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Brain Correlates of Multimodal Rehabilitation in Chronic Post-stroke Aphasia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04134416
Recruitment Status : Recruiting
First Posted : October 22, 2019
Last Update Posted : November 1, 2019
Sponsor:
Information provided by (Responsible Party):
Marcelo Luis Berthier, University of Malaga

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.

Condition or disease Intervention/treatment Phase
Aphasia Stroke Drug: Donepezil Behavioral: Intensive-Language Action Therapy Device: Transcranial direct current stimulation Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: This is an open label except for the tCDS treatment which is double blind (AtDCS vs shamtDCS).
Primary Purpose: Treatment
Official Title: Effects of Combining Donepezil, Intensive Language Rehabilitation and Transcranial Direct Current Stimulation on Language Recovery and Brain Reorganization in Chronic Post-stroke Aphasia
Actual Study Start Date : January 8, 2019
Estimated Primary Completion Date : July 20, 2020
Estimated Study Completion Date : July 20, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Anodal transcranial direct current stimulation
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
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).

Behavioral: Intensive-Language Action Therapy
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.

Device: Transcranial direct current stimulation
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.

Sham Comparator: Sham transcranial direct current stimulation
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
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).

Behavioral: Intensive-Language Action Therapy
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.

Device: Transcranial direct current stimulation
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.




Primary Outcome Measures :
  1. Western Aphasia Battery (WAB) [ Time Frame: Each participant will be evaluated at week 0 (baseline), 8, 10 and 26. ]

    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.


  2. Communicative Activity Log (CAL) [ Time Frame: Each participant/ main carer will be evaluated at week 0 (baseline), 8, 10 and 26. ]
    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.

  3. Stroke Aphasia Depression Questionnaire (SADQ-10) [ Time Frame: Each participant/ main carer will be evaluated at week 0 (baseline), 8, 10 and 26. ]
    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.

  4. Stroke and Aphasia Quality of Life Scale 39 (SAQOL-39) [ Time Frame: Each participant/ main carer will be evaluated at week 0 (baseline), 8, 10 and 26. ]

    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.



Secondary Outcome Measures :
  1. Mini Mental State Examination (MMSE) [ Time Frame: Each participant will be evaluated at week 0 (baseline). ]
    To assess cognitive impairment in persons with post-stroke aphasia. Minimum and maximum scores: 1-30 points. Higher values mean better outcome.

  2. Trail-Making Test, parts A & B (TMT) [ Time Frame: Each participant will be evaluated at week 0 (baseline), 8, 10 and 26. ]
    To assess executive functions in individuals affected by post-stroke aphasia. Changes from Baseline in TMT scores at 8, 10 and 26 weeks. The participant has to finish both parts as quickly as possible, with the time taken to complete the test being used as the primary performance metric. Lower completion time means better outcome.

  3. Digit Span Test from the Wechsler Adult Intelligence Scale (WAIS) [ Time Frame: Each participant will be evaluated at week 0 (baseline), 8, 10 and 26. ]
    To assess immediate memory in persons with post-stroke aphasia. Changes from Baseline in Digit scores at 8, 10 and 26 weeks. Minimum and maximum scores: 3-9. Higher values mean better outcome.

  4. Attention Network Test (ANT). [ Time Frame: Each participant will be evaluated at week 0 (baseline), 8, 10 and 26. ]

    To assess three attentional networks: alerting, orienting, and executive control in in persons with post-stroke aphasia.

    Changes from Baseline in ANT scores at 8, 10 and 26 weeks. Efficiency of the alerting network is examined by changes in Reaction Time (RT) resulting from a warning signal. Efficiency of orienting is examined by changes in RT that accompany cues indicating where the target will occur. The efficiency of the executive network is examined by requiring the subject to respond by pressing two keys indicating the direction (left or right) of a central arrow surrounded by congruent, incongruent or neutral flankers.

    Lower reaction time and higher congruent responses mean better outcome.


  5. Raven´s Colored Progressive Matrices (RPM), set A, B & AB [ Time Frame: Each participant will be evaluated at week 0 (baseline). ]
    To assess abstract reasoning in persons with post-stroke aphasia. Evaluation at baseline. Minimum and maximum score: 0-36. Higher scores mean better outcome.

  6. Cognitive Reserve Questionnaire. [ Time Frame: Each participant will be evaluated at week 0 (baseline) ]
    To assess the cognitive reserve of persons with post-stroke aphasia. Evaluation at baseline. Minimum and maximum scores: 0-25. Higher values mean better outcome.

  7. Hospital Anxiety and Depression Scale (HADS). [ Time Frame: Each participant/ main carer will be evaluated at week 0 (baseline), 8, 10 and 26. ]

    To assess depressive and anxious symptomatology in persons with post-stroke aphasia.

    Changes from Baseline in HADS scores at 8, 10 and 26 weeks. Minimum and maximum scores: 0-21 points (Anxiety scale); 0-21 points (Depression scale). Lower values mean better outcome.


  8. Visual Dynamic Analogue Scale (D-VAMS). [ Time Frame: Each participant will be evaluated at week 0 (baseline), 8, 10 and 26. ]
    To assess mood in persons with post-stroke aphasia. Changes from Baseline in D-VAMS scores at 8, 10 and 26 weeks. Minimum and maximum score: 0-100 points. Higher values mean better outcome.

  9. Neuropsychiatric Inventory (NPI). [ Time Frame: Each participant/ main carer will be evaluated at week 0 (baseline), 8, 10 and 26. ]
    To assess neuropsychiatric symptomatology in persons with post-stroke aphasia. Changes from Baseline in NPI scores at 8, 10 and 26 weeks. Minimum and maximum scores: 0-12 points for each subscale. Score obtained by multiplying frequency*severity scores. No total score available. Lower values mean better outcome.

  10. Starkstein Apathy Scale (SAS). [ Time Frame: Each participant/ main carer will be evaluated at week 0 (baseline), 8, 10 and 26. ]
    To assess apathy in persons with post-stroke aphasia. Changes from Baseline in SAS scores at 8, 10 and 26 weeks. Minimum and maximum scores: 0-42 points. Lower values mean better outcome.

  11. Catastrophic Reaction Scale (CRS) [ Time Frame: Each participant/ main carer will be evaluated at week 0 (baseline), 8, 10 and 26. ]
    To assess catastrophic reactions in persons with post-stroke aphasia. Changes from Baseline in CRS scores at 8, 10 and 26 weeks. Minimum and maximum scores: 0-33 points. Lower values mean better outcome.

  12. Neurobehavioral Change after Aphasia Scale (experimental test). [ Time Frame: Each participant/ main carer will be evaluated at week 0 (baseline), 8, 10 and 26. ]
    To assess personality changes in persons with post-stroke. Changes from Baseline scores at 8, 10 and 26 weeks. Minimum and maximum scores: 1-7 points for each subscale. Higher values mean better outcome.

  13. Barthel Index (IB) [ Time Frame: Each participant/ main carer will be evaluated at week 0 (baseline), 8, 10 and 26. ]
    To assess functional independence in persons with post-stroke aphasia. Changes from Baseline in functional independence scores at 8, 10 and 26 weeks. Minimum and maximum scores: 0-100 points. Higher values mean better outcome.

  14. Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) [ Time Frame: Each participant/ main carer will be evaluated at week 0 (baseline), 8, 10 and 26. ]
    To rule out dementia in persons with post-stroke aphasia. Changes from Baseline in functional independence scores at 8, 10 and 26 weeks. Minimum and maximum scores: 26-130 points. Lower values mean better outcome.

  15. Visual-analogue test assessing anosognosia for language impairment (VATA-L) [ Time Frame: Each participant/ main carer will be evaluated at week 0 (baseline), 8, 10 and 26 ]
    To screen for anosognosia for aphasia in persons with post-stroke aphasia. Changes from Baseline in anosognosia scores at 8,10 and 26 weeks. Minimum and maximum scores: 0-42. Lower values mean better outcome.

  16. Communicative Effectiveness Index (CETI) [ Time Frame: Each participant/ main carer will be evaluated at week 0 (baseline), 8, 10 and 26. ]
    To assess functional communication in persons with post-stroke aphasia. Changes from Baseline in functional communication scores at 8, 10 and 26 weeks. Minimum and maximum scores: 0-100. Higher values mean better outcome.

  17. The Apraxia of Speech Rating Scale (ASRS). [ Time Frame: Each participant will be evaluated at week 0 (baseline), 8, 10 and 26. ]

    To assess and quantify the presence or absence, relative frequency, and severity of To rate apraxia of speech and its main characteristics in persons with post-stroke aphasia.

