Cycloserine rTMS Plasticity Augmentation in Depression

NCT03511599 | Completed Phase 1 FDA Drug FDA Device

• 1 other identifier: REB18-0604
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (3)

• Motor evoked potential dose-response curve

  Baseline versus 90 minutes after theta-burst stimulation.

• Motor evoked potential dose-response curve

  Baseline versus 16 hours following theta-burst stimulation.

• Motor evoked potential amplitude

  Baseline and the evolution over 90 minutes following theta-burst stimulation.

Other Outcomes (2)

• Safety outcomes

  Through study completion, on average 2 weeks.

• Side effects

  Baseline and 16 hours post-stimulus for both arms of the crossover study.

Study Arms (2)

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).

Drug: Cycloserine; Device: Transcranial Magnetic Stimulation

Placebo

ACTIVE COMPARATOR

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).

Device: Transcranial Magnetic Stimulation; Drug: Placebo Oral Tablet

Interventions

Cycloserine DRUG

Cycloserine 100mg

D-Cycloserine

Transcranial Magnetic Stimulation DEVICE

Single-pulse transcranial magnetic stimulation and theta-burst stimulation

D-Cycloserine; Placebo

Placebo Oral Tablet DRUG

Placebo tablet matched to cycloserine tab

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Be willing to remain on a stable medication regimen for 4 weeks prior the study and during the study
• Aged 18-60

You may not qualify if:

• 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
• History of psychosis
• History of bipolar disorder
• Family history of bipolar disorder

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

University of Calgary

Calgary, Alberta, T2N1N4, Canada

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Cycloserine; Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oxazolidinones; Oxazoles; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins; Magnetic Field Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2018
• First Posted: April 30, 2018
• Study Start: September 3, 2018
• Primary Completion: December 8, 2020
• Study Completion: April 21, 2021
• Last Updated: January 5, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share

Locations

CA (1)