Clinical Research Directory

Speech and Language Interventions for Italian People With PPA

Primary progressive aphasia (PPA) is an umbrella term used to refer to several clinical variants that manifest as an insidious deterioration of speech/language skills, usually due to frontotemporal lobar degeneration and/or Alzheimer's disease. Consensus criteria have been proposed by an international community regarding the sub-classification of PPA into three variants: (1) semantic variant PPA, characterized by impaired confrontation naming and single-word comprehension; (2) logopenic variant PPA), characterised by word-finding difficulties and sentence repetition deficits; and (3) non-fluent variant, characterised by agrammatism with or without apraxia of speech. Speech and language therapists (SLTs) play a crucial role in the diagnostic process and in setting a therapeutic path along with monitoring the evolution of the clinical picture. Despite growing evidence supporting the benefits of speech-language intervention, the frequency with which individuals with PPA are referred for speech and language services, is suboptimal likely due to skepticism regarding the value of speech and language therapy in the context of neurodegeneration, the scarcity of SLTs with expertise in the treatment of PPA, the lack of awareness regarding the role of the SLT amongst referrers, and the geographical barriers that impede access to in-person speech and language services. In Italy, patients with PPA are rarely offered treatment options due to a lack of understanding of the disorder on the part of health professionals and erroneous assumptions regarding the utility of treatment in patients facing a worsening prognosis. The primary aim of this pilot study is to develop tailored speech and language interventions for patients with different variants of PPA by addressing their linguistic and cognitive difficulties. Secondly, to explore the intervention's effect also on untreated tasks and assess the long-term maintenance of the proposed interventions by monitoring patients for up to six months. Finally, in each PPA variant, the investigators aim to investigate which variables among the sociodemographic, clinical, linguistic/cognitive, and brain MRI features at baseline predict successful clinical results, as well as which structural and functional brain changes are associated with speech and language improvements.

UPenn Observational Research Repository on Neurodegenerative Disease

The aim of this study is to create a repository of both cross-sectional and longitudinal data, including cognitive, linguistic, imaging and biofluid biological specimens, for neurodegenerative disease research and treatment.

Remotely-supervised Neuromodulation in PPA

The goal of this clinical trial is to learn whether remotely-supervised transcranial direct-current stimulation (RS-tDCS) can improve speech and language treatments for individuals with logopenic variant primary progressive aphasia (lvPPA). tDCS is a form of brain stimulation where a low-level electrical current is delivered to the brain through electrodes placed on the head. The main questions the trial aims to answer are: * Is it feasible to do RS-tDCS with virtual speech therapy? * How can brain magnetic resonance imaging scans (MRIs) predict how well someone will benefit from RS-tDCS with virtual speech therapy? Researchers will compare active RS-tDCS stimulation to sham stimulation (where there is no active stimulation, but participants feel stimulation effects at the beginning and end of the session). Participants will: * Travel to either the University of California, San Francisco (UCSF) or the University of Texas at Austin (UT Austin) one time for in-person testing, an MRI scan, and training on how to use the RS-tDCS equipment * Meet with a speech-language pathologist for pre-treatment testing on Zoom for 2 weeks * Participate in speech-language therapy and independent practice on Zoom 5 days a week for 4 weeks, using either active tDCS stimulation or sham * Complete post-treatment testing on Zoom for 1-2 weeks * Complete follow-up testing 2 months after completion of treatment

Intervention for Communication Quality of Life in Primary Progressive Aphasia

The goal of this clinical trial is to determine whether individually tailored speech-language telerehabilitation helps improve communication in people with primary progressive aphasia (PPA), a form of dementia that affects speech and language. The study will be offered to individuals who speak English and/or Spanish. The study will also document how acceptable and beneficial the program is to both patients and their care partners. The main questions the study aims to answer are: 1. Is the telerehabilitation program feasible and acceptable for people with PPA and their care partners? 2. Do participants with PPA and care partners find treatment beneficial? 3. Which outcome measures are most useful for evaluating changes in communication and quality of life? 4. What patterns of treatment response are seen in participants after completing the program? The program includes both speech-language therapy and training for care partners. Participants with PPA will: 1. Complete virtual communication tasks and questionnaires before and after the program 2. Take part in online speech-language therapy sessions 3. Include their care partners in some parts of the program for training and support

Long Term Effect of Brain Stimulation in PPA

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.

