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ELISA: Escitalopram and Language Intervention for Subacute Aphasia

Sponsor
Johns Hopkins University (Other)
Overall Status
Recruiting
CT.gov ID
NCT03843463
Collaborator
University of South Carolina (Other), Medical University of South Carolina (Other), University of California, Irvine (Other)
88
Enrollment
3
Locations
2
Arms
54
Anticipated Duration (Months)
29.3
Patients Per Site
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In this project, the investigators will investigate the effects of a selective serotonin reuptake inhibitor (SSRI), escitalopram, on augmenting language therapy effectiveness, as measured by naming untrained pictures and describing pictures, in individuals with aphasia in the acute and subacute post stroke period (i.e., within three months post stroke).

Condition or Disease Intervention/Treatment Phase
  • Drug: Escitalopram 10mg
  • Drug: Placebo
  • Behavioral: Computer-delivered naming treatment
 Phase 2

Detailed Description

In this project, the investigators will investigate the effects of a selective serotonin reuptake inhibitor (SSRI), escitalopram, on augmenting language therapy effectiveness, as measured by naming untrained pictures and describing pictures, in individuals with aphasia in the acute and subacute post stroke period (i.e., within three months post stroke). There has been no previous randomized controlled trial (RCT) to evaluate the effect of daily SSRI in the first three months after stroke on improvement of language in people undergoing aphasia treatment. It is plausible that SSRIs, which elevate synaptic serotonin, might enhance recovery by augmenting synaptic plasticity.

The investigators propose to conduct a Phase 2 multi-center, randomized, double blind, placebo-controlled trial of escitalopram for augmenting language intervention in subacute stroke. The investigators hypothesize that daily escitalopram for 90 days after stroke results in greater improvement (compared to placebo) in naming untrained pictures, as well as greater increase in content of picture description and greater improvement in morphosyntactic production, when combined with speech and language treatment (SALT). A second aim is to evaluate the mechanisms of language recovery in individuals who receive active medical treatment and those who receive placebo, using resting state functional magnetic resonance imaging (rsfMRI) and genetic testing. The investigators hypothesize that greater improvement in language is associated with increased connectivity within the left hemisphere language network on rsfMRI in participants who receive escitalopram than in those who receive placebo, independently of improvement in depression. The investigators also hypothesize that the effects are greatest in individuals with val/val allele of brain-derived neurotrophic factor (BDNF) - (consistent with previous studies showing a greater response to treatment and greater neuroplasticity in people with the val/val allele than those with one or more met alleles.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
88 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
Escitalopram and Language Intervention for Subacute Aphasia (ELISA)
Actual Study Start Date :
Jul 18, 2021
Anticipated Primary Completion Date :
Sep 18, 2025
Anticipated Study Completion Date :
Jan 18, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Naming Treatment + Escitalopram

10 mg escitalopram daily for three months (escalating from 5 mg per day for the first week and tapering to 5 mg per day for the last two weeks)

Drug: Escitalopram 10mg
Escitalopram tablet
Other Names:
  • Lexapro

    • Behavioral: Computer-delivered naming treatment
    15 45-minute sessions of computer-delivered naming treatment beginning two months following stroke
    Other Names:
  • CoDeNT (Computer-delivered naming treatment)

    		•
    Placebo Comparator: Naming Treatment + Placebo

    10 mg placebo daily for three months

    Drug: Placebo
    Sugar pill manufactured to mimic escitalopram 10 mg tablet
    Other Names:
  • Placebo (for Escitalopram)

    • Behavioral: Computer-delivered naming treatment
    15 45-minute sessions of computer-delivered naming treatment beginning two months following stroke
    Other Names:
  • CoDeNT (Computer-delivered naming treatment)

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in Philadelphia Naming Test short-form accuracy score [Baseline, 1 week after computer-delivered naming treatment]

      Number of correctly named items of 30 total items on the computerized picture naming assessment. Scores ranges from 0 to 30 with higher scores meaning better naming ability.

    Secondary Outcome Measures

    1. Language production as assessed by lexical features of discourse in "Cookie Theft" picture description [Baseline, 5 weeks after computer-delivered naming treatment]

      Lexical features, meaning carrying units of language (morphemes), will be counted for each Cookie Theft picture description. There is no maximum number of meaning carrying units, but norms are available to assist in the interpretation of this performance.

    2. Language production as assessed by content units included in picture description of "Cookie Theft" [Baseline, 5 weeks after computer-delivered naming treatment]

      Content units are based on a standard scoring template of commonly identified concepts (nouns and verbs) in the left and right regions of the "Cookie Theft" picture. Participants either include or fail to include 30 concepts on the left side of the picture and 23 concepts on the right side of the picture. A ratio of included left content units to included right content units then can be calculated and interpreted as a measure of hemispatial attention.

    3. Language production as assessed by rate of syllables per content unit produced in "Cookie Theft" picture description [Baseline, 5 weeks after computer-delivered naming treatment]

      Syllables included in the picture description are counted. Content units are based on a standard scoring template of commonly identified concepts (nouns and verbs) in the left and right regions of the "Cookie Theft" picture. Participants either include or fail to include 30 concepts on the left side of the picture and 23 concepts on the right side of the picture. The average rate of syllables per content unit produced can then be calculated and interpreted as a measure of efficiency in producing relevant information in the task.

