Transcranial Magnetic Stimulation in Nonfluent/Agrammatic Variant Primary Progressive Aphasia

NCT ID: NCT03153540

Last Updated: 2022-03-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-01
• Study Completion Date: 2022-02-14

Brief Summary

Nonfluent/agrammatic variant primary progressive aphasia (nf/avPPA) is a fatal neurodegenerative disease that begins with isolated language deficits. There is currently no cure or treatment for this disease. Repetitive Transcranial Magnetic Stimulation (rTMS), a noninvasive neuromodulatory technique, is effective in major depression, and studied in many other conditions including nf/avPPA. Here the investigators propose to study the feasibility and change in language and brain function of a newer rTMS protocol (intermittent theta-burst stimulation, iTBS) using a randomized, blinded crossover design: participants will receive active or sham iTBS for two weeks and then switch groups without them or clinicians knowing their group. The investigators hypothesize that brain function and performance with language tasks will change after active iTBS.

Detailed Description

This study is a randomized controlled blinded cross-over treatment trial that involves 20 iTBS treatment sessions (10 active treatment sessions; 10 sham treatment sessions) and the study will last between 6 weeks. There will be 20 treatment visits (Monday-Friday) each lasting 10-40 minutes. Whether the participant is randomly assigned to active or sham treatment, the participant will receive daily 10 minute session of iTBS treatment. Some sessions will include behavioral and neurophysiological measures.

In addition, participants will complete cognitive testing, and neuro-imaging, including functional magnetic resonance (fMRI), functional near infrared spectroscopy (fNIRS) and electroencephalography (EEG) prior to the commencement of iTBS/sham treatment and at post-treatment. Safety and tolerability will be evaluated during daily iTBS treatments.

After 10 iTBS treatment visits over 2 weeks, a clinical assessment will be done to see if the participants are responding to the iTBS treatment with a targeted language assessment and neuro-imaging as described above. After 2 weeks of "wash-out", where the subjects do not receive any treatments, the participants will undergo another 2 weeks of iTBS treatment. On the first iTBS session after the 2-week washout period, participants will undergo a targeted language assessment and EEG/fNIRS. At the final iTBS session at 6 weeks, subjects will again undergo a targeted language assessment, EEG/fNIRS, and fMRI. At that point, after 6 weeks, the cross-over study is finished.

Conditions

Primary Progressive Nonfluent Aphasia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active iTBS

Device: MagPro X100 stimulator equipped with the B65 fluid-cooled coil for dominant Inferior Frontal Gyrus (IFG) stimulation (MagPro, Medtronic).

Intervention: 10 sessions daily of iTBS over 2 weeks. Active-iTBS consists of intermittent Theta Burst Stimulation to the dominant IFG (120% of resting motor threshold, bursts of 3 pulses at 50 Hz, bursts repeated at 5 Hz for 600 pulses total over 3 min).

Group Type: ACTIVE_COMPARATOR

Active iTBS

Intervention Type: DEVICE

Intermittent theta burst transcranial magnetic stimulation

Sham iTBS

Device: MagPro X100 stimulator applied to dominant inferior frontal lobe.

Intervention: 10 sessions daily of sham iTBS over 2 weeks. Sham sessions involve a click replicating the sound of the magnetic discharge, without any magnetic pulse being delivered.

Group Type: SHAM_COMPARATOR

Sham iTBS

Intervention Type: DEVICE

Sham intervention

Interventions

Active iTBS

Intermittent theta burst transcranial magnetic stimulation

Intervention Type: DEVICE

Sham iTBS

Sham intervention

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Clinically diagnosed with nonfluent-agrammatic variant primary progressive aphasia (nfvPPA), by 2011 Gorno-Tempini diagnostic criteria.
• Frontotemporal lobar degeneration modified clinical dementia rating scale (FTLD-CDR) score ≤4 (mild).
• Is voluntary and competent to consent to treatment, or if demented, to assent and co-consent can be obtained by their legal next-of-kin, legal guardian, or substitute decision maker.
• Speaks English enough to be able to complete neuropsychological testing.
• Able to adhere to the treatment schedule.
• Has a study partner available to answer the Progressive Aphasia Severity Scale (PASS) questionnaire.

Exclusion Criteria

• Uncorrected visual or hearing impairment by self report.
• History of substance dependence or abuse within the last 3 months.
• Has active suicidal intent.
• Has a lifetime Mini-International Neuropsychiatric Interview (MINI) diagnosis of major depressive disorder, bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms.
• Concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump.
• Any significant neurological disorder other than nfvPPA including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, history of epilepsy, known cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than or equal to 5 minutes in the previous 6 months.
• Is currently (or in the last 4 weeks) taking lorazepam greater than 2 mg daily (or equivalent) or any dose of an anticonvulsant, due to the potential to limit rTMS efficacy.

• Does not pass the TMS adult safety screening (TASS) questionnaire (e.g. has an intracranial implant)

• Severe claustrophobia.
• Cardiac pacemakers or ferromagnetic implants.
• Pregnant women.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of British Columbia

OTHER

Sponsor Role: lead

Responsible Party

Fidel Vila-Rodriguez

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fidel Vila-Rodriguez, MD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Locations

Non-Invasive Neurostimulation Therapies lab, University of British Columbia

Vancouver, British Columbia, Canada

Countries

Canada

Other Identifiers

H16-01327

Identifier Type: -

Identifier Source: org_study_id