Roflumilast and TMS Motor Plasticity

Conditions

• Other Conditions of Brain

Eligibility Criteria

Sex

ALL

Age

18 Years - 60 Years

Healthy Volunteers

Accepted

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.
• 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.
• 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.
• 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.

Study Details

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.

Key Dates

Start date

Nov 6, 2024

Status verified

Nov 2024

Primary completion

Aug 31, 2025

Completion

Jun 30, 2026

Study Design

Enrollment

20 participants (actual)

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Arms

• Placebo Comparator: Intermittent Theta-Burst Stimulation with Placebo
  Intermittent theta-burst stimulation delivered to the left primary motor cortex after the participant has ingested a placebo.
• Experimental: Intermittent Theta-Burst Stimulation with Roflumilast
  Intermittent theta-burst stimulation delivered to the left primary motor cortex after the participant has ingested roflumilast 500mcg.
• Placebo Comparator: Continuous Theta-Burst Stimulation with Placebo
  Continuous theta-burst stimulation delivered to the left primary motor cortex after the participant has ingested a placebo.
• Experimental: Continuous Theta-Burst Stimulation with Roflumilast
  Continuous theta-burst stimulation delivered to the left primary motor cortex after the participant has ingested roflumilast 500mcg.

Primary Outcome Measure

Motor evoked potential amplitude [ Time Frame: -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. ]