Neuroinflammation in FTLD

The goal of this observational study is to investigate the role of neuroinflammation in frontotemporal lobar degeneration (FTLD). The main aims of this study are: 1. To elucidate the role and timing of neuroinflammation in FTLD by using a combination of clinical measures, 7T MRI, and CSF biomarkers; 2. To differentiate FTLD-TDP and FTLD-tau during life using biomarkers for neuroinflammation; 3. To identify biomarkers to predict and monitor disease progression in FTLD; Secondary aim: 1\. To explore the role of brain clearance in the disease process of FTLD. Participants will undergo 7T MRI scans, blood and CSF collection, clinical, neurological, and neuropsychological evaluation.

Targeted Transcranial Magnetic Stimulation to Improve Language and Speech in Patients With Primary Progressive Aphasia

This is a monocenter randomized controlled clinical trial with cross-over arm - assessor blinded. The aims is investigating the effects of the speech language therapy (SLT) alone vs SLT + non-invasive brain stimulation (STIM), using canonic repetitive Transcranial Magnetic Stimulation (rTMS), on speech and language, clinical, neuropsychological, neuroimaging, neurophysiology, and blood features in patients with PPA. The trial will include 45 participants suffering from semantic (svPPA), logopenic (lvPPA) or nonfluent (nfvPPA) variants of Primary Progressive Aphasia (PPA) and 30 healthy controls. At baseline (T0) patients will undergo in-depth clinical, neuropsychological and language assessment, structural and functional magnetic resonance imaging (MRI) scan, electroencephalography (EEG) recording, functional Near Infrared Spectroscopy (fNiRS) scans, and blood sample. PPA patients will be randomized into 2 training groups: the speech language therapy (SLT) group and the SLT + STIM (standard rTMS group or targeted rTMS). The SLT will consist of an online intervention performed through a web-based platform. The training will be tailored to each PPA variant. svPPA and lvPPA will undergo the lexical retrieval cascade (LRC) treatment, while nfvPPA will undergo the Video-implemented Script Training (VISTA). The SLT+ STIM group will perform the same SLT combined with non-invasive stimulation with a cross-over design: canonic repetitive Transcranial Magnetic Stimulation (rTMS) on the left dorsolateral prefrontal cortex (DLPFC) or targeted rTMS in which the site and the protocol of stimulation will be defined based on single-subject EEG combined with functional MRI (EEG+fMRI). This design will aid in determining not only whether non-invasive stimulation can enhance clinical outcomes, but also which non-invasive stimulation is the best to improve results. The SLT training of the SLT group will consist of 2 cycles of training lasting 1 (rest) + 5 (training) weeks, 3 times per week, 1 hour each session, separated by a 12-week washout period. The SLT + standard or targeted STIM groups will undergo 2 cycles of 6-week training, separated by a 12-week washout period with a cross-over design: half of subjects will first receive 6-week SLT training associated with DLPFC rTMS followed by 6-week SLT associated with targeted rTMS, while the other half will follow the reverse order, according to a randomization procedure. After the training (i.e., 6-week visit \[W6\] and 24-week visit \[W24\]), PPA patients will be re-evaluated through neurological, language, neuroimaging/neurophysiology assessments, and blood sample. Evaluations will be also repeated at the 18-week (W18) after the wash-out and before the second cycle of treatment, as well as at 36-week (W36) and 48-week (W48) follow-up visits to assess maintenance of results. MRI and blood sample will be repeated at all visits but W18 and W36. The comprehensive neuropsychological assessment will be repeated at W48 only. 30 healthy controls will also be recruited among the spouses of patients, by word of mouth or through flyers and project awareness campaigns. They will undergo the same assessments administered to PPA patients at T0 (neurological, neuropsychological/language assessments, neuroimaging/neurophysiology, and blood sample). Hypothesis: 1. Patients with PPA who receive a combination of SLT and rTMS will exhibit greater clinical improvement compared to those receiving SLT alone. 2. Choosing the rTMS approach and stimulation site based on individualized MRI and EEG characterization will be more effective as compared to using the standard rTMS approaches described by the literature. 3. The integration of specific clinical, cognitive, language, neuroimaging, neurophysiological, and blood features will enable the prediction of individual responses to SLT and rTMS, facilitating the development of optimized, personalized treatment plans for PPA.