Adjunctive D-Cycloserine in Major Depressive Disorder
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): D-cycloserine; Transcranial Magnetic Stimulator; Placebo oral capsule
Intervention type(s): Drug; Device; Drug
Intervention description(s): Daily oral D-cycloserine 100mg during the blinded phase (10 days).; 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.; Daily oral placebo during the blinded phase (10 days).
Other intervention name(s): Seromycin
Intervention MeSH terms: Cycloserine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment