Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001359729
Ethics application status
Approved
Date submitted
30/09/2022
Date registered
24/10/2022
Date last updated
16/01/2024
Date data sharing statement initially provided
24/10/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
D-Cycloserine Augmentation of Intermittent Theta Burst Stimulation (iTBS) in Depression
Scientific title
D-Cycloserine Augmentation of Intermittent Theta Burst Stimulation (iTBS) in Depression: A Multi-Site, Randomised, Placebo-Controlled Trial
Secondary ID [1] 308078 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Major Depressive Disorder 327769 0
Condition category
Condition code
Mental Health 324838 324838 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All eligible participants will receive iTBS therapy, which will be administered at the Monash Alfred Psychiatry Research Centre (MAPrc) by trained research staff. TMS will be administered with a Neurosoft-MS/D magnetic stimulator. Stimulation is applied to the left dorsolateral prefrontal cortex (DLPFC) and stimulation intensity will be at 90% of the individual’s calibrated resting motor threshold. Each iTBS treatment session delivers 600 pulses and is approximately 3½ minutes in duration. iTBS treament sessions will be administered daily, 5 days a week for 4 weeks.
Participants in the treatment arm will be required to ingest an oral capsule of either 50mg of D-Cycloserine (DCS) or 100mg DCS 2-hours prior to each iTBS treatment session (i.e. 5 days a week for 4 weeks). The recording of self-reported ingestion times of DCS will be used to monitor adherence with the study protocol.
Intervention code [1] 324525 0
Treatment: Drugs
Intervention code [2] 324526 0
Treatment: Devices
Comparator / control treatment
All eligible participants will receive iTBS therapy, which will be administered at the Monash Alfred Psychiatry Research Centre (MAPrc) by trained research staff. Stimulation is applied to the left dorsolateral prefrontal cortex (DLPFC) and stimulation intensity will be at 90% of the individual’s calibrated resting motor threshold. iTBS treament sessions will be administered daily, 5 days a week for 4 weeks.
Participants in the control arm will be required to orally ingest placebo capsules containing Methylcellulose 2-hours prior to each iTBS treatment session (i.e. 5 days a week for 4 weeks). The recording of self-reported ingestion times of the placebo will be used to monitor adherence with the study protocol.
Control group
Placebo

Outcomes
Primary outcome [1] 332653 0
Montgomery Åsberg Depression Rating Scale (MADRS)
Timepoint [1] 332653 0
Baseline and at the ends of weeks 1, 2, 3 and 4 of treatment
Secondary outcome [1] 414244 0
Clinical Global Impression (CGI)
Timepoint [1] 414244 0
Baseline and at the ends of weeks 1, 2, 3 and 4 of treatment
Secondary outcome [2] 414245 0
Quick Inventory of Depressive Symptomatology – Self Report (QIDS-SR)
Timepoint [2] 414245 0
Baseline and at the ends of weeks 1, 2, 3 and 4 of treatment
Secondary outcome [3] 414246 0
Beck’s Anxiety Inventory (BAI)
Timepoint [3] 414246 0
Baseline and at the ends of weeks 1, 2, 3 and 4 of treatment
Secondary outcome [4] 414247 0
The International Trauma Questionnaire (ITQ)
Timepoint [4] 414247 0
Baseline and at the ends of weeks 1, 2, 3 and 4 of treatment
Secondary outcome [5] 414248 0
Beck’s Scale for Suicide Ideation (BSS)
Timepoint [5] 414248 0
Baseline and at the ends of weeks 1, 2, 3 and 4 of treatment
Secondary outcome [6] 414249 0
World Health Organization Quality of Life (WHOQOL-BREF)
Timepoint [6] 414249 0
Baseline and at the ends of weeks 1, 2, 3 and 4 of treatment

Eligibility
Key inclusion criteria
1. 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.
2. 18 years or older in age.
3. Treatment resistant depression at Stage II of the Thase and Rush classification.
4. Baseline Montgomery Åsberg Depression Rating Scale score of greater than or equal to 20 (moderate-to-severe depression severity).
5. No increase or initiation of new antidepressant therapy in the four weeks prior to screening.
6. Demonstrated capacity to give informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Inability to provide informed consent.
2. Medically unstable patients at the discretion of the investigator.
3. Concomitant neurological disorder or a history of a seizure disorder.
4. Participants who are pregnant.
5. Current substance use meeting DSM-5 criteria for substance use disorder.
6. Per DSM-5, had ever met diagnostic criteria for schizophrenia, schizoaffective disorder, schizophreniform disorder or delusional disorder as assessed by the MINI at the time of screening.
7. Diagnosis with antisocial, paranoid, schizoid or schizotypal personality disorder as per DSM-5 criteria and any other personality disorder at screening that significantly affects current psychiatric status and assessed as likely to impact trial participation, in the clinical judgement of investigator.
8. Diagnosis of any other mental disorder (in addition to those as described in Exclusion Criteria 5, 6 and 7) that is the participant’s primary diagnosis at the time of screening, in the clinical judgement of the investigator.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will be conducted at a central administration site (Alfred Hospital). Allocation will be concealed using sealed opaque envelopes and given to each site, to be opened after each participant's trial completion.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation to one of the three treatment arms will occur via the generation of a single computer number sequence (no stratification).
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/12/2022
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
180
Accrual to date
0
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 312332 0
Other
Name [1] 312332 0
Monash Alfred Psychiatry Research Centre
Country [1] 312332 0
Australia
Primary sponsor type
Hospital
Name
Alfred Health
Address
55 Commercial Rd, Melbourne VIC 3004
Country
Australia
Secondary sponsor category [1] 313893 0
None
Name [1] 313893 0
Address [1] 313893 0
Country [1] 313893 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311699 0
Alfred Human Research and Ethics Committee
Ethics committee address [1] 311699 0
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 311699 0
Australia
Date submitted for ethics approval [1] 311699 0
26/09/2022
Approval date [1] 311699 0
06/12/2022
Ethics approval number [1] 311699 0

Summary
Brief summary
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 TRD with few adverse effects. Intermittent theta burst stimulation (iTBS) is a novel and time-efficient form of rTMS with evidence base in the treatment of treatment-resistant depression. The drug D-cycloserine (DCS) is a has demonstrable impact on rTMS and iTBS’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 effects. We hypothesise that iTBS administered 2-hours after ingestion of DCS 50mg or 100mg will be more effective in treating depressive symptoms compared with iTBS administered 2-hour after ingestion of placebo.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 122046 0
Dr Leo Chen
Address 122046 0
Monash Alfred Psychiatry Research Centre
Level 4, 607 St Kilda Rd
Melbourne VIC 3004
Country 122046 0
Australia
Phone 122046 0
+61 3 9076 6564
Fax 122046 0
Email 122046 0
leo.chen@monash.edu
Contact person for public queries
Name 122047 0
Dr Elizabeth Thomas
Address 122047 0
Monash Alfred Psychiatry Research Centre
Level 4, 607 St Kilda Rd
Melbourne VIC 3004
Country 122047 0
Australia
Phone 122047 0
+61 3 9076 5172
Fax 122047 0
Email 122047 0
tms-trials@monash.edu
Contact person for scientific queries
Name 122048 0
Dr Leo Chen
Address 122048 0
Monash Alfred Psychiatry Research Centre
Level 4, 607 St Kilda Rd
Melbourne VIC 3004
Country 122048 0
Australia
Phone 122048 0
+61 3 9076 6564
Fax 122048 0
Email 122048 0
leo.chen@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.