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

The Alfred

Status and phase: Active, not recruiting; Phase 2

Conditions: Major Depressive Disorder

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

Study type: Interventional

Funder types: Other

Identifiers

NCT05591677

567-22

Details and patient eligibility

About

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.

Full 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.

Enrollment: 180 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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180 participants in 3 patient groups, including a placebo group

Active iTBS + active DCS 50mg/day

Active Comparator group

Description:

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.

Treatment:

Drug: D-Cycloserine

Device: Intermittent Theta Burst Stimulation

Active iTBS + active DCS 100mg/day

Active Comparator group

Description:

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.

Treatment:

Drug: D-Cycloserine

Device: Intermittent Theta Burst Stimulation

Active iTBS + placebo

Placebo Comparator group

Description:

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

Treatment:

Device: Intermittent Theta Burst Stimulation