D-Cycloserine+iTBS PK Study

Major Depressive Disorder Clinical Trial

Official title: A Pharmacokinetic Study of Adjunctive D-cycloserine to Intermittent Theta Burst Stimulation in Major Depressive Disorder

Status Completed

Clinical Trial Summary

Background & Rationale: Major Depressive Disorder (MDD) is a common and debilitating illness that that commonly does not respond to conventional treatments. Transcranial magnetic stimulation (TMS) and intermittent theta-burst stimulation (iTBS) are non-invasive neurostimulation treatments for depression that are Health Canada approved. These work by generating magnetic fields outside of the body to change the activity of brain cells to change how the brain works. They have a very favorable profile, with many patients experiencing improvement with minimal side effects.

The investigators recently completed a study pairing iTBS with an FDA approved medication that was chosen because it might enhance iTBS improvements. This medication is called D-cycloserine, an old antibiotic that is rarely used in modern times. Years after it stopped being useful as an antibiotic, scientists recognized other properties that the molecule has, and it is some of these that make it interesting to pair with iTBS. When the investigators did so, they found that compared to iTBS with a placebo, participants who received iTBS+D-cycloserine were more likely to benefit from treatment.

In this original study, all participants received a fixed dose of 100mg daily. This means that people of very different sizes could have had different drug levels, and the investigators do not know how that impacted outcomes. With this study, there will be no placebo condition because the purpose is to understand whether dosing according to weight matters.

Research Question and Objectives: To describe the pharmacokinetic profile of 100mg oral D-cycloserine and weight-based oral D-cycloserine dosed 25mg/17.5kg among individuals with depression undergoing non-invasive intermittent theta-burst stimulation to the left dorsolateral prefrontal cortex (DLPFC) in Major Depressive Disorder.

Clinical Trial Description

Methods: An open-label study of D-cycloserine (DCS) pharmacokinetics will be performed in patients undergoing iTBS to the left DLPFC as a treatment for Major Depressive Disorder. Twelve patients (males and females aged 18-65, with a score ≥18 on the Hamilton Rating Scale for Depression-17 items, and stable pharmacological and psychological regimens) with an acute Major Depressive Episode will be recruited. Bloodwork and an echocardiogram will be obtained prior to the initiation of the study, and enrollment in the study will be contingent on normal lab results.

Prior to initiating iTBS treatment, participants will receive one oral dose of 100mg DCS. A pharmacokinetic curve will be generated from D-Cycloserine levels obtained at 6 timepoints; pre-ingestion, +30 mins, + 60 mins, + 90mins, +120mins and +24 hrs.

Participants will receive iTBS daily for 4 weeks (20 sessions). All participants will be provided with weight-based dosing of DCS to take 120 minutes prior to each iTBS session. Serum levels of weight-based DCS dosing will be measured by blood draws at several time points throughout iTBS treatment. Specifically, a pharmacokinetic curve will be generated on Day 1 of iTBS treatment from D-Cycloserine levels obtained at 6 timepoints; pre-ingestion, +30 mins, + 60 mins, + 90mins, +120mins and +24 hrs. Additional time points will be obtained prior to and 120 minutes after the fifth dose (Day 5 of TMS) and prior to and 120 minutes after the sixth dose (Day 6 of TMS, corresponding to the beginning of the second week of TMS).

Antidepressant effects will be quantified using the Montgomery Asberg Depression Rating Scale, a gold standard clinician rated instrument. Participants will complete a short battery of cognitive tests at the beginning and end of the study. Blood work and echocardiogram will be repeated after 4 weeks to confirm safety of low-dose DCS.

Participants will return to the lab for a follow-up assessment 4 weeks after they have finished the TMS protocol (week 8). ;

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

• NCT number: NCT05731323
• Study type: Interventional
• Source: University of Calgary
• Status: Completed
• Phase: Phase 1
• Start date: October 12, 2022
• Completion date: June 22, 2023