Roflumilast and TMS Motor Plasticity

NCT ID: NCT06457191

Last Updated: 2025-07-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-06

Study Completion Date

2026-06-30

Brief Summary

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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.

Detailed Description

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This study will employ a randomized, placebo-controlled single-blind crossover trial of adjunctive roflumilast with intermittent or continuous theta burst (iTBS/cTBS) TMS to the primary motor cortex. Participants will complete a screen visit to determine eligibility based on the inclusion/exclusion criteria. If the participants are not eligible, no further study procedures will be conducted.

Randomization with allocation concealment of eligible patients to begin with either the study medication or placebo arm of the study will involve a random number sequence generated a priori with atmospheric noise, with single-blind random condition assignment and allocation concealment.

Baseline corticospinal excitability will be quantified. One hour following ingestion of the blinded capsule iTBS/cTBS will be applied to the primary motor cortex, and the response will be quantified through a combination of motor evoked potentials (MEPs) at a fixed stimulus intensity, cortical silent period, and a range of stimuli to generate stimulus response curves (SRCs).

The duration of each arm is up to 2.5 hours, and they will be separated by at least 1 week.

All participants will complete a questionnaire to assess any side effects (emotional and physical) following each rTMS session.

Conditions

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Other Conditions of Brain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Investigators Outcome Assessors

Study Groups

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Intermittent Theta-Burst Stimulation with Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type 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

Intervention Type 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.

Intermittent Theta-Burst Stimulation with Roflumilast

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

Group Type EXPERIMENTAL

Roflumilast

Intervention Type 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

Intervention Type 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 with Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type 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 transcranial magnetic stimulation

Intervention Type 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.

Continuous Theta-Burst Stimulation with Roflumilast

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

Group Type EXPERIMENTAL

Roflumilast

Intervention Type 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 transcranial magnetic stimulation

Intervention Type 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.

Interventions

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Roflumilast

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.

Intervention Type DRUG

Placebo

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.

Intervention Type DRUG

Intermittent theta-burst stimulation transcranial magnetic stimulation

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.

Intervention Type DEVICE

Continuous theta-burst stimulation transcranial magnetic stimulation

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.

Intervention Type DEVICE

Other Intervention Names

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Active iTBS cTBS

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

1. Pregnancy
2. Lactation
3. Epilepsy
4. Previous stroke
5. Current Renal Disease
6. Current Liver Disease
7. Allergy to roflumilast or any of its non-medicinal ingredients
8. Current psychiatric concerns
9. Currently taking any medications with known serious interactions with roflumilast (abametapir, apalutamide, dabrafenifb, enzalutamide, fexinidazole, idelalisib, ivosidenib, lonadarnib, ritonavir, secobarbital, tucatinib, and voxelotor).Intracranial metallic objects (dental hardware is not an exclusionary criterion)
10. Substance use disorder
11. The inability to refrain from alcohol use for 24 hours prior to stimulation
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Calgary

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Calgary

Calgary, Alberta, Canada

Site Status

Countries

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Canada

Other Identifiers

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REB23-1506

Identifier Type: -

Identifier Source: org_study_id

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