Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 12 of 121 for:    Anti-Bacterial | CYCLOSERINE OR SEROMYCIN

Cycloserine rTMS Plasticity Augmentation in Depression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03511599
Recruitment Status : Recruiting
First Posted : April 30, 2018
Last Update Posted : September 14, 2018
Sponsor:
Information provided by (Responsible Party):
University of Calgary

Tracking Information
First Submitted Date  ICMJE April 18, 2018
First Posted Date  ICMJE April 30, 2018
Last Update Posted Date September 14, 2018
Actual Study Start Date  ICMJE September 3, 2018
Estimated Primary Completion Date September 3, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 27, 2018)
Motor evoked potential amplitude [ Time Frame: Baseline versus 90 minutes following theta-burst stimulation. ]
Change in the (electrical) amplitude of muscle responses to stimulation of the motor cortex will be recorded from the first dorsal interosseous muscle of the hand.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03511599 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2018)
  • Motor evoked potential dose-response curve [ Time Frame: Baseline versus 90 minutes after theta-burst stimulation. ]
    Motor evoked potentials at stimulus intensities ranging from 100-150% resting motor threshold, presented at random order.
  • Motor evoked potential dose-response curve [ Time Frame: Baseline versus 16 hours following theta-burst stimulation. ]
    Motor evoked potentials at stimulus intensities ranging from 100-150% resting motor threshold, presented at random order.
  • Motor evoked potential amplitude [ Time Frame: Baseline and the evolution over 90 minutes following theta-burst stimulation. ]
    Change in the (electrical) amplitude of muscle responses to stimulation of the motor cortex will be recorded from the first dorsal interosseous muscle of the hand.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 27, 2018)
  • Motor evoked potential dose-response curve [ Time Frame: The morning after theta-burst stimulation (16 hours). ]
    Motor evoked potentials at stimulus intensities ranging from 100-150% resting motor threshold, presented at random order.
  • Motor evoked potential amplitude [ Time Frame: Baseline versus 16 hours following theta-burst stimulation. ]
    Amplitude of the first dorsal interosseous muscle TMS evoked potential.
Current Other Pre-specified Outcome Measures
 (submitted: April 27, 2018)
  • Safety outcomes [ Time Frame: Through study completion, on average 2 weeks. ]
    Adverse events will be tracked and recorded
  • Side effects [ Time Frame: Baseline and 16 hours post-stimulus for both arms of the crossover study. ]
    Side effects will be tracked with the Toronto Side Effects Questionnaire.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Cycloserine rTMS Plasticity Augmentation in Depression
Official Title  ICMJE A Randomized, Placebo-controlled, Crossover Trial of D-cycloserine Repetitive Transcranial Magnetic Stimulation Plasticity Enhancement in the Motor System of Individuals With Major Depressive Disorder.
Brief Summary Transcranial magnetic stimulation (rTMS) is an investigational and therapeutic modality that impacts the connection strength between neurons by delivering patterned energy. In response to this patterned energy neurons fire and adapt by changing their connection strengths. This change in connection strengths is believed to be the underlying mechanism whereby this intervention has therapeutic benefit for this intervention in conditions such as depression. The purpose of this study is to test a means of enhancing the effect of rTMS using a medication (cycloserine) that has been shown to augment and stabilize activity dependent neuronal changes. The investigators wish to use the motor system, where the associated muscle response to brain stimulation can be measured, to probe activity dependent changes in connection strength between neurons.
Detailed Description

This randomized, placebo-controlled, crossover trial will enroll 12 participants with Major Depressive Disorder. In one arm of the study, participants will randomly receive either 100mg of d-cycloserine (DCS, an antibiotic) or a placebo capsule, and participants will receive the other intervention one week later.

