Brain Mechanisms Underlying Reading Improvement in Central Alexia

NCT02062619 | Completed DMC

• 1 other identifier: MR/K022563/1
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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. 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. 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.

Conditions

Stroke; Brain Injuries; Aphasia

Keywords

Stroke; Aphasia; Acquired reading disorders; Central alexia; Computer based rehabilitation; Transcranial direct current stimulation; tDCS; Magnetoencephalography; MEG; Magnetic Resonance Imaging; MRI

Outcome Measures

Primary Outcomes (1)

• Change in word reading speed and accuracy for trained and untrained words

  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.

  Baseline and up to 3 months follow-up

Secondary Outcomes (2)

• Change in spoken word repetition for trained / untrained words

  Baseline and up to 3 months follow-up

• Change in semantic word matching for trained / untrained words

  Baseline and up to 3 months follow-up

Other Outcomes (2)

• Change in effective connectivity within the neural network involved in reading

  Baseline and up to 3 months follow-up

• Change in grey matter or white matter volume

  Baseline and up to 3 months follow-up

Study Arms (2)

Real tDCS

EXPERIMENTAL

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; Other: Real tDCS

Sham tDCS

SHAM COMPARATOR

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; Other: Sham tDCS

Interventions

Computer-based behavioural word reading therapy BEHAVIORAL

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)

Real tDCS; Sham tDCS

Real tDCS OTHER

Real tDCS 20 minutes per session, three times per week

Real tDCS

Sham tDCS OTHER

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

Sham tDCS

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• University College, London: lead

Study Sites (1)

Institute of Neurology, University College London

London, WC1N 3AR, United Kingdom

Location

Related Publications (2)

• Kerry SJ, Aguilar OM, Penny W, Crinion JT, Leff AP, Woodhead ZVJ. How Does iReadMore Therapy Change the Reading Network of Patients with Central Alexia? J Neurosci. 2019 Jul 17;39(29):5719-5727. doi: 10.1523/JNEUROSCI.1426-18.2019. Epub 2019 May 13.

  PMID: 31085605 DERIVED

• Woodhead ZVJ, Kerry SJ, Aguilar OM, Ong YH, Hogan JS, Pappa K, Leff AP, Crinion JT. Randomized trial of iReadMore word reading training and brain stimulation in central alexia. Brain. 2018 Jul 1;141(7):2127-2141. doi: 10.1093/brain/awy138.

  PMID: 29912350 DERIVED

MeSH Terms

Conditions

Stroke; Brain Injuries; Aphasia

Condition Hierarchy (Ancestors)

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

Study Officials

• Alex Leff, MBBS, PhD

  University College, London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2014
• First Posted: February 13, 2014
• Study Start: March 1, 2014
• Primary Completion: July 1, 2016
• Study Completion: September 1, 2016
• Last Updated: November 4, 2016

Record last verified: 2016-04

Locations

GB (1)