Escitalopram and Language Intervention for Subacute Aphasia

NCT03843463 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: IRB00268564P50DC014664
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 3

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).

Conditions

Aphasia; Stroke

Outcome Measures

Primary Outcomes (1)

• Change in Philadelphia Naming Test short-form accuracy score

  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.

  Baseline, 1 week after computer-delivered naming treatment

Secondary Outcomes (13)

• Language production as assessed by lexical features of discourse in "Cookie Theft" picture description

  Baseline, 5 weeks after computer-delivered naming treatment

• Language production as assessed by content units included in picture description of "Cookie Theft"

  Baseline, 5 weeks after computer-delivered naming treatment

• 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

• Depression as assessed by Patient Health Questionnaire (PHQ-9)

  Baseline, 1 week after computer-delivered naming treatment

• Language production as assessed by Morphosyntactic Generation (MorGen) Test

  Baseline, 1 week after computer-delivered naming treatment

Study Arms (2)

Naming Treatment + Escitalopram

EXPERIMENTAL

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; Behavioral: Computer-delivered naming treatment

Naming Treatment + Placebo

PLACEBO COMPARATOR

10 mg placebo daily for three months

Drug: Placebo; Behavioral: Computer-delivered naming treatment

Interventions

Escitalopram 10mg DRUG

Escitalopram tablet

Also known as: Lexapro

Naming Treatment + Escitalopram

Placebo DRUG

Sugar pill manufactured to mimic escitalopram 10 mg tablet

Also known as: Placebo (for Escitalopram)

Naming Treatment + Placebo

Computer-delivered naming treatment BEHAVIORAL

15 45-minute sessions of computer-delivered naming treatment beginning two months following stroke

Also known as: Computer-delivered naming treatment (CoDeNT)

Naming Treatment + Escitalopram; Naming Treatment + Placebo

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Johns Hopkins University: lead
• University of South Carolina: collaborator
• Medical University of South Carolina: collaborator
• University of California, Irvine: collaborator
• National Institute on Deafness and Other Communication Disorders (NIDCD): collaborator

Study Sites (3)

Johns Hopkins School of Medicine

Baltimore, Maryland, 21287, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

University of South Carolina

Columbia, South Carolina, 29208, United States

RECRUITING

Related Publications (27)

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  PMID: 12649521 BACKGROUND

• Brady MC, Kelly H, Godwin J, Enderby P, Campbell P. Speech and language therapy for aphasia following stroke. Cochrane Database Syst Rev. 2016 Jun 1;2016(6):CD000425. doi: 10.1002/14651858.CD000425.pub4.

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• Chollet F, Tardy J, Albucher JF, Thalamas C, Berard E, Lamy C, Bejot Y, Deltour S, Jaillard A, Niclot P, Guillon B, Moulin T, Marque P, Pariente J, Arnaud C, Loubinoux I. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. Lancet Neurol. 2011 Feb;10(2):123-30. doi: 10.1016/S1474-4422(10)70314-8. Epub 2011 Jan 7.

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• FOCUS Trial Collaboration. Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial. Lancet. 2019 Jan 19;393(10168):265-274. doi: 10.1016/S0140-6736(18)32823-X. Epub 2018 Dec 5.

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• Doron R, Lotan D, Versano Z, Benatav L, Franko M, Armoza S, Kately N, Rehavi M. Escitalopram or novel herbal mixture treatments during or following exposure to stress reduce anxiety-like behavior through corticosterone and BDNF modifications. PLoS One. 2014 Apr 1;9(4):e91455. doi: 10.1371/journal.pone.0091455. eCollection 2014.

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• Enderby P, Broeckx J, Hospers W, Schildermans F, Deberdt W. Effect of piracetam on recovery and rehabilitation after stroke: a double-blind, placebo-controlled study. Clin Neuropharmacol. 1994 Aug;17(4):320-31. doi: 10.1097/00002826-199408000-00003.

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• Fridriksson J, Elm J, Stark BC, Basilakos A, Rorden C, Sen S, George MS, Gottfried M, Bonilha L. BDNF genotype and tDCS interaction in aphasia treatment. Brain Stimul. 2018 Nov-Dec;11(6):1276-1281. doi: 10.1016/j.brs.2018.08.009. Epub 2018 Aug 18.

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• Gu SC, Wang CD. Early Selective Serotonin Reuptake Inhibitors for Recovery after Stroke: A Meta-Analysis and Trial Sequential Analysis. J Stroke Cerebrovasc Dis. 2018 May;27(5):1178-1189. doi: 10.1016/j.jstrokecerebrovasdis.2017.11.031. Epub 2017 Dec 21.

