Cycloserine rTMS Plasticity Augmentation

NCT ID: NCT03432689

Last Updated: 2018-11-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-06
• Study Completion Date: 2018-11-07

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 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.

1. The investigators will recruit 12 healthy participants through community advertisement, carefully screened for exclusion factors related to rTMS and DCS.

2. 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.

3. 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).

4. 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).

5. 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.

6. Using neuronavigation in conjunction with an atlas brain, the M1 hand strip will be localized using single pulse TMS (MagPro X100).

7. 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.

8. 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.

9. 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).

10. 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).

Conditions

Motor Activity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: EXPERIMENTAL

Transcranial Magnetic Stimulation

Intervention Type: DEVICE

Single-pulse transcranial magnetic stimulation and theta-burst stimulation

Cycloserine

Intervention Type: DRUG

Cycloserine 100mg

Placebo

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).

Group Type: PLACEBO_COMPARATOR

Transcranial Magnetic Stimulation

Intervention Type: DEVICE

Single-pulse transcranial magnetic stimulation and theta-burst stimulation

Placebo Oral Tablet

Intervention Type: DRUG

Placebo capsule matched to cycloserine capsule

Interventions

Transcranial Magnetic Stimulation

Single-pulse transcranial magnetic stimulation and theta-burst stimulation

Intervention Type: DEVICE

Cycloserine

Cycloserine 100mg

Intervention Type: DRUG

Placebo Oral Tablet

Placebo capsule matched to cycloserine capsule

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Healthy individuals 18-60 years of age.

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. Current psychiatric concerns

12. History of bipolar disorder

13. Family history of bipolar disorder

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Calgary

OTHER

Sponsor Role: lead

Responsible Party

Alexander McGirr

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alexander McGirr, MD MSc

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Locations

University of Calgary

Calgary, Alberta, Canada

Countries

Canada

Other Identifiers

REB17-2314

Identifier Type: -

Identifier Source: org_study_id