Brain Mechanisms Underlying Reading Improvement in Central Alexia

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2014 by University College, London
Sponsor:
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT02062619
First received: February 12, 2014
Last updated: NA
Last verified: February 2014
History: No changes posted
  Purpose

Central alexia is a common reading disorder caused by stroke. Patients with central alexia (CA) are slow to read and make frequent errors, and have additional problems with their spoken language.

This study has 3 aims:

  1. Investigating the neural networks that support reading in patients with CA Despite being a relatively common syndrome, there have been no functional brain imaging studies of CA. This project will use magnetic resonance imaging (MRI) and magnetoencephalography (MEG) to understand which brain regions are damaged and whether preserved parts of the reading network can be encouraged by therapy to support reading recovery.
  2. Testing a new treatment for CA The research team has developed training software called 'iReadMore', which uses a crossmodal approach (written words paired with spoken words) to train reading. This therapy has been shown to be effective in patients with a similar form of reading disorder called pure alexia. The iReadMore software will be adapted to address the reading deficit in CA, and the research will test whether it significantly improves reading ability.
  3. Using brain stimulation to enhance behavioural training Transcranial direct current stimulation (tDCS) is a brain stimulation technique that has been shown to improve language performance in healthy controls and stroke patients. This study will test whether tDCS (delivered simultaneously with the 'iReadMore' therapy) significantly enhances reading rehabilitation. Patients will be split into two groups: one will receive a 4 week block of training plus real tDCS first, followed by a 4 week block of training plus sham tDCS; the other group will receive the two therapy blocks in the opposite order. Both groups will ultimately receive the same amount of behavioural therapy and tDCS stimulation. Comparing the reading improvement over the real and sham tDCS blocks will demonstrate whether tDCS enhances the behavioural improvements in reading ability.

Hypothesis:

iReadMore reading therapy will significantly improve single word reading speed in patients with central alexia.

tDCS brain stimulation will significantly enhance the effect of iReadMore therapy, compared to sham stimulation.


Condition Intervention
Stroke
Brain Injuries
Aphasia
Behavioral: Computer-based behavioural word reading therapy
Other: Real tDCS
Other: Sham tDCS

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Brain Mechanisms Underlying Reading Improvement in Central Alexia

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • Change in word reading speed and accuracy for trained and untrained words [ Time Frame: Baseline and up to 3 months follow-up ] [ Designated as safety issue: No ]

    Word reading speed and accuracy will be assessed at multiple time-points:

    T1, T2: baseline assessments.

    T3: following 1 month no training.

    T4: following 1 month of iReadMore training with real / sham tDCS (crossover design).

    T5: following 1 month of iReadMore training with sham / real tDCS (crossover allocation reversed).

    T6: follow-up assessment after 3 months with no training.

    Planned comparisons:

    T3 vs [average of T1 and T2]: spontaneous improvement in reading ability

    T4 vs T3 / T5 vs T4: comparison of improvement following iReadMore with real/sham tDCS

    T6 vs T5: maintenance of therapy benefits at follow-up assessment.



Secondary Outcome Measures:
  • Change in spoken word repetition for trained / untrained words [ Time Frame: Baseline and up to 3 months follow-up ] [ Designated as safety issue: No ]
    Accuracy of spoken word repetition for trained and untrained words will be assessed at T1-T6 and analysed using the same comparisons as word reading (primary outcome measure)

  • Change in semantic word matching for trained / untrained words [ Time Frame: Baseline and up to 3 months follow-up ] [ Designated as safety issue: No ]

    Reading for meaning (rather than reading aloud) will be assessed using a written word semantic matching task.

    Speed and accuracy of semantic matching for trained and untrained words will be assessed at T1-T6 and analysed using the same comparisons as word reading (primary outcome measure)



Other Outcome Measures:
  • Change in effective connectivity within the neural network involved in reading [ Time Frame: Baseline and up to 3 months follow-up ] [ Designated as safety issue: No ]

    Magnetoencephalography (MEG) will be used to investigate effective connectivity within the neural network involved in reading, using Dynamic Causal Modelling (DCM).

    Patients will be scanned immediately before the first block of therapy (T3) and again immediately after the first block of therapy (T4).

    A within-subjects comparison of effective connectivity at T3 vs T4 will identify changes resulting from the reading therapy.

