NCT05842473

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
63

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Feb 2023

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2023

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

April 24, 2023

Completed
12 days until next milestone

First Posted

Study publicly available on registry

May 6, 2023

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2024

Completed
Last Updated

December 18, 2024

Status Verified

December 1, 2024

Enrollment Period

1.5 years

First QC Date

April 24, 2023

Last Update Submit

December 15, 2024

Conditions

Keywords

brain stimulationtranscranial magnetic stimulation

Outcome Measures

Primary Outcomes (1)

  • Brain Metabolism

    Changes in FDG-PET imaging (Standard Uptake Value ratio)

    0 and 6 months

Secondary Outcomes (5)

  • Spontaneous language

    0, 3 and 6 months

  • Language assessment (Mini-Linguistic State Examination)

    0, 3 and 6 months

  • Language assessment (trained words)

    0, 3 and 6 months

  • Daily-living activities

    0, 3 and 6 months

  • Neuropsychiatric symptoms

    0, 3 and 6 months

Study Arms (2)

TMS active + language therapy

ACTIVE COMPARATOR

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)Behavioral: Language therapy

TMS sham + language therapy

SHAM COMPARATOR

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 therapyDevice: Transcranial Magnetic Stimulation (sham)

Interventions

Theta-burst transcranial magnetic stimulation (active) delivered over the left dorsolateral prefrontal cortex. Daily sessions for two weeks followed by 1 session per week.

TMS active + language therapy

Language therapy immediately after each TMS session. Daily sessions for two weeks followed by 1 session per week.

TMS active + language therapyTMS sham + language therapy

Theta-burst transcranial magnetic stimulation (sham) delivered over the left dorsolateral prefrontal cortex. Daily sessions for two weeks followed by 1 session per week.

TMS sham + language therapy

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hospital ClĂ­nico San Carlos.

Madrid, Madrid, 28040, Spain

Location

Related Publications (1)

  • Fernandez-Romero L, Cabrera-Martin MN, Delgado-Alonso C, Suarez-Coalla P, Grasso SM, Portoles A, Perez-Macias N, Carreras MT, Diez-Cirarda M, Gil-Moreno MJ, Olazaran J, Vieira A, Oliver-Mas S, Gomez-Pinedo U, Matias-Guiu J, Matias-Guiu JA. Long-Term Therapy With Transcranial Magnetic Stimulation in Primary Progressive Aphasia: A Randomized Clinical Trial. JAMA Netw Open. 2025 Aug 1;8(8):e2526129. doi: 10.1001/jamanetworkopen.2025.26129.

MeSH Terms

Conditions

Aphasia, Primary ProgressiveFrontotemporal DementiaAlzheimer Disease

Interventions

Transcranial Magnetic StimulationLanguage Therapy

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesAphasiaSpeech DisordersLanguage DisordersCommunication DisordersNeurobehavioral ManifestationsNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and SymptomsNeurocognitive DisordersMental DisordersFrontotemporal Lobar DegenerationTDP-43 ProteinopathiesNeurodegenerative DiseasesProteostasis DeficienciesMetabolic DiseasesNutritional and Metabolic DiseasesTauopathies

Intervention Hierarchy (Ancestors)

Magnetic Field TherapyTherapeuticsRehabilitation of Speech and Language DisordersRehabilitationAftercareContinuity of Patient CarePatient Care

Study Officials

  • Jordi A Matias-Guiu, PhD

    Hospital Clinico San Carlos

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

April 24, 2023

First Posted

May 6, 2023

Study Start

February 1, 2023

Primary Completion

July 31, 2024

Study Completion

July 31, 2024

Last Updated

December 18, 2024

Record last verified: 2024-12

Locations