Multimodal intervention in 8- to 13-year-old French dyslexic readers: Study protocol for a randomized multicenter controlled crossover trial

Background Developmental dyslexia, a specific and long-lasting learning disorder that prevents children from becoming efficient and fluent readers, has a severe impact on academic learning and behavior and may compromise professional and social development. Most remediation studies are based on the explicit or implicit assumption that dyslexia results from a single cause related to either impaired phonological or visual-attentional processing or impaired cross-modal integration. Yet, recent studies show that dyslexia is multifactorial and that many dyslexics have underlying deficits in several domains. The originality of the current study is to test a remediation approach that trains skills in all three domains using different training methods that are tailored to an individual’s cognitive profile as part of a longitudinal intervention study. Methods This multicenter randomized crossover study will be conducted in three phases and will involve 120 dyslexic children between the ages of 8 and 13 years. The first phase serves as within-subject baseline period that lasts for 2 months. In this phase, all children undergo weekly speech-language therapy sessions without additional training at home (business-as-usual). During the second phase, all dyslexics receive three types of intensive interventions that last 2 month each: Phonological, visual-attentional, and cross-modal. The order of the first two interventions (phonological and visual-attentional) is swapped in two randomly assigned groups of 60 dyslexics each. This allows one to test the efficacy and additivity of each intervention (against baseline) and find out whether the order of delivery matters. During the third phase, the follow-up period, the intensive interventions are stopped, and all dyslexics will be tested after 2 months. Implementation fidelity will be assessed from the user data of the computerized intervention program and an “intention-to-treat” analysis will be performed on the children who quit the trial before the end. Discussion The main objective of this study is to assess whether the three types of intensive intervention (phase 2) improve reading skills compared to baseline (i.e., non-intensive intervention, phase 1). The secondary objectives are to evaluate the effectiveness of each intervention and to test the effects of order of delivery on reading intervention outcomes. Reading comprehension, spelling performance and reading disorder impact of dyslexic readers are assessed immediately before and after the multimodal intervention and 2 months post-intervention. Trial registration ClinicalTrials.gov, NCT04028310. Registered on July 18, 2019. Supplementary Information The online version contains supplementary material available at 10.1186/s12887-022-03701-8.

§ The end-of-study date: It is the date of the last information collected as part of the study. No review related to the study, administration of the treatment under study, or data collection will be carried out after that date. The end-of-study date may be the date of the last visit or the date of the last information collected as part of the visit. § Early exit: If the patient leaves the study before the end of the study, please specify the reason for this premature exit. If in doubt do not hesitate to contact the sponsor CRA (Clinical Research Associate) or the coordinating investigator. Premature exit by the patient: the patient may decide at any time to interrupt his or her participation in the study (refusal to continue / withdrawal of consent). All the data collected until the exit will be collected and analyzed (Jardé Law -Article L.1121-1-1du CSP, 18 th November 2016 version).

5-CONTACT:
If any problems arise when filling out the CRF, please contact the sponsor (contact details mentioned on page 1).

6-Specific conventions for filling out the CRF: §
The data is collected in the tables included in this CRF in raw scores, Z scores and percentiles according to the instructions provided in the manuals for each test. § For children with "high intellectual potential" the reading age must be compared with the age of development and not with the actual age. § For Alouette©, two calibrations are used: the first calibration for the reading age and the second calibration dating from 2005. § For DeltaText and Likert scales, there are no Z scores. § Training is adapted to the cognitive profile of each child. For example, the child that does not have a visuo-attentional span disorder will complete 2 months of training with Switchipido© and will not practice with Maeva©. Therefore, the pre-and post-training baseline tables for Maeva© will not be used. Note in the patient's source file the patient's participation in the study and the patient's consent.
In the absence of one of the parents, a prior oral agreement of the absent parent must be obtained and notified in the patient's medical file.
Contact information and written consent of the absent parent should be collected as soon as possible.
If one of the parents has not signed the consent form, the investigator must provide evidence in the child's source file of having tried to contact the parent.

SELECTION TESTS, READING AND SPELLING
For the administration of the tests, refer to the instruction manual -Reading meaningless text (Alouette©) -Spelling (Chronosdictées©, version A)

SELECTION CRITERIA Yes No
Age ≥ 8 and £ 13 q q Diagnosis of dyslexia or difficulty in reading and/or spelling q q Absence of perceptual, neurological or behavioral disorders q q No oral language problems q q Native language: French or early school in French q q No attentional problems q q No rehabilitation is underway q q Home equipped with a computer connected to internet for daily training q q Informed consent signed by both parents or the representative of the parental authority q q Social Security affiliation or beneficiary q q

INCLUSION VISIT -PHASE 1-TEST 1-V 2 to V 4
To administer and determine the order of tests, refer to the manual sent to you that specifies the order to be followed.

INCLUSION CRITERIA Yes No
Age greater than or equal to 8 years and less than or equal to 13 years. q q Diagnosis of dyslexia validated by performance lower than 1.5 standard deviation from the average developmental age on the Alouette© test and the reading tasks of irregular words and non-words (Evalec©) q q Performance lower or equal to -1.5 standard deviation from the average in at least one phonological task (Evalec©) and at least one visuo-attentional task (Sigl©, Evadys©) q q Home equipped with a computer connected to internet for daily training q q Informed consent signed by one of the parents or the representative of the parental authority q q Social Security affiliate or beneficiary q q

NON-INCLUSION CRITERIA Yes No
Intellectual delay or neurological disorders or global developmental disorder q q Primary sensory deficit q q Educational deficiencies q q Attention Deficit Disorder with or without Hyperactivity (ADHD) q q Specific oral language impairment q q Previous daily phonological or visuo-attentional training q q

RANDOMIZATION
At the end of the inclusion visits, send your randomization sheet to: karine.eskinazi@wanadoo.fr The coordinating investigator will tell you whether participants are assigned to group 1 or group 2 and will send you the appropriate CRFs following the study.
-Group 1: PHONO 1 -VA 2-IM 3 -Group 2: VA 1-PHONO 2-IM 3 The participant is not informed of his or her attribution to group 1 or 2 and will follow the instructions given by the associate investigative speech therapist regarding the conduct of the study.