Long-term Effect of TMS in Primary Progressive Aphasia

Not Applicable

Completed

• Conditions: Alzheimer Disease; Primary Progressive Aphasia; Frontotemporal Dementia
• Interventions: Device: Transcranial Magnetic Stimulation (active); Device: Transcranial Magnetic Stimulation (sham); Behavioral: Language therapy

• Registration Number: NCT05842473
• Lead Sponsor: Hospital San Carlos, Madrid

Brief Summary

There are very few treatments for neurodegenerative disorders, and the efficacy of these treatments is generally modest. Recent studies have shown a short-term positive effect of non-invasive neuromodulation techniques such as transcranial magnetic stimulation (TMS) in primary progressive aphasia (PPA). PPA is a clinical syndrome associated with Alzheimer's disease and Frontotemporal degeneration. The aim of this study is to compare the effect of TMS and language therapy versus language therapy and sham TMS in patients with PPA during 6 months. A prospective, randomized, controlled, double-blind and parallel clinical trial will be conducted. The changes in brain metabolism using FDG-PET, language, neuropsychiatric symptoms, and daily-living activities will be assessed. Connectivity changes using electroencephalography will also be examined. In addition, a subgroup of patients will be assessed with multimodal MRI (structural and functional), and blood biomarkers. As a result of this project, valuable information about the long-term efficacy of non-invasive brain stimulation in PPA will be obtained, as well as the mechanisms of the therapy and clinical and neuroimaging factors associated with therapy response.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-02-01
• Study First Submitted: 2023-04-24
• Study First Submitted QC: 2023-04-24
• Study First Posted: 2023-05-06
• Primary Completion: 2024-07-31
• Study Completion: 2024-07-31
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-15
• Last Update Posted: 2024-12-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 63

Inclusion Criteria

• Diagnosis of PPA (Gorno-Tempini et al. 2011 criteria supported by neuroimaging)
• CDR
• Language is the most prominent symptom

Exclusion Criteria

• Clinical Dementia Rating scale > 1
• History of epilepsy or epileptiform activity in EEG
• Another disorder causing aphasia
• Any contraindication for TMS
• Pregnancy
• Medical disorder with a life expectancy of less than one year
• Malignancy in the last two years
• Alcohol or drug abuse
• Major psychiatric disorder
• Inability to communicate (mutism)
• Use of anticonvulsants, benzodiazepines, donepezil/galantamine/rivastigmine, memantine, antidepressants and neuroleptics is permitted if they are at stable doses in the last three months.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TMS active + language therapy	Transcranial Magnetic Stimulation (active)	TMS (active) using theta burst protocol over the left dorsolateral prefrontal cortex. Daily sessions for two weeks followed by one session per week during 6 months. Each TMS session is followed by language training.
TMS sham + language therapy	Transcranial Magnetic Stimulation (sham)	TMS (sham) using theta burst protocol over the left dorsolateral prefrontal cortex. Daily sessions for two weeks followed by one session per week during 6 months. Each TMS session is followed by language training.
TMS active + language therapy	Language therapy	TMS (active) using theta burst protocol over the left dorsolateral prefrontal cortex. Daily sessions for two weeks followed by one session per week during 6 months. Each TMS session is followed by language training.
TMS sham + language therapy	Language therapy	TMS (sham) using theta burst protocol over the left dorsolateral prefrontal cortex. Daily sessions for two weeks followed by one session per week during 6 months. Each TMS session is followed by language training.

Primary Outcome Measures

Name	Time	Method
Brain Metabolism	0 and 6 months	Changes in FDG-PET imaging (Standard Uptake Value ratio)

Secondary Outcome Measures

Name	Time	Method
Spontaneous language	0, 3 and 6 months	Changes in Words per minute
Language assessment (Mini-Linguistic State Examination)	0, 3 and 6 months	Changes in Mini-Linguistic State Examination test
Language assessment (trained words)	0, 3 and 6 months	Changes in trained words accuracy (number of words)
Daily-living activities	0, 3 and 6 months	Changes in Interview for Deterioration in Daily living in Dementia Scale
Neuropsychiatric symptoms	0, 3 and 6 months	Changes in Neuropsychiatric Inventory scale

Trial Locations

Locations (1)

Hospital Clínico San Carlos.; 🇪🇸 Madrid, Spain