MedDataX Logo

Roflumilast TMS-EEG Plasticity

NCT ID: NCT04369547

Last Updated: 2021-12-28

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

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2022-01-31

Study Completion Date

2023-09-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

1. The investigators will recruit 20 healthy participants through community advertisement, carefully screened for exclusion factors related to rTMS and roflumilast.
2. 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.
3. 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).
4. Participants will take their blinded capsule at least 30 minutes prior to TBS (theta-burst stimulation).
5. 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.
6. The M1 hand strip will be localized using single pulse TMS (MagPro X100) in conjunction with neuronavigation and an atlas brain.
7. 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.
8. 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.
9. 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.
10. 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

See the medical conditions and disease areas that this research is targeting or investigating.

Synaptic Plasticity

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

rTMS EEG Augmented Plasticity

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Roflumilast

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.

Group Type EXPERIMENTAL

Transcranial Magnetic Stimulation

Intervention Type DEVICE

Single-pulse transcranial magnetic stimulation and theta-burst stimulation.

Roflumilast

Intervention Type DRUG

Roflumilast 250mcg

Placebo

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.

Group Type PLACEBO_COMPARATOR

Transcranial Magnetic Stimulation

Intervention Type DEVICE

Single-pulse transcranial magnetic stimulation and theta-burst stimulation.

Placebo oral tablet

Intervention Type DRUG

Placebo capsule matched to roflumilast capsule

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Transcranial Magnetic Stimulation

Single-pulse transcranial magnetic stimulation and theta-burst stimulation.

Intervention Type DEVICE

Roflumilast

Roflumilast 250mcg

Intervention Type DRUG

Placebo oral tablet

Placebo capsule matched to roflumilast capsule

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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 that interact with roflumilast
10. Intracranial metallic objects (dental hardware is not an exclusionary criterion)
11. Substance use disorder
12. 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

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Calgary

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Alexander McGirr

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Alexander McGirr, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University of Calgary

Calgary, Alberta, Canada

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Canada

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

REB20-0196

Identifier Type: -

Identifier Source: org_study_id