Clinical trial NCT05185583: Methylphenidate in Childhood Apraxia of Speech
Official title: A Phase II Proof-of-concept Trial of Methylphenidate in Children With Apraxia of Speech: a Double-blind, Randomised, Placebo-controlled, Cross-over Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Childhood Apraxia of Speech
Keywords: Childhood Apraxia of Speech
Methylphenidate
Ritalin
Developmental Verbal Apraxia
Apraxia, Verbal
Attention Deficit-Hyperactivity Disorder
Central Stimulants
Central Nervous System (CNS) Stimulants
Intelligibility, Speech
Lead sponsor: Murdoch Childrens Research Institute
Sponsor class: OTHER
First posted: 2022-01-11
Enrollment: 24
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to describe the possible effects of methylphenidate (MPH) on speech intelligibility in children with childhood apraxia of speech (CAS) aged 6-12 years. This outcome will be compared between MPH intake and placebo intake.

Detailed description: This is a randomised, double-blind, placebo-controlled, two-period crossover proof-of-concept trial of methylphenidate (MPH) for children with childhood apraxia of speech (CAS). 24 children aged 6 to 12 years with CAS will be recruited. If children pass the screening procedure, which includes a physical exam conducted by a medical officer at the Melbourne Children's Campus, children will be enrolled into the 8 weeks + 2-day trial (includes 2-day washout). Participants will be randomly assigned to sequence A (4 weeks of MPH, followed by 4 weeks of placebo) or sequence B (4 weeks of placebo, followed by 4 weeks of MPH). After 4 weeks in period 1, a two-day washout period will occur before participants crossover to period 2 for 4 weeks. Pre- and post-treatment speech outcomes will be measured. The investigators' primary objective is to provide proof-of-concept that speech intelligibility could demonstrate greater improvements from baseline to 4 weeks following a 4-week period of MPH use compared with placebo in children with CAS. The secondary objectives are to describe feasibility, tolerability and change from baseline in: connected speech intelligibility, quality of language production, speech quality, functional speech intelligibility, phonological working memory, attentional and hyperactive behaviour.

Eligibility criteria: Inclusion Criteria:

* Has childhood apraxia of speech
* Aged 6-12 years
* Can perform the speech tasks for the trial (able to speak single words and short sentences)
* English as a first language
* Has adequate hearing
* Has a legally acceptable representative capable of understanding the informed consent document and providing consent on their behalf
* Passes the health and medical examination including examination of heart rate and blood pressure for age and weight norms
* Can commit to the time requirements of the trial
* Lives within 250 kilometres of the study site (MCRI)
* Able to swallow a capsule
* Scores 13 or more out of 27 on either the inattention and/or hyperactivity subscales of the SNAP-IV Parent 18-Item Rating Scale, suggesting clinically significant symptoms of inattention and/or hyperactivity

Exclusion Criteria:

* Is unable to commit to the time requirements of the trial (8 weeks + 2 days)
* Has a diagnosis of severe intellectual disability, or other significant neurodevelopmental conditions (e.g., Fragile X, Down Syndrome, etc.)
* Has epilepsy or other seizure disorders
* Is taking medication(s) for another health condition(s) that is known to interfere with MPH
* Has any contraindication to the stimulant (methylphenidate) medication, including severe anxiety, depression, severe Tourette syndrome, glaucoma, psychotic symptoms, hypertension, congenital heart disease, known past or present diagnosed substance abuse or dependence
* Has a score of moderate or high risk of suicidality, assessed with the Columbia Suicidality Severity Rating Scale (C-SSRS)
* Has used psychostimulants within the past 3 months (e.g., Ritalin, Concerta, Focalin)
* Lives more than 250 kilometres from the study site
* Unable to swallow a capsule

