Primary Progressive Aphasia(PPA)RECONNECT-PLUSNCT07158216
Long Term Effect of Brain Stimulation in PPA
A study testing TMS and tDCS in people with Primary Progressive Aphasia(PPA), run by Hospital San Carlos, Madrid at 1 site in Spain.
Trial summary
The goal of this clinical trial is to investigate the effect of non-invasive brain stimulation techniques in the progression of primary progressive aphasia for 6 months. We will compare three modalities of brain stimulation (TMS, tDCS, TMS+tDCS) against sham stimulation. All patients will receive also language therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Progressive Aphasia(PPA)
- What is being tested?
- TMS and tDCS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteSpain
- Study dates
- 15 Sep 2025to Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 according to the current consensus criteria proposed by Gorno-Tempini et al., 2011), based on the presence of progressive language impairment as the most prominent and primary cause of functional decline and the exclusion of other medical, psychiatric, or non-neurodegenerative causes,a s well as early prominent memory, visuoperceptual or behavioral disturbances;
- Diagnosis of one of the three variants of PPA (non-fluent, semantic, or logopenic) according to the consensus criteria (Gorno-Tempini et al., 2011), based on the language profile and supported by neuroimaging (FDG-PET or MRI).
- Clinical Dementia Rating scale equal or less than 1;
- The language impairment is the main neurological deficit for the patient.
Who cannot join
- Patient diagnosed with a condition other than PPA that could cause language impairment;
- History of epilepsy or presence of focal epileptiform pathology on EEG recording; ·Contraindications related to the treatments or procedures to be used (TMS and tDCS), such as ferromagnetic material, pregnancy, or breastfeeding;
- Terminal illness or active malignancy;
- Alcohol or substance abuse within the past year;
- Major psychiatric disorders (schizophrenia, schizoaffective disorders, bipolar disorder, obsessive-compulsive disorder, or personality disorders);
- Absolute inability to communicate (mutism), or poor command of the language that, in the investigator's judgment, would prevent participation in the study;
Show all 14Show fewer
- Severity of PPA that prevents participation in interventions or assessments at the time of inclusion;
- Participation in another clinical trial within the previous 4 months;
- Chronic use of medications that could affect study outcomes;
- Antiepileptic drugs: allowed if on stable doses for at least 3 months before inclusion. If needed during the study due to seizure occurrence, they may be added;
- Diazepam and derivatives: permitted only if on stable doses for at least 3 months before inclusion. Dose adjustments during the study are allowed;
- Donepezil, Galantamine, Rivastigmine, and Memantine: allowed if on stable doses for at least 3 months before inclusion;
- SSRIs (Selective Serotonin Reuptake Inhibitors): permitted only if on stable doses for at least 3 months prior to inclusion. If necessary during the study, they may be added;
- Medications that may lower the seizure threshold (e.g., tricyclic antidepressants, antipsychotics): allowed if on stable doses for at least 3 months before inclusion.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Spain1 site, 1 recruiting
- Recruiting
Hospital Clinico San Carlos
Madrid
Jordi Matias-Guiu, PhD MD, +34913303000, jordi.matias-guiu@salud.madrid.org
About this study
Official title: Long-term Effect of Transcranial Magnetic Stimulation and Transcranial Electrical Stimulation in Primary Progressive Aphasia: Randomized, Double-blind Clinical Trial (RECONNECT-PLUS)
The goal of this clinical trial is to investigate the effect of non-invasive brain stimulation techniques in the progression of primary progressive aphasia for 6 months. We will compare three modalities of brain stimulation (TMS, tDCS, TMS+tDCS) against sham stimulation. All patients will receive also language therapy.
Read the detailed description
Transcranial Magnetic Stimulation will follow an intermitent theta-burst protocol targetting the left dorsolateral prefrontal cortex. Transcranial electrical stimulation will also follow an excitatory protocol over the same region. All brain stimulation procedures will be conducted under neuronavigation. Language therapy will follow the lexical retrieval cascade protocol and will be conducted after each brain stimulation session.
