Other Conditions of BrainPhase 1NCT06457191
Roflumilast and TMS Motor Plasticity
A Phase 1 study testing Roflumilast, Intermittent theta-burst stimulation transcranial magnetic stimulation and Continuous theta-burst stimulation transcranial magnetic stimulation in people with Other Conditions of Brain, run by University of Calgary at 1 site in Canada.
Trial 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'. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Other Conditions of Brain
- What is being tested?
- Roflumilast, Intermittent theta-burst stimulation transcranial magnetic stimulation and Continuous theta-burst stimulation transcranial magnetic stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 6 Nov 2024to Jun 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy individuals (no chronic medical conditions).
- Aged 18-60 years.
Who cannot join
- Pregnancy
- Lactation
- Epilepsy
- Previous stroke
- Current Renal Disease
- Current Liver Disease
Show all 11Show fewer
- Allergy to roflumilast or any of its non-medicinal ingredients
- Current psychiatric concerns
- 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)
- Substance use disorder
- The inability to refrain from alcohol use for 24 hours prior to stimulation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: PDE4 Inhibition and Theta-burst Stimulation Transcranial Magnetic Stimulation Motor Plasticity: a Randomized Placebo-controlled Single-blind Crossover Study
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.
Read the detailed description
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
- Other Conditions of Brain
- Being tested
- Roflumilast, Placebo, Intermittent theta-burst stimulation transcranial magnetic stimulation, Continuous theta-burst stimulation transcranial magnetic stimulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RoflumilastDrug
Also called Active
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.
PlaceboDrug
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 stimulationDevice
Also called iTBS
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 stimulationDevice
Also called cTBS
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 group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Roflumilast; Device: Continuous theta-burst stimulation transcranial magnetic stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: -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
Motor evoked potentials will be measured using surface electrodes placed over the first dorsal interosseous muscle to varying stimulus intensities.
Measured: Baseline, 30 minutes following theta-burst stimulation, 60 minutes following theta-burst stimulation.
Cortical silent period
Motor evoked potentials will be measured using surface electrodes placed over the first dorsal interosseous muscle while participants maintain a light contracture of the muscle.
Measured: Baseline, 30 minutes following theta-burst stimulation, 60 minutes following theta-burst stimulation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2024
- Study start6 Nov 2024
- Primary completionAug 2025 (estimated)
- Study completionJun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Other Conditions of BrainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06457191
- Sponsor's protocol ID
- REB23-1506
- Status last verified
- Nov 2024
- First submitted
- 7 Jun 2024
- Last updated
- 3 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD will not be made available to other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PDE4 Inhibition and Theta-burst Stimulation Transcranial Magnetic Stimulation Motor Plasticity: a Randomized Placebo-controlled Single-blind Crossover Study
- ClinicalTrials.gov ID
- NCT06457191
- Acronym / sponsor ID
- REB23-1506
- Conditions
- Other Conditions of Brain
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Study start
- 6 Nov 2024 (actual)
- Primary completion
- Aug 2025 (estimated)
- Study completion
- Jun 2026 (estimated)
- First posted
- 13 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Intermittent Theta-Burst Stimulation with Placebo | Placebo comparator | Drug: Placebo, Device: Intermittent theta-burst stimulation transcranial magnetic stimulationIntermittent theta-burst stimulation delivered to the left primary motor cortex after the participant has ingested a placebo. |
| Intermittent Theta-Burst Stimulation with Roflumilast | Experimental | Drug: Roflumilast, Device: Intermittent theta-burst stimulation transcranial magnetic stimulationIntermittent theta-burst stimulation delivered to the left primary motor cortex after the participant has ingested roflumilast 500mcg. |
| Continuous Theta-Burst Stimulation with Placebo | Placebo comparator | Drug: Placebo, Device: Continuous theta-burst stimulation transcranial magnetic stimulationContinuous theta-burst stimulation delivered to the left primary motor cortex after the participant has ingested a placebo. |
| Continuous Theta-Burst Stimulation with Roflumilast | Experimental | Drug: Roflumilast, Device: Continuous theta-burst stimulation transcranial magnetic stimulationContinuous theta-burst stimulation delivered to the left primary motor cortex after the participant has ingested roflumilast 500mcg. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy individuals (no chronic medical conditions).
- Aged 18-60 years.
Key exclusion criteria (11 listed)
- Pregnancy
- Lactation
- Epilepsy
- Previous stroke
- Current Renal Disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RoflumilastAlso: ActiveParticipants will ingest either a placebo or roflumilast 500mg in a single blind crossover study and receive transcranial magnetic stimulation to the primary motor cortex. | Drug | Continuous Theta-Burst Stimulation with Roflumilast, Intermittent Theta-Burst Stimulation with Roflumilast |
| PlaceboParticipants will ingest either a placebo or roflumilast 500mg in a single blind crossover study and receive transcranial magnetic stimulation to the primary motor cortex. | Drug | Continuous Theta-Burst Stimulation with Placebo, Intermittent Theta-Burst Stimulation with Placebo |
| Intermittent theta-burst stimulation transcranial magnetic stimulationAlso: iTBSIntermittent 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. | Device | Intermittent Theta-Burst Stimulation with Placebo, Intermittent Theta-Burst Stimulation with Roflumilast |
| Continuous theta-burst stimulation transcranial magnetic stimulationAlso: cTBSContinuous 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. | Device | Continuous Theta-Burst Stimulation with Placebo, Continuous Theta-Burst Stimulation with Roflumilast |
Primary outcome
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.
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.
2 secondary outcomes
Motor evoked potential stimulus response curve
Time frame: Baseline, 30 minutes following theta-burst stimulation, 60 minutes following theta-burst stimulation.
Cortical silent period
Time frame: Baseline, 30 minutes following theta-burst stimulation, 60 minutes following theta-burst stimulation.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2025.
- Individual participant dataSharing planned: No. IPD will not be made available to other researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Roflumilast, Intermittent theta-burst stimulation transcranial magnetic stimulation and Continuous theta-burst stimulation transcranial magnetic stimulation in people with Other Conditions of Brain, run by University of Calgary at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 3 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2025.