    A between-subjects comparison of change in effective connectivity (T3 vs T4) between patients receiving real tDCS vs patients receiving sham tDCS during the first training block will identify changes resulting from the tDCS brain stimulation.


  • Change in grey matter or white matter volume [ Time Frame: Baseline and up to 3 months follow-up ] [ Designated as safety issue: No ]

    Structural magnetic resonance imaging (MRI) before and after therapy will be analysed using Voxel Based Morphometry (VBM) to identify changes in grey matter or white matter volume as a result of reading therapy.

    Patients will be scanned immediately before the first block of therapy (T3) and again immediately after the first block of therapy (T4).

    A within-subjects comparison of brain volume at T3 vs T4 will identify changes resulting from the reading therapy.

    A between-subjects comparison of change in brain volume (T3 vs T4) between patients receiving real tDCS vs patients receiving sham tDCS during the first training block will identify changes resulting from the tDCS brain stimulation.



Estimated Enrollment: 24
Study Start Date: March 2014
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Real tDCS

Transcranial direct current stimulation (tDCS) administered concurrently with computer-based behavioural word reading therapy.

2mA anodal direct current stimulation applied to the left inferior frontal gyrus (IFG) for first 20 minutes of therapy.

Behavioral: Computer-based behavioural word reading therapy

Each patient participates in two blocks of reading training (one with real tDCS, one with sham tDCS). Different words will be trained in each training block.

Each training block comprises 10 hours of reading therapy per week for four weeks (three 1-hour sessions/week at research site; 1-hour of training/day at home)

Other: Real tDCS
Real tDCS 20 minutes per session, three times per week
Sham Comparator: Sham tDCS

Transcranial direct current stimulation (tDCS) administered concurrently with computer-based behavioural word reading therapy.

Sham tDCS (periodical fade-in and fade-out stimulation routine) applied to the left inferior frontal gyrus (IFG) for first 20 minutes of therapy.

Behavioral: Computer-based behavioural word reading therapy

Each patient participates in two blocks of reading training (one with real tDCS, one with sham tDCS). Different words will be trained in each training block.

Each training block comprises 10 hours of reading therapy per week for four weeks (three 1-hour sessions/week at research site; 1-hour of training/day at home)

Other: Sham tDCS
Sham tDCS, 20 minutes per session, 3 sessions per week

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Over 18 years old
  • Left hemisphere stroke or other focal brain injury
  • English as a first language
  • At least one year post stroke
  • Impaired reading ability (defined according to screening with the Comprehensive Aphasia Test, CAT)
  • Mild to moderate aphasia (defined according to screening with the CAT)
  • Competent to give informed consent

Exclusion Criteria:

  • Hemorrhagic stroke
  • History of significant premorbid neurological or psychiatric illness
  • History of developmental reading or speech and language disability
  • Severe speech production deficit (defined according to screening with the CAT)
  • Damage to tDCS target region (left inferior frontal gyrus)
  • Contraindications to MRI scanning (e.g. presence of ferromagnetic implants or other metallic or electronic objects in the body; weight over 24 stone; claustrophobia or pregnancy).
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02062619

Contacts
Contact: Alex Leff, MBBS, PhD 0442076795429 a.leff@ucl.ac.uk
Contact: Zoe Woodhead, PhD 0442034484362 z.woodhead@ucl.ac.uk

Locations
United Kingdom
Institute of Neurology, University College London
London, United Kingdom, WC1N 3AR
Sponsors and Collaborators
University College, London
Investigators
Principal Investigator: Alex Leff, MBBS, PhD University College, London
  More Information

No publications provided

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT02062619     History of Changes
Other Study ID Numbers: MR/K022563/1
Study First Received: February 12, 2014
Last Updated: February 12, 2014
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University College, London:
Stroke
Aphasia
Acquired reading disorders
Central alexia
Computer based rehabilitation
Transcranial direct current stimulation
tDCS
Magnetoencephalography
MEG
Magnetic Resonance Imaging
MRI

Additional relevant MeSH terms:
Learning Disorders
Dyslexia
Aphasia
Stroke
Brain Injuries
Wounds and Injuries
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Mental Disorders Diagnosed in Childhood
Mental Disorders
Speech Disorders
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Craniocerebral Trauma
Trauma, Nervous System

ClinicalTrials.gov processed this record on July 22, 2014