Primary Progressive AphasiaRECONNECTNCT05842473
Long-term Effect of TMS in Primary Progressive Aphasia
A study testing Transcranial Magnetic Stimulation (active) and Language therapy in people with Primary Progressive Aphasia and Frontotemporal Dementia, run by Hospital San Carlos, Madrid at 1 site in Spain.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Progressive Aphasia, Frontotemporal Dementia, Alzheimer Disease
- What is being tested?
- Transcranial Magnetic Stimulation (active) and Language therapy
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 63 participants
- Where
- 1 siteSpain
- Study dates
- 1 Feb 2023to 31 Jul 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of PPA (Gorno-Tempini et al. 2011 criteria supported by neuroimaging)
- CDR
- Language is the most prominent symptom
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Being tested
- Transcranial Magnetic Stimulation (active), Language therapy, Transcranial Magnetic Stimulation (sham)
- Keywords
- brain stimulation, transcranial magnetic stimulation
- Medical subject headings
- Aphasia, Primary Progressive, Frontotemporal Dementia, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic Stimulation (active)Device
Theta-burst transcranial magnetic stimulation (active) delivered over the left dorsolateral prefrontal cortex. Daily sessions for two weeks followed by 1 session per week.
Language therapyBehavioural
Language therapy immediately after each TMS session. Daily sessions for two weeks followed by 1 session per week.
Transcranial Magnetic Stimulation (sham)Device
Theta-burst transcranial magnetic stimulation (sham) delivered over the left dorsolateral prefrontal cortex. Daily sessions for two weeks followed by 1 session per week.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Behavioral: Language therapy; Device: Transcranial Magnetic Stimulation (sham) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brain Metabolism
Changes in FDG-PET imaging (Standard Uptake Value ratio)
Measured: 0 and 6 months
Secondary outcomes (5)
Spontaneous language
Changes in Words per minute
Measured: 0, 3 and 6 months
Language assessment (Mini-Linguistic State Examination)
Changes in Mini-Linguistic State Examination test
Measured: 0, 3 and 6 months
Language assessment (trained words)
Changes in trained words accuracy (number of words)
Measured: 0, 3 and 6 months
Daily-living activities
Changes in Interview for Deterioration in Daily living in Dementia Scale
Measured: 0, 3 and 6 months
Neuropsychiatric symptoms
Changes in Neuropsychiatric Inventory scale
Measured: 0, 3 and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2023
- Study start1 Feb 2023
- Primary completion31 Jul 2024
- Study completion31 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary Progressive AphasiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital San Carlos, Madrid
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jordi A Matias-Guiu, Hospital San Carlos, Madrid
- Investigators
- Jordi A Matias-Guiu, PhD, Principal investigator, Hospital Clinico San Carlos
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05842473
- Sponsor's protocol ID
- 21/731-EC_P
- Acronym
- RECONNECT
- Status last verified
- Dec 2024
- First submitted
- 24 Apr 2023
- Last updated
- 18 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 40788648
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long-term Effect of Transcranial Magnetic Stimulation in Primary Progressive Aphasia
- ClinicalTrials.gov ID
- NCT05842473
- Acronym / sponsor ID
- RECONNECT / 21/731-EC_P
- Keywords
- brain stimulation, transcranial magnetic stimulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- Hospital San Carlos, MadridUniversity, hospital or other
- Study start
- 1 Feb 2023 (actual)
- Primary completion
- 31 Jul 2024 (actual)
- Study completion
- 31 Jul 2024 (actual)
- First posted
- 6 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TMS active + language therapy | Active comparator | Device: Transcranial Magnetic Stimulation (active), Behavioral: Language therapyTMS (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 | Sham comparator | Behavioral: Language therapy, Device: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of PPA (Gorno-Tempini et al. 2011 criteria supported by neuroimaging)
- CDR
- Language is the most prominent symptom
Key exclusion criteria (11 listed)
- Clinical Dementia Rating scale > 1
- History of epilepsy or epileptiform activity in EEG
- Another disorder causing aphasia
- Any contraindication for TMS
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Device | TMS active + language therapy |
| Language therapyLanguage therapy immediately after each TMS session. Daily sessions for two weeks followed by 1 session per week. | Behavioural | TMS active + language therapy, TMS sham + language therapy |
| 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. | Device | TMS sham + language therapy |
Primary outcome
Brain Metabolism
Time frame: 0 and 6 months
Changes in FDG-PET imaging (Standard Uptake Value ratio)
5 secondary outcomes
Spontaneous language
Time frame: 0, 3 and 6 months
Language assessment (Mini-Linguistic State Examination)
Time frame: 0, 3 and 6 months
Language assessment (trained words)
Time frame: 0, 3 and 6 months
Daily-living activities
Time frame: 0, 3 and 6 months
Neuropsychiatric symptoms
Time frame: 0, 3 and 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2024.
- Derived from this study: PubMed 40788648Fernandez-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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jordi A Matias-Guiu, PhD principal investigator
Hospital Clinico San Carlos
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Magnetic Stimulation (active) and Language therapy in people with Primary Progressive Aphasia and Frontotemporal Dementia, run by Hospital San Carlos, Madrid at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brain Metabolism (time frame: 0 and 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05842473, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2024.