    4. Depression as assessed by Patient Health Questionnaire (PHQ-9) [Baseline, 1 week after computer-delivered naming treatment]

      9 item scale scored 0-3 for each item. PHQ-9 scores of 5, 10, 15, and 20 represent mild, moderate, moderately severe, and severe depression. PHQ-9 >15 or suicidal ideation suggest depression sufficient for exclusion or removal from study.

    5. Language production as assessed by Morphosyntactic Generation (MorGen) Test [Baseline, 1 week after computer-delivered naming treatment]

      60 item assessment of word morphology (e.g., plurals, possessives) and modifiers (e.g., number, size, color). Each item is scored based on produced accurate descriptors of an image relative to a second reference image (e.g., patients see two trees, one larger than the other, and the phrase "little tree" is elicited). Patients are scored for objects correctly named (nouns) out of 60, instances of correct use of plural marker out of 31, instances of correct use of numbers out of 8, instances of correct modifiers denoting size out of 16, instances of correct modifiers denoting color out of 19, instances of correct modifiers denoting possessive markers out of 17, and instances of correctly named possessing individuals (proper names provided on screen) out of 17. These scores can then be interpreted separately or averaged to interpret a broad morphosyntactic accuracy score.

    6. Stroke severity as assessed by NIH Stroke Scale (NIHSS) [Baseline, 5 weeks after computer-delivered naming treatment, 20 weeks after computer-delivered naming treatment]

      The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patient's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items.

    7. Post-stroke level of disability as assessed by modified Rankin Scale (mRS) [Baseline, 1 week after computer-delivered naming treatment]

      The mRS is a 6-level scale from "0-No symptoms" to "6-dead" used to evaluate the degree of disability in patients who have suffered a stroke.

    8. Stroke paresis severity as assessed by right hand strength [Baseline, 1 week after computer-delivered naming treatment]

      Right hand strength assessment by dynamometer

    9. Stroke paresis severity as assessed by right hand dexterity [Baseline, 1 week after computer-delivered naming treatment]

      Right hand dexterity assessment by 9 peg board test

    10. Change in new vocabulary items as assessed by lexical diversity included in story retelling of "Cinderella" [Baseline, 1 week after computer-delivered naming treatment]

      Change in new vocabulary items will be counted for each noun, verb, and adjective in the Cinderella retelling. There is no maximum measure of lexical diversity, but norms are available to assist in the interpretation of this performance.

    11. Change in incidence of new vocabulary items as assessed by lexical diversity included in story retelling of "Cinderella" [Baseline, 1 week after computer-delivered naming treatment]

      Change in incidence of each new item will be counted for each noun, verb, and adjective in the Cinderella retelling. There is no maximum measure of lexical diversity, but norms are available to assist in the interpretation of this performance.

    12. Change in language production as assessed by speech errors produced during the story retelling of "Cinderella" [Baseline, 1 week after computer-delivered naming treatment]

      Change in number of errors will be counted after each retelling is recorded

    13. Change in Language production as assessed by speech pauses produced during the story retelling of "Cinderella" [Baseline, 1 week after computer-delivered naming treatment]

      Change in pauses will be counted after each retelling is recorded

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 99 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Participants must have sustained an acute ischemic left hemisphere stroke.

    • Participants must be fluent speakers of English by self-report.

    • Participants must be capable of giving informed consent or indicating a legally authorized representative to provide informed consent.

    • Participants must be age 18 or older.

    • Participants must be within 5 days of onset of stroke.

    • Participants must be pre-morbidly right-handed by self-report.

    • Participants must have an aphasia diagnosis as confirmed by the Western Aphasia Battery-Revised (Aphasia Quotient < 93.8).

    Exclusion Criteria:

    • Previous neurological disease affecting the brain including previous symptomatic stroke

    • Diagnosis of schizophrenia, autism, or other psychiatric or neurological condition that affects naming/language

    • A history of additional risk factors for torsades de pointes (TdP; e.g., heart failure, hypokalemia, family history of Long QT Syndrome)

    • Current severe depression, defined as a score of > 15 on the Patient Health Questionnaire (PHQ-9)

    • Uncorrected visual loss or hearing loss by self-report

    • Use of any medication approved by the FDA for treatment of depression at the time of stroke onset

    • Concomitant use of any monoamine oxidase inhibitors (MAOIs) or pimozide, or other drugs that prolong the QT/QTc interval, triptans (and other 5-Hydroxytryptamine Receptor Agonists), or other contraindications to escitalopram that may be identified.

    • A QTc greater than 450 milliseconds on electrocardiogram or evidence of hyponatremia (Na < 130) at baseline

    • Pregnancy at the time of stroke or planning to become pregnant during the study term.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Johns Hopkins School of Medicine Baltimore Maryland United States 21287
    2 Medical University of South Carolina Charleston South Carolina United States 29425
    3 University of South Carolina Columbia South Carolina United States 29208

    Sponsors and Collaborators

    • Johns Hopkins University
    • University of South Carolina
    • Medical University of South Carolina
    • University of California, Irvine

    Investigators

    • Principal Investigator: Argye Hillis-Trupe, MD, Johns Hopkins University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Johns Hopkins University
    ClinicalTrials.gov Identifier:
    NCT03843463
    Other Study ID Numbers:
    • IRB00203667
    First Posted:
    Feb 18, 2019
    Last Update Posted:
    Apr 29, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:
    Aphasia
    Dexetimide
    Citalopram

    Study Results

    No Results Posted as of Apr 29, 2022