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• Hayasaka Y, Purgato M, Magni LR, Ogawa Y, Takeshima N, Cipriani A, Barbui C, Leucht S, Furukawa TA. Dose equivalents of antidepressants: Evidence-based recommendations from randomized controlled trials. J Affect Disord. 2015 Jul 15;180:179-84. doi: 10.1016/j.jad.2015.03.021. Epub 2015 Mar 31.

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• Hillis AE. The 'standard' for poststroke aphasia recovery. Stroke. 2010 Jul;41(7):1316-7. doi: 10.1161/STROKEAHA.110.585364. Epub 2010 Jun 10. No abstract available.

  PMID: 20538691 BACKGROUND

• Hillis AE, Beh YY, Sebastian R, Breining B, Tippett DC, Wright A, Saxena S, Rorden C, Bonilha L, Basilakos A, Yourganov G, Fridriksson J. Predicting recovery in acute poststroke aphasia. Ann Neurol. 2018 Mar;83(3):612-622. doi: 10.1002/ana.25184. Epub 2018 Mar 10.

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• Hillis AE, Tippett DC. Stroke Recovery: Surprising Influences and Residual Consequences. Adv Med. 2014;2014:378263. doi: 10.1155/2014/378263.

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• Huber W, Willmes K, Poeck K, Van Vleymen B, Deberdt W. Piracetam as an adjuvant to language therapy for aphasia: a randomized double-blind placebo-controlled pilot study. Arch Phys Med Rehabil. 1997 Mar;78(3):245-50. doi: 10.1016/s0003-9993(97)90028-9.

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• Jorge RE, Acion L, Moser D, Adams HP Jr, Robinson RG. Escitalopram and enhancement of cognitive recovery following stroke. Arch Gen Psychiatry. 2010 Feb;67(2):187-96. doi: 10.1001/archgenpsychiatry.2009.185.

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• Kraglund KL, Mortensen JK, Damsbo AG, Modrau B, Simonsen SA, Iversen HK, Madsen M, Grove EL, Johnsen SP, Andersen G. Neuroregeneration and Vascular Protection by Citalopram in Acute Ischemic Stroke (TALOS). Stroke. 2018 Nov;49(11):2568-2576. doi: 10.1161/STROKEAHA.117.020067.

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• Kurland J, Pulvermuller F, Silva N, Burke K, Andrianopoulos M. Constrained versus unconstrained intensive language therapy in two individuals with chronic, moderate-to-severe aphasia and apraxia of speech: behavioral and fMRI outcomes. Am J Speech Lang Pathol. 2012 May;21(2):S65-87. doi: 10.1044/1058-0360(2012/11-0113). Epub 2012 Jan 31.

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• Lam RW. Antidepressants and QTc prolongation. J Psychiatry Neurosci. 2013 Mar;38(2):E5-6. doi: 10.1503/jpn.120256. No abstract available.

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• Lazar RM, Minzer B, Antoniello D, Festa JR, Krakauer JW, Marshall RS. Improvement in aphasia scores after stroke is well predicted by initial severity. Stroke. 2010 Jul;41(7):1485-8. doi: 10.1161/STROKEAHA.109.577338. Epub 2010 Jun 10.

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• Marangolo P, Fiori V, Sabatini U, De Pasquale G, Razzano C, Caltagirone C, Gili T. Bilateral Transcranial Direct Current Stimulation Language Treatment Enhances Functional Connectivity in the Left Hemisphere: Preliminary Data from Aphasia. J Cogn Neurosci. 2016 May;28(5):724-38. doi: 10.1162/jocn_a_00927. Epub 2016 Jan 25.

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  BACKGROUND

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• Stockbridge MD, Fridriksson J, Sen S, Bonilha L, Hillis AE. Protocol for Escitalopram and Language Intervention for Subacute Aphasia (ELISA): A randomized, double blind, placebo-controlled trial. PLoS One. 2021 Dec 23;16(12):e0261474. doi: 10.1371/journal.pone.0261474. eCollection 2021.

  PMID: 34941929 DERIVED

MeSH Terms

Conditions

Aphasia; Stroke

Interventions

Escitalopram

Condition Hierarchy (Ancestors)

Speech Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Argye Hillis-Trupe, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Argye Hillis-Trupe, MD

CONTACT

(410) 614-2381; argye@jhmi.edu

Melissa D Stockbridge, PhD

CONTACT

md.stockbridge@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2019
• First Posted: February 18, 2019
• Study Start: July 18, 2021
• Primary Completion (Estimated): September 18, 2026
• Study Completion (Estimated): January 18, 2027
• Last Updated: September 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)