Alzheimer Disease, Frontotemporal Dementia, Primary Progressive Aphasia
Conditions
Keywords
brain stimulation, transcranial magnetic stimulation
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.
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.
BEHAVIORALLanguage therapy
Language therapy immediately after each TMS session. Daily sessions for two weeks followed by 1 session per week.
Theta-burst transcranial magnetic stimulation (sham) delivered over the left dorsolateral prefrontal cortex. Daily sessions for two weeks followed by 1 session per week.
Sponsors
Hospital San Carlos, Madrid
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain Metabolism | 0 and 6 months | Changes in FDG-PET imaging (Standard Uptake Value ratio) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Spain
Outcome results
None listed