Clinical trial NCT05179538: Genetic and Cognitive Predictors of Aphasia Treatment Response
Official title: Laying the Groundwork for Personalized Medicine in Aphasia Therapy: Genetic and Cognitive Predictors of Restorative Treatment Response
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Aphasia
Lead sponsor: Ohio State University
Sponsor class: OTHER
Collaborators: name: Nationwide Children's Hospital
First posted: 2022-01-05
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: There will be four subgroups based on the expression of BDNF and ApoE.
Primary purpose: TREATMENT

Brief summary: Aphasia, or language impairment after a stroke, affects approximately 2 million people in the United States, with an estimated 180,000 new cases each year. The medical community cannot predict how well someone with aphasia will respond to treatment, as some people with aphasia are poor responders to intervention even when participating in empirically supported treatments. There is a strong likelihood that genetics play a role in language recovery after stroke, but very little research has been dedicated to investigating this link. This study will investigate whether two genes and cognitive abilities, such as memory, predict responsiveness to aphasia therapy for word-retrieval difficulties.

Detailed description: Incomplete understanding of patient-specific factors that determine whether someone will respond well to language therapy after stroke limits the development of methods to target or account for sources of variability. There is a strong likelihood that genetics play a role in language recovery after stroke, but very little research has been dedicated to investigating this link. The long-term goal of this line of work is to maximize response to aphasia therapy by incorporating patient-specific factors into decisions related to treatment planning. The overall objective of this application is to identify patterns of patient-specific factors including two candidate genes and cognitive skills that show a relationship with treatment outcomes. The central hypothesis is that there will be a relationship between ApoE and BDNF genotypes, and working memory on stimulus generalization. The rationale for the proposed project is that the identification of factors that impact treatment responsiveness will allow for better estimation of prognosis, improved triage of individuals into appropriate therapy regimens and direct targeting of cognitive factors to maximize behavioral gains. The two specific aims of the project are to determine the degree to which (1) ApoE and BDNF genotypes influence how individuals with aphasia respond to therapy, and (2) working memory abilities are related to stimulus acquisition and stimulus generalization after anomia therapy. Individuals with chronic post-stroke aphasia will undergo cognitive and language assessment, and provide a saliva sample for genetic analysis prior to participating in a cued picture-naming therapy for anomia. The expected outcomes are to integrate cognitive scores and genotypes for BDNF and ApoE into formulating probabilities of individual patient responsiveness to restorative therapy. Improvement in word retrieval abilities will be evaluated using the percentage of pictures named correctly. This contribution is expected to be significant because it will allow for more informed clinical decision making and better allocation of resources to appropriate treatments, thereby making advances in the field toward more personalized medicine, as opposed to a one-size-fits-all clinical approach.

The investigators will determine genotypes for BDNF and ApoE, which will yield four separate groups. At least 20 participants will be enrolled for each genotype group.

Eligibility criteria: Inclusion Criteria:

* At least six months post-onset of a single left-hemisphere stroke
* Chronic aphasia
* Anomia (word-retrieval deficits)
* Native English Speaker.

Exclusion Criteria:

* Severe motor speech disorders
* Severe auditory comprehension deficits
* Severe depression.
* Diffuse injury or disease of the brain
* Uncorrected vision or hearing difficulties
* Contraindications for MRI (e.g. cardiac pacemaker, ferrous metal implants, claustrophobia, pregnancy).

Primary outcomes:
measure: Percent of pictures named correctly
timeFrame: from baseline to 1 month
measure: Percentage of pictures named correctly
timeFrame: 4 months
Secondary outcomes:
measure: percentage of definitions named correctly
timeFrame: after 1 month
measure: Percentage of untrained pictures named correctly
timeFrame: after 1 month
Other outcomes:
Locations:
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
Study officials:
affiliation: Ohio State University
name: Stacy M Harnish, PhD
role: PRINCIPAL_INVESTIGATOR
References: