Roflumilast and TMS Motor Plasticity

NCT06457191 | Active Not Recruiting Phase 1

• 1 other identifier: REB23-1506
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Repetitive transcranial magnetic stimulation (rTMS) uses a magnetic field to non-invasively induce electrical function within the brain. Stimulation allows brain cells to change the way that they adapt and communicate with each other, known as 'synaptic plasticity'. It is thought that alterations in these adaptive brain changes underlie the ability of rTMS to treat mental illnesses like depression. The regulation of synaptic plasticity is complex, and involves multiple interacting factors and redundant systems to ensure that plasticity is carefully regulated. To date, studies attempting to alter impact synaptic plasticity have done so using pharmacological adjuncts that target extracellular contributions to plasticity. Here, we propose the first proof of principle study targeting intracellular regulation of plasticity by using a pharmacological adjunct targeting Phosphodiesterase 4 (PDE4), a key regulator a cyclic AMP gradients in brain cells. We will pair TMS with electromyography (EMG) to measure activity dependent changes in the motor cortex following rTMS to test the ability of a PDE4 inhibition to enhance synaptic plasticity after rTMS.

Conditions

Other Conditions of Brain

Outcome Measures

Primary Outcomes (1)

• Motor evoked potential amplitude

  Motor evoked potentials will be measured using surface electrodes placed over the first dorsal interosseous muscle of the hand to a single stimulus intensity of 120% of resting motor threshold.

  -5 minutes, -10minutes, -5 minutes, and immediately prior to theta-burst stimulation, then +5 minutes, +10 minutes, +15 minutes, +20 minutes, +25 minutes, +30 minutes, +45 minutes and +60 minutes after theta-burst stimulation.

Secondary Outcomes (2)

• Motor evoked potential stimulus response curve

  Baseline, 30 minutes following theta-burst stimulation, 60 minutes following theta-burst stimulation.

• Cortical silent period

  Baseline, 30 minutes following theta-burst stimulation, 60 minutes following theta-burst stimulation.

Study Arms (4)

Intermittent Theta-Burst Stimulation with Placebo

PLACEBO COMPARATOR

Intermittent theta-burst stimulation delivered to the left primary motor cortex after the participant has ingested a placebo.

Drug: Placebo; Device: Intermittent theta-burst stimulation transcranial magnetic stimulation

Intermittent Theta-Burst Stimulation with Roflumilast

EXPERIMENTAL

Intermittent theta-burst stimulation delivered to the left primary motor cortex after the participant has ingested roflumilast 500mcg.

Drug: Roflumilast; Device: Intermittent theta-burst stimulation transcranial magnetic stimulation

Continuous Theta-Burst Stimulation with Placebo

PLACEBO COMPARATOR

Continuous theta-burst stimulation delivered to the left primary motor cortex after the participant has ingested a placebo.

Drug: Placebo; Device: Continuous theta-burst stimulation transcranial magnetic stimulation

Continuous Theta-Burst Stimulation with Roflumilast

EXPERIMENTAL

Continuous theta-burst stimulation delivered to the left primary motor cortex after the participant has ingested roflumilast 500mcg.

Drug: Roflumilast; Device: Continuous theta-burst stimulation transcranial magnetic stimulation

Interventions

Roflumilast DRUG

Participants will ingest either a placebo or roflumilast 500mg in a single blind crossover study and receive transcranial magnetic stimulation to the primary motor cortex.

Also known as: Active

Continuous Theta-Burst Stimulation with Roflumilast; Intermittent Theta-Burst Stimulation with Roflumilast

Placebo DRUG

Participants will ingest either a placebo or roflumilast 500mg in a single blind crossover study and receive transcranial magnetic stimulation to the primary motor cortex.

Continuous Theta-Burst Stimulation with Placebo; Intermittent Theta-Burst Stimulation with Placebo

Intermittent theta-burst stimulation transcranial magnetic stimulation DEVICE

Intermittent theta-burst stimulation consists of 2 second trains every 10 seconds. Each train is composed of 3 pulses at 50Hz, 200 milliseconds intervals given at 80% resting motor threshold. The total time for this treatment stimulus is 600 pulses over 190 seconds.

Also known as: iTBS

Intermittent Theta-Burst Stimulation with Placebo; Intermittent Theta-Burst Stimulation with Roflumilast

Continuous theta-burst stimulation transcranial magnetic stimulation DEVICE

Continuous theta-burst stimulation consists of 2 second trains every 10 seconds. Each train is composed of 3 pulses at 50Hz, 200 milliseconds intervals given at 80% resting motor threshold. The total time for this treatment stimulus is 600 pulses over 40 seconds.

Also known as: cTBS

Continuous Theta-Burst Stimulation with Placebo; Continuous Theta-Burst Stimulation with Roflumilast

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy individuals (no chronic medical conditions).
• Aged 18-60 years.

You may not qualify if:

• Pregnancy
• Lactation
• Epilepsy
• Previous stroke
• Current Renal Disease
• Current Liver Disease
• Allergy to roflumilast or any of its non-medicinal ingredients
• Current psychiatric concerns
• Substance use disorder
• The inability to refrain from alcohol use for 24 hours prior to stimulation

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

University of Calgary

Calgary, Alberta, T2N 1N4, Canada

Location

MeSH Terms

Interventions

Roflumilast; Exercise

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Design

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

Study Record Dates

• First Submitted: June 7, 2024
• First Posted: June 13, 2024
• Study Start: November 6, 2024
• Primary Completion: August 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: July 3, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)