Synaptic PlasticityPhase 1NCT04369547
Roflumilast TMS-EEG Plasticity
A Phase 1 study testing Transcranial Magnetic Stimulation and Roflumilast in people with Synaptic Plasticity, 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
- Synaptic Plasticity
- What is being tested?
- Transcranial Magnetic Stimulation and Roflumilast
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2022to 1 Sep 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 12Show fewer
- Allergy to roflumilast or any of its non-medicinal ingredients
- Current psychiatric concerns
- Currently taking any medications that interact with roflumilast
- 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: A Double-blind Placebo-controlled Crossover Study of Roflumilast Synaptic Plasticity Enhancement: a TMS-EEG 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. rTMS is a Health Canada approved treatment for depression, however, 2/3rds of people fail to show meaningful improvement. This highlights the need for more effective therapeutic means. The purpose of the present study is to augment the therapeutic abilities of rTMS through the conjunctive use of a medication that also increases synaptic plasticity. We will pair TMS with an electroencephalograph (EEG) to measure activity dependent changes in the frontal cortex following rTMS.
Read the detailed description
This randomized, placebo-controlled, crossover trial will enroll 20 healthy participants. In one arm of the study, participants will randomly receive either 250mcg of roflumilast (a phosphodiesterase-4 inhibitor), or a placebo capsule, and participants will receive the other intervention one week later.
- The investigators will recruit 20 healthy participants through community advertisement, carefully screened for exclusion factors related to rTMS and roflumilast.
- Participants will be randomly assigned by random number sequence with allocation concealment to one of two first arms of the crossover study: a) placebo-roflumilast 250mcg and b) roflumilast 250mcg-placebo.
- Participants will complete the QIDS-SR (Quick Inventory of Depressive Symptoms-Self Report), the BAI (Beck Anxiety Inventory), and the STAI (State Trait Anxiety Inventory). Participants will report their perception of physical symptoms (potential side effects) in the 7 days before participating in the study taking the randomized capsule (Toronto Side Effects Scale - 1 Week).
- Participants will take their blinded capsule at least 30 minutes prior to TBS (theta-burst stimulation).
- The resting motor threshold of participants will be determined using electromyographic electrodes (EMG). EMG electrodes will be positioned over the first dorsal interosseous (FDI) muscle on the right hand. These electrodes are non-invasive and use an adhesive to stick to the skin.
- The M1 hand strip will be localized using single pulse TMS (MagPro X100) in conjunction with neuronavigation and an atlas brain.
- Muscle activation in response to TMS will be measured through motor evoked potentials (MEP). The strength of MEPs in response to differing strengths of single pulse TMS will be used to determine a participants resting motor threshold (RMT). The RMT is the lowest TMS setting at which the FDI muscle responds to TMS stimulus. 80% of the RMT will then be the strength at which TBS protocol will be applied to the DLPFC.
- Two baselines of TMS Evoked Potentials (TEPs) will be collected via one hundred single-pulse (120% RMT), 0.25Hz) over the F3 site. Each baseline will occur 10 minutes apart.
- TBS-rTMS will be applied to the DLPFC site. TBS consists of 2s trains every 10s. Each train is composed of 3 pulses at 50Hz, 200ms intervals given at 80% RMT. The total time for this treatment stimulus is 600 pulses over 190s.
- Following TBS, one hundred TEPs over the F3 site will again be acquired at 10, 20, and 30 minutes after treatment (single pulse, 120%RMT, 0.25Hz).
As this is a cross-over study, participants will return 1 week later to repeat the second arm of the protocol (steps 3-10).
- Conditions
- Synaptic Plasticity
- Being tested
- Transcranial Magnetic Stimulation, Roflumilast, Placebo oral tablet
- Keywords
- rTMS, EEG, Augmented Plasticity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic StimulationDevice
Single-pulse transcranial magnetic stimulation and theta-burst stimulation.
RoflumilastDrug
Roflumilast 250mcg
Placebo oral tabletDrug
Placebo capsule matched to roflumilast capsule
| Study group | Role | What they receive |
|---|---|---|
| Roflumilast | Experimental | Participants will ingest a capsule containing 250mcg of the phosphodiesterase-4 inhibitor roflumilast. Their baseline TMS evoked potentials (TEP) will be recorded over 100 single TMS pulses prior to receiving theta-burst stimulation (TBS; a patterned stimulation) to the left dorsolateral prefrontal cortex (DLPFC). TEP will then be re-recorded at 10, 20, and 30 minutes post-stimulation. Receives: Device: Transcranial Magnetic Stimulation; Drug: Roflumilast |
| Placebo | Placebo comparator | Participants will ingest a capsule identical to that containing the study medication, however, this capsule will be contain a placebo. Their baseline TEP will be recorded over 100 single TMS pulses prior to receiving TBS to the left DLPFC. TEP will then be re-recorded at 10, 20, and 30 minutes post-stimulation. Receives: Device: Transcranial Magnetic Stimulation; Drug: Placebo oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
TMS Evoked Potential amplitude
Change in the electrical response of neurons in the dorsolateral prefrontal cortex will be recorded.
Measured: Baseline versus 10, 20, and 30 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 posted30 Apr 2020
- Study startJan 2022 (estimated)
- Primary completion1 Sep 2023 (estimated)
- Study completion1 Sep 2023 (estimated)
Why it stopped: Resource limitations
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Synaptic PlasticityStudies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alexander McGirr, University of Calgary
- Investigators
- Alexander McGirr, MD PhD, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04369547
- Sponsor's protocol ID
- REB20-0196
- Status last verified
- Dec 2021
- First submitted
- 27 Apr 2020
- Last updated
- 28 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There will be no sharing of individual participant data.