- Conditions
- Primary Progressive Aphasia(PPA)
- Being tested
- TMS, tDCS, Sham TMS, Sham tDCS
- Keywords
- Primary progressive aphasia, Frontotemporal dementia, Alzheimer's disease, Brain stimulation, Transcranial Magnetic Stimulation, Transcranial direct current stimulation, Transcranial electrical stimulation
- Medical subject headings
- Aphasia, Primary Progressive, Frontotemporal Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMSDevice
Active TMS + sham tDCS. All patients will receive language therapy immediately after brain stimulation. The period of treatment will be 6 months, comprising 10 consecutive sessions in two weeks (intensive period) followed by once per week (maintenance period of 22 weeks)
tDCSDevice
sham TMS + active tDCS. All patients will receive language therapy immediately after brain stimulation. The period of treatment will be 6 months, comprising 10 consecutive sessions in two weeks (intensive period) followed by once per week (maintenance period of 22 weeks)
Sham TMSDevice
Sham TMS. All patients will receive language therapy immediately after brain stimulation. The period of treatment will be 6 months, comprising 10 consecutive sessions in two weeks (intensive period) followed by once per week (maintenance period of 22 weeks)
Sham tDCSDevice
Sham tDCS. All patients will receive language therapy immediately after brain stimulation. The period of treatment will be 6 months, comprising 10 consecutive sessions in two weeks (intensive period) followed by once per week (maintenance period of 22 weeks)
| Study group | Role | What they receive |
|---|---|---|
| active TMS + active tDCS | Experimental | Not described Receives: Device: TMS; Device: tDCS |
| active TMS + sham tDCS | Experimental | Not described Receives: Device: TMS; Device: Sham tDCS |
| sham TMS + active tDCS | Experimental | Not described Receives: Device: tDCS; Device: Sham TMS |
| sham TMS + sham tDCS | Sham comparator | Not described Receives: Device: Sham TMS; Device: Sham tDCS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mini-Linguistic State Examination
Measured: 6 months
Secondary outcomes (7)
Naming of trained words
It will be evaluated using a list of 261 words from eight semantic categories (animals, food, objects, places, furniture, clothing, transportation, and body parts)
Measured: 6 monhts
ACE-III
General cognition
Measured: 6 months
Interview for Deterioration in Daily Living Activities in Dementia (IDDD)
Functional activities
Measured: 6 months
Communicative Effectiveness Index (CETI)
Functional communication questionnaire
Measured: 6 months
CDR(R) plus NACC FTLD-SB
Clinical Dementia Rating
Measured: 6 months
Neuropsychiatric Inventory (NPI)
Neuropsychiatric symptoms
Measured: 6 months
FDG-PET imaging
Regional brain metabolism in a region of interest capturing a large part of the left hemisphere and associated with clinical decline in PPA (Fernandez-Romero et al. 2025)
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2025
- Study start15 Sep 2025
- Primary completionDec 2028 (estimated)
- Study completionDec 2028 (estimated)
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 Aphasia(PPA)Studies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07158216
- Sponsor's protocol ID
- Hospital Clinico San Carlos
- Acronym
- RECONNECT-PLUS
- Status last verified
- Apr 2026
- First submitted
- 28 Aug 2025
- Last updated
- 23 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Fernandez-Romero L, Diez-Cirarda M, Delgado-Alonso C, Cabrera-Martin MN, Gonzalez-Rosa JJ, Sanz-Nieto C, Perez-Macias N, Balugo P, Gomez-Ruiz N, Matias-Guiu J, Portoles-Perez A, Matias-Guiu JA. Long-term effect of transcranial magnetic stimulation and transcranial electrical stimulation in primary progressive aphasia: study protocol for a randomised, double-blind clinical trial (RECONNECT-PLUS). BMJ Open. 2026 May 20;16(5):e112999. doi: 10.1136/bmjopen-2025-112999.
PubMed 42161537
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long-term Effect of Transcranial Magnetic Stimulation and Transcranial Electrical Stimulation in Primary Progressive Aphasia: Randomized, Double-blind Clinical Trial (RECONNECT-PLUS)
- ClinicalTrials.gov ID
- NCT07158216
- Acronym / sponsor ID
- RECONNECT-PLUS / Hospital Clinico San Carlos
- Conditions
- Primary Progressive Aphasia(PPA)
- Keywords
- Primary progressive aphasia, Frontotemporal dementia, Alzheimer's disease, Brain stimulation, Transcranial Magnetic Stimulation, Transcranial direct current stimulation, Transcranial electrical stimulation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Hospital San Carlos, MadridUniversity, hospital or other
- Study start
- 15 Sep 2025 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 5 Sep 2025 (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.
The goal of this clinical trial is to investigate the effect of non-invasive brain stimulation techniques in the progression of primary progressive aphasia for 6 months. We will compare three modalities of brain stimulation (TMS, tDCS, TMS+tDCS) against sham stimulation. All patients will receive also language therapy.
