Clinical trial NCT05591677: D-Cycloserine Augmentation of Intermittent Theta Burst Stimulation (iTBS) in Depression (COGENT)
Official title: D-Cycloserine Augmentation of Intermittent Theta Burst Stimulation (iTBS) in Depression: A Multi-Site, Randomised, Placebo-Controlled Trial (COGENT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Major Depressive Disorder
Lead sponsor: The Alfred
Sponsor class: OTHER
Collaborators: name: Blue Bell Health, Australia
name: Gold Coast Hospital and Health Service
First posted: 2022-10-24
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Rate of treatment response as per Montgomery Åsberg Depression Rating Scale (MADRS)
timeFrame: Determined at Week 4 (primary study endpoint)
Secondary outcomes:
measure: Change in Montgomery Åsberg Depression Rating Scale (MADRS)
timeFrame: Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.
measure: Change in Clinical Global Impression (CGI)
timeFrame: Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.
measure: Change in Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR)
timeFrame: Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.
measure: Beck's Anxiety Inventory (BAI)
timeFrame: Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.
measure: International Trauma Questionnaire (ITQ)
timeFrame: Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.
measure: Beck's Scale for Suicide Ideation (BSS)
timeFrame: Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.
measure: Change in World Health Organization Quality of Life (WHOQOL-BREF)
timeFrame: Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Monash Alfred Psychiatry Research Centre
state: Victoria
Study officials:
affiliation: The Alfred
name: Leo Chen, MBBS PhD FRANZCP
role: PRINCIPAL_INVESTIGATOR
References: