NCT03937596

Adjunctive D-Cycloserine in Major Depressive Disorder

A Randomized Placebo-controlled Trial of Adjunctive D-cycloserine in Repetitive Transcranial Magnetic Stimulation for Major Depressive Disorder

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (actual)
• Sponsor: University of Calgary · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

Transcranial magnetic stimulation (rTMS) is an approved treatment for depression. The purpose of this study is to test an adjunctive medication, D-cycloserine, in rTMS for depression using a placebo-controlled design. D-Cycloserine is a partial N-Methyl-D-Aspartate receptor (NMDAr) agonist, and therefore may enhance the effects of rTMS, however there is data to support and refute this hypothesis. Using a double-blind design, the investigators will randomize patients with Major Depressive Disorder to receive either daily low dose D-cycloserine or placebo in conjunction with rTMS to the left dorsolateral prefrontal cortex. After 10 treatments (2 weeks), this double-blind period will conclude and all participants will receive an additional 10 treatments (2 weeks) of rTMS without any adjuncts. The primary outcome will be improvement in clinician rated depressive symptoms at the conclusion of the study.

Detailed description

Major Depressive Disorder (MDD) is a common and debilitating illness. For an unacceptable proportion of patients, depressive symptoms remain impairing despite multiple treatments. Increasingly, non-invasive brain stimulation techniques are being explored as a means of targeting specific brain regions and networks that are implicated in depression. Repetitive transcranial magnetic stimulation (rTMS) is the non-invasive stimulation technique with the largest evidence base in MDD. Targeting the dorsolateral prefrontal cortex (DLPFC) with rTMS has proven an effective treatment for MDD, however as many as 2/3 of patients will not experience substantial improvement. Adjunctive agents are a potential strategy to improve patient outcomes. The objective of the proposed study is to determine the efficacy of adjunctive D-cycloserine with rTMS directed to the left dorsolateral prefrontal cortex (DLPFC) in acute Major Depressive Episodes. The investigators propose to utilize a stimulation protocol called the intermittent theta-burst protocol to study rTMS in conjunction with D-cyloserine using a randomized double-blind, placebo-controlled design with allocation concealment. Patients with Major Depressive Disorder will be randomized to receive 1) rTMS+cycloserine, or 2) rTMS+placebo in a 1:1 ratio for two weeks (10 sessions). At the conclusion of the 2-week blinded augmentation phase, patients will continue to receive two weeks of rTMS without an augmentation agent or placebo. The primary outcome measures will be improvement in depression as measured by change in Montgomery Asberg Depression Rating Scale (MADRS). In addition, the investigators will also be looking at the improvement of other clinical outcome measures, quality of life and changes in brain functional dynamics, as assessed with functional Magnetic Resonance Imaging (MRI), and metabolites, as assessed by Magnetic Resonance (MR) Spectroscopy.

Conditions

• Major Depressive Disorder

Interventions

Type	Name	Description
DRUG	D-cycloserine	Daily oral D-cycloserine 100mg during the blinded phase (10 days).
DEVICE	Transcranial Magnetic Stimulator	Repetitive Transcranial magnetic stimulation (rTMS) will be delivered using a MagPro X100 device with B70 coil and the intermittent theta burst (iTBS) protocol to the left dorsolateral prefrontal cortex. Participants will receive daily treatments (Monday-Friday) over four weeks.
DRUG	Placebo oral capsule	Daily oral placebo during the blinded phase (10 days).

Timeline

• Start date: 2019-12-01
• Primary completion: 2020-12-24
• Completion: 2020-12-24
• First posted: 2019-05-06
• Last updated: 2022-01-10

Locations

1 site across 1 country: Canada

Regulatory

• FDA-regulated drug study
• FDA-regulated device study