Detailed description
Transcranial Magnetic Stimulation will follow an intermitent theta-burst protocol targetting the left dorsolateral prefrontal cortex. Transcranial electrical stimulation will also follow an excitatory protocol over the same region. All brain stimulation procedures will be conducted under neuronavigation. Language therapy will follow the lexical retrieval cascade protocol and will be conducted after each brain stimulation session.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| active TMS + active tDCS | Experimental | Device: TMS, Device: tDCS |
| active TMS + sham tDCS | Experimental | Device: TMS, Device: Sham tDCS |
| sham TMS + active tDCS | Experimental | Device: tDCS, Device: Sham TMS |
| sham TMS + sham tDCS | Sham comparator | Device: Sham TMS, Device: Sham tDCS |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of PPA according to the current consensus criteria proposed by Gorno-Tempini et al., 2011), based on the presence of progressive language impairment as the most prominent and primary cause of functional decline and the exclusion of other medical, psychiatric, or non-neurodegenerative causes,a s well as early prominent memory, visuoperceptual or behavioral disturbances;
- Diagnosis of one of the three variants of PPA (non-fluent, semantic, or logopenic) according to the consensus criteria (Gorno-Tempini et al., 2011), based on the language profile and supported by neuroimaging (FDG-PET or MRI).
- Clinical Dementia Rating scale equal or less than 1;
- The language impairment is the main neurological deficit for the patient.
Key exclusion criteria (14 listed)
- Patient diagnosed with a condition other than PPA that could cause language impairment;
- History of epilepsy or presence of focal epileptiform pathology on EEG recording; ·Contraindications related to the treatments or procedures to be used (TMS and tDCS), such as ferromagnetic material, pregnancy, or breastfeeding;
- Terminal illness or active malignancy;
- Alcohol or substance abuse within the past year;
- Major psychiatric disorders (schizophrenia, schizoaffective disorders, bipolar disorder, obsessive-compulsive disorder, or personality disorders);
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 |
|---|---|---|
| TMSActive TMS + sham tDCS. All patients will receive language therapy immediately after brain stimulation. The period of treatment will be 6 months, comprising 10 consecutive sessions in two weeks (intensive period) followed by once per week (maintenance period of 22 weeks) | Device | active TMS + active tDCS, active TMS + sham tDCS |
| tDCSsham TMS + active tDCS. All patients will receive language therapy immediately after brain stimulation. The period of treatment will be 6 months, comprising 10 consecutive sessions in two weeks (intensive period) followed by once per week (maintenance period of 22 weeks) | Device | active TMS + active tDCS, sham TMS + active tDCS |
| Sham TMSSham TMS. All patients will receive language therapy immediately after brain stimulation. The period of treatment will be 6 months, comprising 10 consecutive sessions in two weeks (intensive period) followed by once per week (maintenance period of 22 weeks) | Device | sham TMS + active tDCS, sham TMS + sham tDCS |
| Sham tDCSSham tDCS. All patients will receive language therapy immediately after brain stimulation. The period of treatment will be 6 months, comprising 10 consecutive sessions in two weeks (intensive period) followed by once per week (maintenance period of 22 weeks) | Device | active TMS + sham tDCS, sham TMS + sham tDCS |
Primary outcome
Mini-Linguistic State Examination
Time frame: 6 months
7 secondary outcomes
Naming of trained words
Time frame: 6 monhts
ACE-III
Time frame: 6 months
Interview for Deterioration in Daily Living Activities in Dementia (IDDD)
Time frame: 6 months
Communicative Effectiveness Index (CETI)
Time frame: 6 months
CDR(R) plus NACC FTLD-SB
Time frame: 6 months
Neuropsychiatric Inventory (NPI)
Time frame: 6 months
FDG-PET imaging
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2026.
- Derived from this study: PubMed 42161537Fernandez-Romero L, Diez-Cirarda M, Delgado-Alonso C, Cabrera-Martin MN, Gonzalez-Rosa JJ, Sanz-Nieto C, Perez-Macias N, Balugo P, Gomez-Ruiz N, Matias-Guiu J, Portoles-Perez A, Matias-Guiu JA. Long-term effect of transcranial magnetic stimulation and transcranial electrical stimulation in primary progressive aphasia: study protocol for a randomised, double-blind clinical trial (RECONNECT-PLUS). BMJ Open. 2026 May 20;16(5):e112999. doi: 10.1136/bmjopen-2025-112999.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TMS and tDCS in people with Primary Progressive Aphasia(PPA), 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 4 inclusion and 14 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: looking for participants now, as of the sponsor's last update on 23 Apr 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jordi Matias-Guiu, PhD MD (+34913303000, jordi.matias-guiu@salud.madrid.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mini-Linguistic State Examination (time frame: 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 NCT07158216, 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 23 Apr 2026; AzTrials last refreshed its copy on 26 Oct 2026.