  1. We will recruit 12 participants aged 18-60 through community advertisement, carefully screened for exclusion factors related to rTMS and DCS.
  2. After screening, participants will come to the lab for a semi-structured interview involving the MINI-International Neuropsychiatric Interview for confirmation of the diagnosis of depression, and the absence of substance use disorders, absence of psychosis, and absence of bipolar disorder. The severity of their depressive symptoms will be quantified with the semi-structured clinical instrument Hamilton Depression Rating Scale, and participants will be retained in the study if their score is ≥15, indicating moderate severity. Finally, the antidepressant treatment history will be collected using the Antidepressant Treatment History Form.
  3. Eligible participants will be randomly assigned by random number sequence with allocation concealment to one of two first arms of the crossover study: a) placebo-DCS 100mg and b) DCS 100mg-placebo.
  4. Participants will complete the QIDS-SR (Quick Inventory of Depressive Symptoms-Self Report), the MDQ (Mood Disorders Questionnaire), the BAI (Beck Anxiety Inventory), and the STAI (State Trait Anxiety Inventory). Participants will report their perception of physical symptoms (potential side effects) in the 7 days before participating in the study taking the randomized capsule (Toronto Side Effects Scale - 1 Week).
  5. Participants will take their blinded capsule at least 30 minutes prior to TBS (we anticipate that it will take approximately 30 minutes to do steps 5-7).
  6. Electromyographic (EMG) electrodes will be positioned over the first dorsal interosseous (FDI) bilaterally. These are non-invasive electrodes that use an adhesive to stick to the skin.
  7. Using neuronavigation in conjunction with an atlas brain, the M1 hand strip will be localized using single pulse TMS (MagPro X100).
  8. Motor evoked potentials are measurements of muscle activation, in this case in response to TMS stimulation of the brain. We will use single pulse TMS to record the magnitude of responses. As a baseline, we will collect twenty single-pulse (120% resting motor threshold (RMT), 0.25Hz) MEPs every 5 minutes for the 15 minutes preceding TBS rTMS.
  9. We will characterize a stimulus response curve by delivering single pulse TMS at stimulation intensities ranging from 100-150% of resting motor threshold in random order.
  10. TBS rTMS will be applied to the FDI 'hotspot'. TBS consists of 2s trains every 10s. Trains are composed of 3 pulses at 50Hz, 200ms intervals, 80% RMT. Total time 190s and 600 pulses.
  11. After TBS, twenty MEPs will be acquired (single pulse, 120% RMT, 0.25Hz) every 5 minutes for the first 30 minutes, at 60 minutes, at 90 minutes, and at 16Hrs (the following morning).
  12. At the 90 minute and 16 Hrs timepoints, we will characterize stimulus response curves (MEPs at stimulus intensities ranging from 100-150% resting motor threshold presented in random order).
  13. Participants will report their perception of side effects since taking the randomized capsule (Toronto Side Effects Scale - 1 Day). Participants will be asked if they believe they received the study medication or placebo in this first phase of the crossover trial.

This study involves a crossover design, therefore after a minimum of 7 days, participants will return to the laboratory to repeat steps 4-13 with the other arm of the trial (i.e. participants who initially received the active study medication will instead receive the placebo, and the converse).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE Major Depressive Disorder
Intervention  ICMJE
  • Drug: Cycloserine
    Cycloserine 100mg
  • Device: Transcranial Magnetic Stimulation
    Single-pulse transcranial magnetic stimulation and theta-burst stimulation
  • Drug: Placebo Oral Tablet
    Placebo tablet matched to cycloserine tab
Study Arms  ICMJE
  • Experimental: D-Cycloserine
    Participants will ingest a capsule containing 100mg of the antibiotic d-cycloserine. Their baseline motor evoked potentials (MEP) will be recorded for 30 minutes prior to receiving theta-burst stimulation (TBS; a patterned stimulation) to the motor cortex and change in MEP amplitude will be measured following stimulation up to 90 minutes later and then once again the following morning (16 hours later).
    Interventions:
    • Drug: Cycloserine
    • Device: Transcranial Magnetic Stimulation
  • Active Comparator: Placebo
    Participants will ingest a capsule identical to the study medication, however this capsule will contain a placebo.Their baseline motor evoked potentials (MEP) will be recorded for 30 minutes prior to receiving theta-burst stimulation (TBS; a patterned stimulation) to the motor cortex and change in MEP amplitude will be measured following stimulation up to 90 minutes later and then once again the following morning (16 hours later).
    Interventions:
    • Device: Transcranial Magnetic Stimulation
    • Drug: Placebo Oral Tablet
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 27, 2018)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 1, 2020
Estimated Primary Completion Date September 3, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Individuals currently experiencing a major depressive episode. 1.1 As determined by the MINI-International Neuropsychiatric Interview 1.2 Moderate severity, as indicated by a Hamilton Depression Rating Scale score of ≥15.

    1.3 Be willing to remain on a stable medication regimen for 4 weeks prior the study and during the study

  2. Aged 18-60

Exclusion Criteria:

  1. Pregnancy
  2. Lactation
  3. Epilepsy
  4. Previous Stroke
  5. Current Renal Disease
  6. Current Liver Disease
  7. Current Alcohol Use Disorder
  8. Inability to refrain from alcohol use for 24 hours prior to each session and following each session.
  9. Allergy to antibiotics
  10. Use of isoniazid, ethionamide, or bupropion
  11. History of psychosis
  12. History of bipolar disorder
  13. Family history of bipolar disorder
  14. Intracranial metallic objects (dental hardware is not an exclusionary criteria)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alexander McGirr, MD MSc 403-210-6410 alexander.mcgirr@ucalgary.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03511599
Other Study ID Numbers  ICMJE REB18-0604
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: There will be no sharing of IPD.
Responsible Party University of Calgary
Study Sponsor  ICMJE University of Calgary
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University of Calgary
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP