Brain Correlates of Multimodal Rehabilitation in Chronic Post-stroke Aphasia

NCT04134416 | Completed Phase 3 DMC

• 1 other identifier: FIM-DON-2017-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Post-stroke aphasia (PSA), the partial or total loss of the ability to produce and/or understand language associated with stroke, is a highly prevalent and disabling disorder that negatively impacts the personal, social and working life of patients and families. Modern theory-based language therapies (LT) with proved efficacy in chronic PSA are brief (weeks), intensive, and oriented to specific domains (e.g., anomia). However, in order to maximize therapeutic benefits, it becomes essential to implement complementary strategies that boost gains in language, communication and behaviour and also to identify predictors of treatment response (demographics, anatomical) that enable to customize interventions adjusting them to each profile (linguistic deficits, brain structure and connectivity). Our group has repeatedly shown that LT combined with cognitive enhancing drugs (CED) (e.g., Donepezil and Memantine) are safe and promote better outcomes that when these interventions are administered separately. Moreover, non-invasive brain stimulation techniques (NIBS), such as transcranial direct current stimulation (tDCS), are also emerging as a promising treatment option for chronic PSA. However, is still unknown whether or not treatments that combine several biological strategies aid to improve outcomes further. Brain changes induced by these interventions and the premorbid characteristic of a "good responder" are also unknown. The aims of this clinical trial are: (1) Study the efficacy of combined treatments in a sample of patients with chronic PSA (n = 40); (2) Document with multimodal neuroimaging the functional and connectivity changes (neuroplasticity) promoted by these interventions; and (3) Identify linguistic, cognitive and behavioural variables that may predict outcomes for each intervention.

Conditions

Aphasia; Stroke

Keywords

Aphasia; Stroke; Rehabilitation; Non-invasive brain stimulation; Cognitive enhancing drug; Intensive Language-Action Therapy

Outcome Measures

Primary Outcomes (4)

• Western Aphasia Battery (WAB)

  To assess major clinical aspects of language function: information content, fluency, auditory comprehension, repetition and naming. Changes from Baseline in Western Aphasia Battery scores at 8, 10 and 26 weeks. Minimum and maximum values: 0-100 points. Higher scores mean better outcome.

  Each participant will be evaluated at week 0 (baseline), 8, 10 and 26.

• Communicative Activity Log (CAL)

  To assess communicative behavior in the everyday life of patients. Changes from Baseline in CAL scores at 8, 10 and 26 weeks. Minimum and maximum values: 0-90 points (0-40 points for quality of communication; 0-40 points for amount of communication). Higher values mean better outcome.

  Each participant/ main carer will be evaluated at week 0 (baseline), 8, 10 and 26.

• Stroke Aphasia Depression Questionnaire (SADQ-10)

  To assess depressive symptomatology in persons with post-stroke aphasia. Changes from Baseline in SADQ-10 scores at 8, 10 and 26 weeks. Minimum and maximum scores: 1-30 points. Lower values mean better outcome.

  Each participant/ main carer will be evaluated at week 0 (baseline), 8, 10 and 26.

• Stroke and Aphasia Quality of Life Scale 39 (SAQOL-39)

  To assess Quality of Life in persons with post-stroke aphasia. Changes from Baseline in SAQOL-39 scores at 8, 10 and 26 weeks. Minimum and maximum scores: 1-85 (Physical scale); 1-35 (Communication scale); 1-55 (Psychosocial scale); 1-20 (Vitality scale); 1-5 (Total mean scale). Higher values mean better outcome.

  Each participant/ main carer will be evaluated at week 0 (baseline), 8, 10 and 26.

Secondary Outcomes (24)

• Mini Mental State Examination (MMSE)

  Each participant will be evaluated at week 0 (baseline).

• Trail-Making Test, parts A & B (TMT)

  Each participant will be evaluated at week 0 (baseline), 8, 10 and 26.

• Digit Span Test from the Wechsler Adult Intelligence Scale (WAIS)

  Each participant will be evaluated at week 0 (baseline), 8, 10 and 26.

• Attention Network Test (ANT).

  Each participant will be evaluated at week 0 (baseline), 8, 10 and 26.

• Raven´s Colored Progressive Matrices (RPM), set A, B & AB

  Each participant will be evaluated at week 0 (baseline).

Study Arms (2)

Anodal transcranial direct current stimulation

EXPERIMENTAL

Transcortical direct current stimulation (tDCS) will be applied using a STARSTIM neurostimulation device (Neuroelectrics, Barcelona). Each participant will receive 10 20-minute sessions while receiving REGIAplus (online). Group 1 will receive active stimulation (anodal stimulation, A-tDCS).The active electrode will be placed in the region of the lower right frontal rotation and the reference electrode in the extraencephalic zone (left clavicle). Combined rehabilitation sessions (REGIAplus/tDCS) will be conducted, as indicated above, in weeks 9 and 10 of the trial.

Drug: Donepezil; Behavioral: Intensive-Language Action Therapy; Device: Transcranial direct current stimulation

Sham transcranial direct current stimulation

SHAM COMPARATOR

Group 2 will receive sham stimulation (S-tDCS). In the sham stimulation, the same helmet and electrode that is used in the active stimulation will be placed but, in this case, we will apply only a slight current at the beginning and end of the session with the objective of simulating the effects that are experienced with the active stimulation without producing significant cortical stimulation. The active electrode will be placed in the region of the lower right frontal rotation and the reference electrode in the extraencephalic zone (left clavicle). Combined rehabilitation sessions (REGIAplus/tDCS) will be conducted, as indicated above, in weeks 9 and 10 of the assay.

Drug: Donepezil; Behavioral: Intensive-Language Action Therapy; Device: Transcranial direct current stimulation

Interventions

Donepezil DRUG

Donepezil shall be administered at the times stipulated in the study design as follows: one 5 mg tablet at night for 4 weeks and then one 10 mg tablet at night until the end of the trial (week 10).

Anodal transcranial direct current stimulation; Sham transcranial direct current stimulation

Intensive-Language Action Therapy BEHAVIORAL

All patients participating in the study will receive in weeks 9 and 10 daily three and a half hours of ILATplus therapy. This therapy consists of 30 minutes of specific repetition training (tailored and reinforced by the therapist) before starting with classic ILAT for 3 hours/day during 10 consecutive days.

Anodal transcranial direct current stimulation; Sham transcranial direct current stimulation

Transcranial direct current stimulation DEVICE

Transcortical direct current stimulation (tDCS) will be applied using a STARSTIM neurostimulation device (Neuroelectrics, Barcelona). Each participant will receive either anodal or sham 20-minute sessions while receiving ILATplus. In the sham stimulation, the same helmet and electrode that is used in the active stimulation will be placed but, in this case, we will apply only a slight current at the beginning and end of the session with the objective of simulating the effects that are experienced with the active stimulation without producing significant cortical stimulation. The active electrode will be placed in the region of the lower right frontal rotation and the reference electrode in the extraencephalic zone (left clavicle). Combined rehabilitation sessions (ILATplus/tDCS) will be conducted, as indicated above, in weeks 9 and 10 of the trial.

Anodal transcranial direct current stimulation; Sham transcranial direct current stimulation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 70 years
• Right handedness (80 point in the Edinburgh Handedness Inventory)
• Spanish as native language
• Single left-hemisphere stroke
• Diagnosis of aphasia established by a score in the Aphasia Quotient of the Spanish version of the Western Aphasia Battery (WAB) \< 93.8 points.

You may not qualify if:

• Dysarthria without aphasia
• Multiple or bilateral injuries
• Increased risk of a new stroke or unstable neurological condition (e.g. transient ischemic attacks)
• History of severe psychiatric illness (schizophrenia, major depression, bipolar disorder, anxiety disorders)
• Alcohol and substance use or abuse
• Coexistence of aphasia with dementia.

Sponsors & Collaborators

• University of Malaga: lead

Study Sites (1)

Centro de Investigaciones Medico-Sanitarias. University of Malaga

Málaga, 29010, Spain

Location

Related Publications (13)

• Berthier ML. Poststroke aphasia : epidemiology, pathophysiology and treatment. Drugs Aging. 2005;22(2):163-82. doi: 10.2165/00002512-200522020-00006.

  PMID: 15733022 BACKGROUND

• Berthier ML, Garcia-Casares N, Walsh SF, Nabrozidis A, Ruiz de Mier RJ, Green C, Davila G, Gutierrez A, Pulvermuller F. Recovery from post-stroke aphasia: lessons from brain imaging and implications for rehabilitation and biological treatments. Discov Med. 2011 Oct;12(65):275-89.

  PMID: 22031666 BACKGROUND

• Pulvermuller F, Berthier ML. Aphasia therapy on a neuroscience basis. Aphasiology. 2008 Jun;22(6):563-599. doi: 10.1080/02687030701612213. Epub 2008 May 21.

  PMID: 18923644 BACKGROUND

• Berthier ML, Pulvermuller F. Neuroscience insights improve neurorehabilitation of poststroke aphasia. Nat Rev Neurol. 2011 Feb;7(2):86-97. doi: 10.1038/nrneurol.2010.201.