    Minimum and maximum scores: 0-4 points for each subscale. Lower values mean better outcome.


  18. Corsi Block Tapping Test from the Wechsler Adult Intelligence Scale (WAIS) [ Time Frame: Each participant will be evaluated at week 0 (baseline), 8, 10 and 26. ]
    To assess visuo-spatial working memory in persons with post-stroke aphasia. Changes from Baseline in visual working memory scores at 8,10 and 26 weeks. Minimum and maximum scores: 3-9. Higher values mean better outcome.

  19. Batería para la Evaluación de los Trastornos Afásicos (BETA). Battery for the Evaluation of Aphasia Disorders. Subscale 1,2,6,13,14,21 & 26. [ Time Frame: Each participant will be evaluated at week 0 (baseline), 8, 10 and 26. ]
    To assess linguistic abilities in persons with post-stroke aphasia. Subscales: 1,2,6,13,14,21 & 26 Changes from Baseline in linguistic abilities scores at 8,10 and 26 weeks. Minimum and maximum scores: 1-30. Higher values mean better outcome.

  20. Queens List for the Repetition of Stimuli (experimental test) [ Time Frame: Each participant will be evaluated at week 0 (baseline), 8, 10 and 26. ]

    To assess linguistic abilities (repetition/naming) in individuals affected by post-stroke aphasia.

    Changes from Baseline in linguistic abilities scores at 8,10 and 26 weeks. Minimum and maximum scores: 1-48. Higher values mean better outcome.


  21. Repetition of clichés and novel sentences (experimental test) [ Time Frame: Each participant will be evaluated at week 0 (baseline), 8, 10 and 26. ]

    To assess repetition of clichés and novel sentences in persons with post-stroke aphasia.

    Changes from Baseline in linguistic abilities scores at 8,10 and 26 weeks. Minimum and maximum scores: 0-40. Higher values mean better outcome.


  22. Queens List for the Naming of Stimuli (experimental test) [ Time Frame: Each participant will be evaluated at week 0 (baseline), 8, 10 and 26. ]

    To assess linguistic abilities (repetition/naming) in individuals affected by post-stroke aphasia.

    Changes from Baseline in linguistic abilities scores at 8,10 and 26 weeks. Minimum and maximum scores: 1-48. Higher values mean better outcome.


  23. Non-Verbal Oral Apraxia Screening Test (experimental test) [ Time Frame: Each participant will be evaluated at week 0 (baseline), 8, 10 and 26. ]

    To assess non-verbal oral apraxia in individuals affected by post-stroke aphasia.

    Changes from Baseline (week 0) in oral apraxia scores at 8,10 and 26 weeks. Minimum and maximum scores: 0-32. Higher values mean better outcome.


  24. Cognition test for Patients with Aphasia (experimental test) [ Time Frame: Each participant will be evaluated at week 0 (baseline). ]
    To assess cognitive impairment in persons with post-stroke aphasia. Minimum and maximum scores: 1-30 points. Higher values mean better outcome.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04134416


Contacts
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Contact: Marcelo L. Berthier, MD, PhD 0034 952137607 mbt@uma.es
Contact: Guadalupe Dávila, PhD 0034 952137607 mgdavila@uma.es

Locations
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Spain
Centro de Investigaciones Medico-Sanitarias. University of Malaga Recruiting
Málaga, Spain, 29010
Contact: Marcelo L. Berthier, MD, PhD    0034 952137607    mbt@uma.es   
Contact: Guadalupe Dávila, PhD    0034 952137607    mgdavila@uma.es   
Sponsors and Collaborators
University of Malaga
Investigators
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Principal Investigator: Marcelo L Berthier, MD, PhD University of Malaga, Spain
Additional Information:
Publications:

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Responsible Party: Marcelo Luis Berthier, Full Professor, University of Malaga
ClinicalTrials.gov Identifier: NCT04134416    
Other Study ID Numbers: FIM-DON-2017-01
First Posted: October 22, 2019    Key Record Dates
Last Update Posted: November 1, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Marcelo Luis Berthier, University of Malaga:
Aphasia
Stroke
Rehabilitation
Non-invasive brain stimulation
Cognitive enhancing drug
Intensive Language-Action Therapy
Additional relevant MeSH terms:
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Stroke
Aphasia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Donepezil
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents