D-Cycloserine+iTBS PK Study
Major Depressive Disorder
About this trial
This is an interventional treatment trial for Major Depressive Disorder
Eligibility Criteria
Inclusion Criteria: Males and females aged 18 to 65 years are competent to consent to treatment have a confirmed diagnosis of DSM-5 criteria Major Depressive Disorder with a current episode of at least moderate severity of depression, single or recurrent have failed to achieve a clinical response to one adequate trial of antidepressant medication within the current episode, or been unable to tolerate antidepressant medications. have current episode of at least moderate severity of depression, as defined by a score ≥ 18 on the HAMD-17 item have had no change in dose, or initiation of any psychotropic medication in the 4 weeks prior to randomization are able to adhere to the treatment schedule pass the TMS adult safety screening (TASS) questionnaire have had blood work (complete blood count, electrolytes, BUN, creatinine, eGFR, AST, ALT and GGT, and ECG) within the reference range. Female participants must have a negative pregnancy test. Exclusion Criteria: Allergy to cycloserine. have failed adequate trials of ≥4 antidepressant treatments in the current episode. have an alcohol or substance use disorder within the last 3 months have suicidal ideation (score of 4 ≥ on item 10 of MADRS) are at a significant risk of harm to themselves or others current symptoms of psychosis history of psychosis are currently pregnant, breast feeding or plan to become pregnant over the duration of the study have a diagnosis of other primary psychiatric diagnoses as assessed by a study investigator to be primary and causing greater impairment than Major Depressive Disorder. have failed a course of ECT in the current episode. Previous ECT treatment outside of the current episode does not influence inclusion. history of non-response to TMS treatment. have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of epilepsy, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than or equal to 5 minutes have concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed if participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study are currently (or in the last 4 weeks) taking any benzodiazepine, cyclopyrrolone, gabapentin/pregabalin or anticonvulsant due to the potential to limit TMS efficacy have an exclusion criteria for MRI: Those with a history of cranial, thoracic or abdominal surgery, with pacemakers, artificial joints or other metallic implants will be excluded from the MRI scan. Subjects that have agreed to participate in the MRI portion of the study will be pre-screened for any potential metal fragments in the body (particularly in the orbits) if they have had any history of doing metal work or have been involved in use/deployment of ammunitions/explosives, welding, piping etc). are being currently treated with ethionamide or isoniazid (contraindicated with D-cycloserine)
Sites / Locations
- University of Calgary
Arms of the Study
Arm 1
Experimental
D-Cycloserine
Prior to initiating TMS therapy, participants will orally ingest a capsule containing 100mg of the antibiotic d-cycloserine. During TMS therapy, participants will orally ingest a capsule containing a weight-based dose of the antibiotic d-cycloserine (dosed 25mg/17.5kg body weight) daily (Monday-Friday) for 4 weeks of rTMS treatment (20 sessions).