  PMID: 21297651 BACKGROUND

• Berthier ML, Pulvermuller F, Davila G, Casares NG, Gutierrez A. Drug therapy of post-stroke aphasia: a review of current evidence. Neuropsychol Rev. 2011 Sep;21(3):302-17. doi: 10.1007/s11065-011-9177-7. Epub 2011 Aug 16.

  PMID: 21845354 BACKGROUND

• Berthier ML, Green C, Higueras C, Fernandez I, Hinojosa J, Martin MC. A randomized, placebo-controlled study of donepezil in poststroke aphasia. Neurology. 2006 Nov 14;67(9):1687-9. doi: 10.1212/01.wnl.0000242626.69666.e2.

  PMID: 17101908 BACKGROUND

• Berthier ML, Green C, Lara JP, Higueras C, Barbancho MA, Davila G, Pulvermuller F. Memantine and constraint-induced aphasia therapy in chronic poststroke aphasia. Ann Neurol. 2009 May;65(5):577-85. doi: 10.1002/ana.21597.

  PMID: 19475666 BACKGROUND

• De-Torres I, Davila G, Berthier ML, Walsh SF, Moreno-Torres I, Ruiz-Cruces R. Repeating with the right hemisphere: reduced interactions between phonological and lexical-semantic systems in crossed aphasia? Front Hum Neurosci. 2013 Oct 18;7:675. doi: 10.3389/fnhum.2013.00675. eCollection 2013.

  PMID: 24151460 BACKGROUND

• Torres-Prioris MJ, Lopez-Barroso D, Paredes-Pacheco J, Roe-Vellve N, Dawid-Milner MS, Berthier ML. Language as a Threat: Multimodal Evaluation and Interventions for Overwhelming Linguistic Anxiety in Severe Aphasia. Front Psychol. 2019 May 8;10:678. doi: 10.3389/fpsyg.2019.00678. eCollection 2019.

  PMID: 31133908 BACKGROUND

• Mohr B, Stahl B, Berthier ML, Pulvermuller F. Intensive Communicative Therapy Reduces Symptoms of Depression in Chronic Nonfluent Aphasia. Neurorehabil Neural Repair. 2017 Dec;31(12):1053-1062. doi: 10.1177/1545968317744275. Epub 2017 Dec 1.

  PMID: 29192534 BACKGROUND

• Berthier ML, De-Torres I, Paredes-Pacheco J, Roe-Vellve N, Thurnhofer-Hemsi K, Torres-Prioris MJ, Alfaro F, Moreno-Torres I, Lopez-Barroso D, Davila G. Cholinergic Potentiation and Audiovisual Repetition-Imitation Therapy Improve Speech Production and Communication Deficits in a Person with Crossed Aphasia by Inducing Structural Plasticity in White Matter Tracts. Front Hum Neurosci. 2017 Jun 14;11:304. doi: 10.3389/fnhum.2017.00304. eCollection 2017.

  PMID: 28659776 BACKGROUND

• Barbancho MA, Berthier ML, Navas-Sanchez P, Davila G, Green-Heredia C, Garcia-Alberca JM, Ruiz-Cruces R, Lopez-Gonzalez MV, Dawid-Milner MS, Pulvermuller F, Lara JP. Bilateral brain reorganization with memantine and constraint-induced aphasia therapy in chronic post-stroke aphasia: An ERP study. Brain Lang. 2015 Jun-Jul;145-146:1-10. doi: 10.1016/j.bandl.2015.04.003. Epub 2015 Apr 29.

  PMID: 25932618 BACKGROUND

• Edelkraut L, Lopez-Barroso D, Torres-Prioris MJ, Starkstein SE, Jorge RE, Aloisi J, Berthier ML, Davila G. Spectrum of neuropsychiatric symptoms in chronic post-stroke aphasia. World J Psychiatry. 2022 Mar 19;12(3):450-469. doi: 10.5498/wjp.v12.i3.450. eCollection 2022 Mar 19.

  PMID: 35433325 DERIVED

Related Links

• webiste of the university of Malaga, Spain

MeSH Terms

Conditions

Aphasia; Stroke

Interventions

Donepezil; Transcranial Direct Current Stimulation

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)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Officials

• Marcelo L Berthier, MD, PhD

  University of Malaga, Spain

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is an open label except for the tCDS treatment which is double blind (AtDCS vs shamtDCS).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Study Record Dates

• First Submitted: October 16, 2019
• First Posted: October 22, 2019
• Study Start: January 8, 2019
• Primary Completion: October 20, 2020
• Study Completion: October 20, 2020
• Last Updated: November 5, 2020

Record last verified: 2020-11

Locations

ES (1)