Transcranial Magnetic Stimulation in Nonfluent/Agrammatic Variant Primary Progressive Aphasia

NCT03153540 | Terminated

• 1 other identifier: H16-01327
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Primary Progressive Nonfluent Aphasia

Keywords

Aphasia; Agrammatism; Frontotemporal Dementia; Tauopathies; Neurodegenerative Diseases; Language Disorders; Frontotemporal Lobar Degeneration

Outcome Measures

Primary Outcomes (3)

• Incidence of treatment-emergent adverse events

  Safety will be measured by incidence of treatment-emergent adverse events

  6 weeks

• Tolerability levels according to the daily Comfort Rating Questionnaire (CRQ)

  Tolerability will be measured by daily Comfort Rating Questionnaire (CRQ) between sham and active interventions and compared using Chi-square. A mean score across all treatment sessions above 6 on more than 2 items on the CRQ will be considered as severe. A mean score across all treatment sessions between 4 and 6 on more than 2 items on the CRQ will be considered as moderate tolerability. A mean score across all treatment sessions below 4 on the majority of items will be considered as mild tolerability.

  6 weeks

• Drop out rate

  Feasibility will be measured by drop out rate. A drop out rate \>50% will be considered as an indication of non-feasibility of current protocol.

  6 weeks

Secondary Outcomes (12)

• Changes in the Verb and Object Naming Test score

  6 weeks

• Changes in the Make a Sentence Test score

  6 weeks

• Changes in the Sentence Comprehension Test score

  6 weeks

• Changes in the Apraxia of Speech Rating Scale score

  6 weeks

• Changes in the Clinical Global Impression of Change score

  6 weeks

Study Arms (2)

Active iTBS

ACTIVE COMPARATOR

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).

Device: Active iTBS

Sham iTBS

SHAM COMPARATOR

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.

Device: Sham iTBS

Interventions

Active iTBS DEVICE

Intermittent theta burst transcranial magnetic stimulation

Active iTBS

Sham iTBS DEVICE

Sham intervention

Sham iTBS

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (1)

Non-Invasive Neurostimulation Therapies lab, University of British Columbia

Vancouver, British Columbia, V6T2A1, Canada

Location

MeSH Terms

Conditions

Primary Progressive Nonfluent Aphasia; Aphasia; Aphasia, Broca; Frontotemporal Dementia; Tauopathies; Neurodegenerative Diseases; Language Disorders; Frontotemporal Lobar Degeneration

Condition Hierarchy (Ancestors)

Aphasia, Primary Progressive; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Speech Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Study Officials

• Fidel Vila-Rodriguez, MD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: March 1, 2017
• First Posted: May 15, 2017
• Study Start: September 1, 2018
• Primary Completion: February 14, 2022
• Study Completion: February 14, 2022
• Last Updated: March 3, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)