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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.
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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| D-Cycloserine | Experimental | 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). |
|
| Placebo | Placebo Comparator | Participants will ingest a capsule identical to that containing 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Transcranial Magnetic Stimulation | Device | Single-pulse transcranial magnetic stimulation and theta-burst stimulation |
|
| Measure | Description | Time Frame |
|---|---|---|
| Motor Evoked Potential amplitude | 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. | Baseline versus 90 minutes following theta-burst stimulation. |
| Measure | Description | Time Frame |
|---|---|---|
| Motor Evoked Potential dose-response curve | Motor Evoked Potentials at stimulus intensities ranging from 100-150% resting motor threshold, presented in random order. | Baseline versus 90 minutes following theta-burst stimulation. |
| Motor Evoked Potential dose-response curve |
| Measure | Description | Time Frame |
|---|---|---|
| Safety outcomes | Adverse events will be tracked and recorded | Through study completion, on average 2 weeks. |
| Side effects | Side effects will be tracked with the Toronto Side Effects Questionnaire |
Inclusion Criteria:
1. Healthy individuals 18-60 years of age.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alexander McGirr, MD MSc | University of Calgary | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Calgary | Calgary | Alberta | T2N1N4 | Canada |
There will be no sharing of individual participant data.
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| ID | Term |
|---|---|
| D009043 | Motor Activity |
| ID | Term |
|---|---|
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D050781 | Transcranial Magnetic Stimulation |
| D003523 | Cycloserine |
| ID | Term |
|---|---|
| D055909 | Magnetic Field Therapy |
| D013812 | Therapeutics |
| D007555 | Isoxazoles |
| D001393 | Azoles |
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| Cycloserine | Drug | Cycloserine 100mg |
|
| Placebo Oral Tablet | Drug | Placebo capsule matched to cycloserine capsule |
|
Motor Evoked Potentials at stimulus intensities ranging from 100-150% resting motor threshold, presented in random order. |
| Baseline versus 16 hours following theta-burst stimulation. |
| Motor Evoked Potential Amplitude Time Course | 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. | 90 minutes following theta-burst stimulation. |
| Pre-stimulus and 16 hours post-stimulus for both arms of the crossover study. |
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D023303 | Oxazolidinones |
| D010080 | Oxazoles |
| D012694 | Serine |
| D021542 | Amino Acids, Neutral |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |