Clinical trial NCT06471127: Neuroplasticity Biomarkers in Aphasia
Official title: Genetic and MRI Biomarkers of Neuroplasticity Predict Aphasia Recovery and Phenotypes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Aphasia
Language
Stroke
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute on Deafness and Other Communication Disorders (NIDCD)
First posted: 2024-06-24
Enrollment: 90
Sex: ALL
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Translational. This protocol 1) tests neural mechanisms of connectivity and reorganization that support post-stroke language recovery and 2) determines biomarkers predictive of language impairments to improve prognostics for persons with aphasia.
Primary purpose: OTHER

Brief summary: Patients with stroke frequently suffer from aphasia, a disorder of expressive and/or receptive language, that can lead to serious health consequences, including social isolation, depression, reduced quality of life, and increased caregiver burden. Aphasia recovery varies greatly between individuals, and likely relies upon the capacity for neuroplasticity, both at a systems level of reorganized brain networks and a molecular level of neuronal repair and plasticity. The proposed work will evaluate genetic and neural network biological markers of neuroplasticity associated with variability in aphasia, with a future goal to improve prognostics and identify therapeutic targets to reduce the long-term burdens of aphasia.

Detailed description: Aphasia is an acquired neurologic language disorder that is among the most challenging long-term disabilities for stroke survivors, often leading to social isolation and reduced quality of life. Recovery from aphasia relies on plasticity in residual brain networks. However, neuroplasticity varies substantially across individuals, making the presence, severity, and phenotype of language impairments challenging to predict. A vital step toward post-stroke precision medicine is identifying neuroplasticity-related biological markers that can improve prognostic models and targeted neurorehabilitation therapies for people with aphasia. The proposed research will test the central hypothesis that individual differences in neuroplasticity, measured through genetic polymorphisms and longitudinal neuroimaging connectivity biomarkers, will account for significant variance in post-stroke aphasia recovery. This 5-year project will include three specific aims. Aim 1 is to index spontaneous recovery by determining relationships between genetic biomarkers of plasticity, longitudinal neural network connectivity, and changes in language during sub-acute to chronic stroke recovery. Aim 2 is to identify genetic and MRI biomarkers predictive of chronic post-stroke aphasia severity and phenotypes. Aim 3 is to characterize genetic and MRI biomarkers associated with verbal learning variability in chronic aphasia. These data will support the development of a larger, multi-site R01 study to examine interactions between multiple biomarkers of neuroplasticity that inform longitudinal aphasia prognostics and treatment efficacy.

Eligibility criteria: Inclusion Criteria:

1. Ages 40-90
2. Right-handed (prior to stroke)
3. Proficient English speakers
4. History of a single ischemic stroke in the middle cerebral artery territory that is lateralized to the left or right (Aim 1) cerebral hemisphere.
5. Presence of aphasia (Aims 2-3)
6. Capacity to understand the nature of the study and provide informed consent
7. Acute or subacute stroke at the time of Aim 1 enrollment; Stroke #12 months old (chronic) at the time of Aims 2-3 enrollment
8. Medically stable

Exclusion Criteria:

1. History of significant medical or neurological disorder (other than stroke)
2. History of significant or poorly controlled psychiatric disorders
3. Current abuse of alcohol or drugs, prescription or otherwise
4. Clinically significant and uncorrected vision or hearing loss
5. Anything other than standard of care stroke treatment such as Plavix, aspirin (81-300 mg daily), beta-blockers, diabetes medications or choles- terol-lowering agents, thrombolytics (e.g., tPA), anticoagulation agents such as Heparin, Warfarin/Coumadin

Primary outcomes:
measure: Aphasia presence/severity
timeFrame: 3 months, 6 months, 1 year post-stroke
measure: Semantic processing
timeFrame: At least 1 year post-stroke
measure: Phonological processing
timeFrame: At least 1 year post-stroke
measure: Noun processing
timeFrame: At least 1 year post-stroke
measure: Verb processing
timeFrame: At least 1 year post-stroke
measure: Pseudoword learning
timeFrame: At least 1 year post-stroke
measure: Verbal learning
timeFrame: At least 1 year post-stroke
Secondary outcomes:
Other outcomes:
Locations:
city: Madison
country: United States
facility: UW School of Medicine and Public Health
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Haley Dresang, PhD
role: PRINCIPAL_INVESTIGATOR
References: