- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05591677
D-Cycloserine Augmentation of Intermittent Theta Burst Stimulation (iTBS) in Depression (COGENT)
D-Cycloserine Augmentation of Intermittent Theta Burst Stimulation (iTBS) in Depression: A Multi-Site, Randomised, Placebo-Controlled Trial (COGENT)
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Kaila Bianco
- Phone Number: +61 3 9076 6564
- Email: tms-trials@monash.edu
Study Contact Backup
- Name: Violet Francis
- Phone Number: +61 3 9076 6564
- Email: tms-trials@monash.edu
Study Locations
-
-
Victoria
-
Melbourne, Victoria, Australia, 3004
- Recruiting
- Monash Alfred Psychiatry Research Centre
-
Contact:
- Jacqui Noonan
- Phone Number: +61 3 9076 6596
- Email: jacqui.noonan@monash.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Active iTBS + active DCS 50mg/day
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.
|
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 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 Comparator: Active iTBS + active DCS 100mg/day
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.
|
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 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.
|
Placebo Comparator: Active iTBS + placebo
Active iTBS (600 pulses), 5 days/week x 4 weeks + placebo x 2 weeks, taken 2-hours prior to scheduled iTBS treatment.
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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. |
Determined at Week 4 (primary study endpoint)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
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.
|
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.
|
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'.
|
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.
|
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.
|
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.
|
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.
|
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.
|
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).
|
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.
|
Self-reported symptom rating scale for suicidal ideation.
Scores range from 0 to 38, a higher score indicating a higher level of suicide ideation.
|
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.
|
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).
|
Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Leo Chen, MBBS PhD FRANZCP, The Alfred
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 567-22
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Major Depressive Disorder
-
York UniversityCentre for Addiction and Mental HealthSuspendedDisorder, Major DepressiveCanada
-
Shalvata Mental Health CenterUnknownMAjor Depressive DisorderIsrael
-
Seasons Biotechnology (Taizhou) Co., Ltd.CompletedMajor Depressive Disorder (MDD)India
-
Repurposed Therapeutics, Inc.Unknown
-
GlaxoSmithKlineCompletedMajor Depressive Disorder (MDD)United States
-
Seasons Biotechnology (Taizhou) Co., Ltd.CompletedMajor Depressive Disorder (MDDIndia
-
Gangnam Severance HospitalCompletedMajor Depressive Disorder(MDD)Korea, Republic of
-
University College, LondonCompletedUnipolar Major Depressive DisorderUnited Kingdom
-
Fundació Institut de Recerca de l'Hospital de la...Fondo de Investigacion SanitariaUnknown
-
AccexibleRecruitingMajor Depressive Disorder (MDD)Spain
Clinical Trials on D-Cycloserine
-
Mclean HospitalUniversity of MinnesotaCompletedSchizophrenia | Bipolar Disorder
-
University of Texas at AustinBoston University; Rush University Medical Center; Southern Methodist UniversityCompletedSocial Anxiety DisorderUnited States
-
University of OxfordNational Health Service, United KingdomUnknownChronic Obstructive Pulmonary DiseaseUnited Kingdom
-
Northwestern UniversityNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National...TerminatedChronic Prostatitis With Chronic Pelvic Pain SyndromeUnited States
-
Yale UniversityCompletedAlcohol DependenceUnited States
-
University of California, Los AngelesUnknownTraumatic Brain InjuryUnited States
-
US Department of Veterans AffairsCompleted
-
University of ArkansasNational Institute on Drug Abuse (NIDA)Completed
-
Northwestern UniversityTerminatedPain | Breast Cancer | NeurotoxicityUnited States
-
Hoffmann-La RocheCompletedHepatitis C, ChronicNew Zealand, Australia