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RecruitingNCT07158216RECONNECT-PLUSUpdated Apr 23, 2026

Long Term Effect of Brain Stimulation in PPA

An interventional study of TMS and tDCS in Primary Progressive Aphasia(PPA), sponsored by Hospital San Carlos, Madrid. Recruiting at 1 site in Spain. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-23.

Sponsored by Hospital San Carlos, Madrid · Not applicable, Interventional, and Treatment

From the registry’s dates

  • Started Sep 2025; still recruiting 1 year 1 month later.
Phase
Not applicable
Study type
Interventional
Enrollment
80
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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 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.

02

Conditions studied

  • 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
03

In context

Aphasia, Primary Progressive

77 studies on the registry are indexed under Aphasia, Primary Progressive; 29 are open to participants now.

This study's planned enrollment of 80 is above the median of 30 across 60 interventional studies indexed under Aphasia, Primary Progressive.

Browse Aphasia, Primary Progressive studies →

Lead sponsor

Hospital San Carlos, Madrid is the lead sponsor of 74 studies on the registry; 17 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • 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.

Exclusion criteria

Exclusion Criteria:

  • 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; · related to the treatments or procedures to be used (TMS and tDCS), such as ferromagnetic material, pregnancy, or breastfeeding;
  • Terminal illness or active ;
  • 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;
  • 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.
Terms in these criteria, in plain language(2)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
80 participants (estimated)

Study arms

  • Experimental
    active TMS + active tDCS

    Device: TMS · Device: tDCS

  • Experimental
    active TMS + sham tDCS

    Device: TMS · Device: Sham tDCS

  • Experimental
    sham TMS + active tDCS

    Device: tDCS · Device: Sham TMS

  • Sham comparator
    sham TMS + sham tDCS

    Device: Sham TMS · Device: Sham tDCS

Interventions

  • DeviceTMS

    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)

  • DevicetDCS

    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)

  • DeviceSham TMS

    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)

  • DeviceSham tDCS

    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)

06

What researchers measure

Primary outcomes

  1. Mini-Linguistic State Examination

    Time frame: 6 months

Secondary outcomes

  1. 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)

    Time frame: 6 monhts

  2. ACE-III

    General cognition

    Time frame: 6 months

  3. Interview for Deterioration in Daily Living Activities in Dementia (IDDD)

    Functional activities

    Time frame: 6 months

  4. Communicative Effectiveness Index (CETI)

    Functional communication questionnaire

    Time frame: 6 months

  5. CDR(R) plus NACC FTLD-SB

    Clinical Dementia Rating

    Time frame: 6 months

  6. Neuropsychiatric Inventory (NPI)

    Neuropsychiatric symptoms

    Time frame: 6 months

  7. 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)

    Time frame: 6 months

07

Study locations

1 of 1 sites recruiting
08

References and documents

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 ↗
09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Started Sep 2025 (actual). Primary completion is estimated for Dec 2028, 39 months after the start.

Of 38 non-industry interventional studies with no phase under Aphasia, Primary Progressive, half reached primary completion within 41 months of starting (the median), counting those still running; a quarter within 26 and three quarters within 59. This study's planned 39 months is close to that.

Counting every sponsor, half of 38 studies reached it within 41 months; a quarter within 26 and three quarters within 59.

How these figures are worked out, and which studies are left out of them.

Registered
Aug 28, 2025
First posted
Sep 5, 2025
StartActual
Sep 15, 2025
Primary completionEst.
Dec 2028
CompletionEst.
Dec 2028
Last update
Apr 23, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Apr 23, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT07158216
Lead sponsor
Hospital San Carlos, Madrid
Responsible party
Jordi A Matias-Guiu (MD PhD Neurologist, Hospital San Carlos, Madrid) — Principal investigator
First posted
Sep 5, 2025
Start date
Sep 15, 2025
Primary completion
Dec 2028 (estimated)
Completion
Dec 2028 (estimated)
Last update
Apr 23, 2026

Study contacts

Jordi Matias-Guiu, PhD MD
Contact
jordi.matias-guiu@salud.madrid.org
+34913303000

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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