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Completed

NCT Number: NCT03432689

Cycloserine rTMS Plasticity Augmentation

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.

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Key information

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

University of Calgary

Calgary, Alberta, T2N1N4, Canada

About this study

This randomized, placebo-controlled, crossover trial will enroll 12 healthy participants. 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.

  • The investigators will recruit 12 healthy participants through community advertisement, carefully screened for exclusion factors related to rTMS and DCS.
  • 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.
  • 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 take their blinded capsule at least 30 minutes hours prior to TBS. (we anticipate that it will take approximately 30 minutes to do steps 5-7).
  • Electromyographic (EMG) electrodes will be positioned over the first dorsal interosseous (FDI) bilaterally to record motor evoked potentials (MEPs). These are non-invasive electrodes that use an adhesive to stick to the skin.
  • Using neuronavigation in conjunction with an atlas brain, the M1 hand strip will be localized using single pulse TMS (MagPro X100).
  • Motor evoked potentials are measurements of muscle activation, in this case in response to TMS stimulation of the brain. The investigators will use single pulse TMS to record the magnitude of responses. As a baseline, the investigators will collect twenty single-pulse (120% resting motor threshold (RMT), 0.25Hz) MEPs every 5 minutes for the 15 minutes preceding TBS rTMS.
  • 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.
  • 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).
  • At the 16 Hrs time point, the investigators will characterize stimulus response curves (MEPs at stimulus intensities ranging from 100-150% resting motor threshold presented in random order).

As this is a cross-over study, participants will return 1 week later to repeat the second arm of the protocol and will repeat steps 2-10).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Healthy individuals 18-60 years of age.

Exclusion criteria

  • Pregnancy
  • Lactation
  • Epilepsy
  • Previous Stroke
  • Current Renal Disease
  • Current Liver Disease
  • Current Alcohol Use Disorder
  • Inability to refrain from alcohol use for 24 hours prior to each session and following each session.
  • Allergy to antibiotics
  • Use of isoniazid, ethionamide or bupropion
  • Current psychiatric concerns
  • History of bipolar disorder
  • Family history of bipolar disorder
  • Intracranial implants (dental implants are not an exclusion criteria)

Treatment and study plan

Transcranial Magnetic Stimulation

Device

Single-pulse transcranial magnetic stimulation and theta-burst stimulation

Cycloserine

Drug

Cycloserine 100mg

Placebo oral tablet

Drug

Placebo capsule matched to cycloserine capsule

Primary outcomes

  1. 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.

Secondary outcomes

  1. Motor Evoked Potential dose-response curve

    Time frame: Baseline versus 90 minutes following theta-burst stimulation.

    Motor Evoked Potentials at stimulus intensities ranging from 100-150% resting motor threshold, presented in random order.

  2. 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 in random order.

  3. Motor Evoked Potential Amplitude Time Course

    Time frame: 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.

Other outcomes

  1. Safety outcomes

    Time frame: Through study completion, on average 2 weeks.

    Adverse events will be tracked and recorded

  2. Side effects

    Time frame: Pre-stimulus and 16 hours post-stimulus for both arms of the crossover study.

    Side effects will be tracked with the Toronto Side Effects Questionnaire

Sponsors and collaborators

Lead sponsor

University of Calgary

Other

Registry information

Official study title

A Randomized, Placebo-controlled, Crossover Trial of Cycloserine Repetitive Transcranial Magnetic Stimulation Plasticity Enhancement in the Healthy Motor System.

Important dates

Study start
2018
Primary completion
2018
Study completion
2018
First posted
Feb 14, 2018
Registry last updated
Nov 9, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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