Roflumilast TMS-EEG Plasticity

NCT04369547 | Withdrawn Phase 1

• 1 other identifier: REB20-0196
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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'. 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.

Conditions

Synaptic Plasticity

Keywords

rTMS; EEG; Augmented Plasticity

Outcome Measures

Primary Outcomes (1)

• TMS Evoked Potential amplitude

  Change in the electrical response of neurons in the dorsolateral prefrontal cortex will be recorded.

  Baseline versus 10, 20, and 30 minutes following theta-burst stimulation.

Study Arms (2)

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.

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.

Device: Transcranial Magnetic Stimulation; Drug: Placebo oral tablet

Interventions

Transcranial Magnetic Stimulation DEVICE

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

Placebo; Roflumilast

Roflumilast DRUG

Roflumilast 250mcg

Roflumilast

Placebo oral tablet DRUG

Placebo capsule matched to roflumilast capsule

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• Pregnancy
• Lactation
• Epilepsy
• Previous stroke
• Current Renal Disease
• Current Liver Disease
• Allergy to roflumilast or any of its non-medicinal ingredients
• Current psychiatric concerns
• Currently taking any medications that interact with roflumilast
• Substance use disorder
• The inability to refrain from alcohol use for 24 hours prior to stimulation

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

University of Calgary

Calgary, Alberta, T2N1N4, Canada

Location

MeSH Terms

Interventions

Transcranial Magnetic Stimulation; Roflumilast

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Alexander McGirr, MD PhD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 27, 2020
• First Posted: April 30, 2020
• Study Start: January 1, 2022
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: December 28, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)