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind Placebo-controlled Crossover Study of Roflumilast Synaptic Plasticity Enhancement: a TMS-EEG Study
- ClinicalTrials.gov ID
- NCT04369547
- Acronym / sponsor ID
- REB20-0196
- Conditions
- Synaptic Plasticity
- Keywords
- rTMS, EEG, Augmented Plasticity
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Resource limitations
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Study start
- Jan 2022 (estimated)
- Primary completion
- 1 Sep 2023 (estimated)
- Study completion
- 1 Sep 2023 (estimated)
- First posted
- 30 Apr 2020 (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. rTMS is a Health Canada approved treatment for depression, however, 2/3rds of people fail to show meaningful improvement. This highlights the need for more effective therapeutic means. The purpose of the present study is to augment the therapeutic abilities of rTMS through the conjunctive use of a medication that also increases synaptic plasticity. We will pair TMS with an electroencephalograph (EEG) to measure activity dependent changes in the frontal cortex following rTMS.
Detailed description
This randomized, placebo-controlled, crossover trial will enroll 20 healthy participants. In one arm of the study, participants will randomly receive either 250mcg of roflumilast (a phosphodiesterase-4 inhibitor), or a placebo capsule, and participants will receive the other intervention one week later.
- The investigators will recruit 20 healthy participants through community advertisement, carefully screened for exclusion factors related to rTMS and roflumilast.
- Participants will be randomly assigned by random number sequence with allocation concealment to one of two first arms of the crossover study: a) placebo-roflumilast 250mcg and b) roflumilast 250mcg-placebo.
- Participants will complete the QIDS-SR (Quick Inventory of Depressive Symptoms-Self Report), the BAI (Beck Anxiety Inventory), and the STAI (State Trait Anxiety Inventory). Participants will report their perception of physical symptoms (potential side effects) in the 7 days before participating in the study taking the randomized capsule (Toronto Side Effects Scale - 1 Week).
- Participants will take their blinded capsule at least 30 minutes prior to TBS (theta-burst stimulation).
- The resting motor threshold of participants will be determined using electromyographic electrodes (EMG). EMG electrodes will be positioned over the first dorsal interosseous (FDI) muscle on the right hand. These electrodes are non-invasive and use an adhesive to stick to the skin.
- The M1 hand strip will be localized using single pulse TMS (MagPro X100) in conjunction with neuronavigation and an atlas brain.
- Muscle activation in response to TMS will be measured through motor evoked potentials (MEP). The strength of MEPs in response to differing strengths of single pulse TMS will be used to determine a participants resting motor threshold (RMT). The RMT is the lowest TMS setting at which the FDI muscle responds to TMS stimulus. 80% of the RMT will then be the strength at which TBS protocol will be applied to the DLPFC.
- Two baselines of TMS Evoked Potentials (TEPs) will be collected via one hundred single-pulse (120% RMT), 0.25Hz) over the F3 site. Each baseline will occur 10 minutes apart.
- TBS-rTMS will be applied to the DLPFC site. TBS consists of 2s trains every 10s. Each train is composed of 3 pulses at 50Hz, 200ms intervals given at 80% RMT. The total time for this treatment stimulus is 600 pulses over 190s.
- Following TBS, one hundred TEPs over the F3 site will again be acquired at 10, 20, and 30 minutes after treatment (single pulse, 120%RMT, 0.25Hz).
As this is a cross-over study, participants will return 1 week later to repeat the second arm of the protocol (steps 3-10).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Roflumilast | Experimental | Device: Transcranial Magnetic Stimulation, Drug: RoflumilastParticipants will ingest a capsule containing 250mcg of the phosphodiesterase-4 inhibitor roflumilast. Their baseline TMS evoked potentials (TEP) will be recorded over 100 single TMS pulses prior to receiving theta-burst stimulation (TBS; a patterned stimulation) to the left dorsolateral prefrontal cortex (DLPFC). TEP will then be re-recorded at 10, 20, and 30 minutes post-stimulation. |
| Placebo | Placebo comparator | Device: Transcranial Magnetic Stimulation, Drug: Placebo oral tabletParticipants will ingest a capsule identical to that containing the study medication, however, this capsule will be contain a placebo. Their baseline TEP will be recorded over 100 single TMS pulses prior to receiving TBS to the left DLPFC. TEP will then be re-recorded at 10, 20, and 30 minutes post-stimulation. |
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 (12 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 |
|---|---|---|
| Transcranial Magnetic StimulationSingle-pulse transcranial magnetic stimulation and theta-burst stimulation. | Device | Placebo, Roflumilast |
| RoflumilastRoflumilast 250mcg | Drug | Roflumilast |
| Placebo oral tabletPlacebo capsule matched to roflumilast capsule | Drug | Placebo |
Primary outcome
TMS Evoked Potential amplitude
Time frame: Baseline versus 10, 20, and 30 minutes following theta-burst stimulation.
Change in the electrical response of neurons in the dorsolateral prefrontal cortex will be recorded.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2021.
- Individual participant dataSharing planned: No. There will be no sharing of individual participant data.
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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.
Alexander McGirr, MD PhD principal investigator
University of Calgary
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 Transcranial Magnetic Stimulation and Roflumilast in people with Synaptic Plasticity, 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 12 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: withdrawn, as of the sponsor's last update on 28 Dec 2021. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
TMS Evoked Potential amplitude (time frame: Baseline versus 10, 20, and 30 minutes following 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 28 Dec 2021.