBS + active DCS 50mg/day
Intermittent Theta Burst StimulationIntermittent 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.	Device	Active iTBS + active DCS 100mg/day, Active iTBS + active DCS 50mg/day, Active iTBS + placebo

Primary outcome

Rate of treatment response as per Montgomery Åsberg Depression Rating Scale (MADRS)
Time frame: Determined at Week 4 (primary study endpoint)
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.

7 secondary outcomes

Change in Montgomery Åsberg Depression Rating Scale (MADRS)
Time frame: Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.
Change in Clinical Global Impression (CGI)
Time frame: 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)
Time frame: Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.
Beck's Anxiety Inventory (BAI)
Time frame: Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.
International Trauma Questionnaire (ITQ)
Time frame: Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.
Beck's Scale for Suicide Ideation (BSS)
Time frame: Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.
Change in World Health Organization Quality of Life (WHOQOL-BREF)
Time frame: Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2025.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Leo Chen, MBBS PhD FRANZCP principal investigator

The Alfred

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing D-Cycloserine and Intermittent Theta Burst Stimulation in people with Major Depressive Disorder, run by The Alfred at 1 site in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 4 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of treatment response as per Montgomery Åsberg Depression Rating Scale (MADRS) (time frame: Determined at Week 4 (primary study endpoint)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05591677.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2025.