Long-term Effect of TMS in Primary Progressive Aphasia (RECONNECT)

Long-term Effect of Transcranial Magnetic Stimulation in Primary Progressive Aphasia

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Alzheimer Disease; Frontotemporal Dementia; Primary Progressive Aphasia
• Intervention / Treatment: Device: Transcranial Magnetic Stimulation (active); Behavioral: Language therapy; Device: Transcranial Magnetic Stimulation (sham)

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jordi A Matias-Guiu, PhD MD; Phone Number: 3711 913303000; Email: jordi.matias-guiu@salud.madrid.org

Study Locations

• Spain
  • Madrid, Spain, 28040
    • Hospital Clínico San Carlos.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: TMS active + 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.	Device: Transcranial Magnetic Stimulation (active); Theta-burst transcranial magnetic stimulation (active) delivered over the left dorsolateral prefrontal cortex. Daily sessions for two weeks followed by 1 session per week.; Behavioral: Language therapy; Language therapy immediately after each TMS session. Daily sessions for two weeks followed by 1 session per week.
Sham Comparator: TMS sham + 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.	Behavioral: Language therapy; Language therapy immediately after each TMS session. Daily sessions for two weeks followed by 1 session per week.; Device: Transcranial Magnetic Stimulation (sham); Theta-burst transcranial magnetic stimulation (sham) delivered over the left dorsolateral prefrontal cortex. Daily sessions for two weeks followed by 1 session per week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain Metabolism	Changes in FDG-PET imaging (Standard Uptake Value ratio)	0 and 6 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Hospital San Carlos, Madrid
• Investigators: Principal Investigator: Jordi A Matias-Guiu, PhD, Hospital Clinico San Carlos

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: April 24, 2023
• First Submitted That Met QC Criteria: April 24, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 28, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: brain stimulation; transcranial magnetic stimulation
• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Dementia; Tauopathies; Language Disorders; Communication Disorders; Speech Disorders; Frontotemporal Lobar Degeneration; Alzheimer Disease; Aphasia; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain
• Other Study ID Numbers: 21/731-EC_P

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No