Primary outcomes:
measure: Change From Baseline in Preschool Speech Intelligibility Measure Score at 4 weeks
timeFrame: Baseline and 4 weeks
Secondary outcomes:
measure: Change From Baseline in Assessment of the Intelligibility of Dysarthric Speech-II (ASSIDS-II) Score at 4 weeks
timeFrame: Baseline and 4 weeks
measure: Number of children at screening who refuse, are eligible, or are ineligible (and reason).
timeFrame: At study recruitment, up to 4 weeks before starting treatment.
measure: Number of children who withdraw, discontinue, and/or experience 1 or more protocol violations.
timeFrame: During the 4 week treatment phase.
measure: Adherence to dose regimen during each 4 week treatment period
timeFrame: 4 weeks
measure: Parent/caregiver experience of tolerability and utility
timeFrame: Baseline and 4 weeks
measure: Paediatric patient experience of tolerability and utility
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in total number of grammatical features (Language Assessment, Remediation and Screening Procedure; LARSP) at 4 weeks
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in total number of sentences (Language Assessment, Remediation and Screening Procedure; LARSP) at 4 weeks
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in mean number of sentences per turn (Language Assessment, Remediation and Screening Procedure; LARSP) at 4 weeks
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in mean sentence length (Language Assessment, Remediation and Screening Procedure; LARSP) at 4 weeks
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in stage of grammatical development (Language Assessment, Remediation and Screening Procedure; LARSP) at 4 weeks
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in types of clausal structures used (Language Assessment, Remediation and Screening Procedure; LARSP) at 4 weeks
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in syllable repetition at 4 weeks
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in Intelligibility in Context Scale Score at 4 weeks
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in Children's Non-word Repetition (CNRep) Test Score at 4 weeks
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in Swanson, Nolan, and Pelham (SNAP-IV) Parent 18-Item Rating Scale (SNAP-IV) Score at 4 weeks
timeFrame: Baseline and 4 weeks
Other outcomes:
measure: Change From Baseline in maximum phonation time at 4 weeks
timeFrame: Baseline and 4 weeks
measure: Change from Baseline in vowel space of speech at 4 weeks
timeFrame: Baseline and 4 weeks
measure: Change from Baseline in the Mel-frequency cepstral coefficient (MFCC) at 4 weeks
timeFrame: Baseline and 4 weeks
measure: Change from Baseline in mean of pause length of speech at 4 weeks
timeFrame: Baseline and 4 weeks
measure: Change from Baseline in standard deviation of pauses of speech at 4 weeks
timeFrame: Baseline and 4 weeks
measure: Change from Baseline in percentage of silence at 4 weeks
timeFrame: Baseline and 4 weeks
measure: Change from Baseline in rate of speech at 4 weeks
timeFrame: Baseline and 4 weeks
measure: Change from Baseline in pairwise variability index at 4 weeks
timeFrame: Baseline and 4 weeks
Locations:
city: Parkville
country: Australia
facility: Murdoch Children's Research Institute
state: Victoria
Study officials:
affiliation: Murdoch Childrens Research Institute
name: Angela Morgan, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fraile R, Saenz-Lechon N, Godino-Llorente JI, Osma-Ruiz V, Fredouille C. Automatic detection of laryngeal pathologies in records of sustained vowels by means of mel-frequency cepstral coefficient parameters and differentiation of patients by sex. Folia Phoniatr Logop. 2009;61(3):146-52. doi: 10.1159/000219950. Epub 2009 Jul 1.
citation: Sapir S, Ramig LO, Spielman JL, Fox C. Formant centralization ratio: a proposal for a new acoustic measure of dysarthric speech. J Speech Lang Hear Res. 2010 Feb;53(1):114-25. doi: 10.1044/1092-4388(2009/08-0184). Epub 2009 Nov 30.
citation: Vergis, Ballard, K. J., Duffy, J. R., McNeil, M. R., Scholl, D., & Layfield, C. (2014). An acoustic measure of lexical stress differentiates aphasia and aphasia plus apraxia of speech after stroke. Aphasiology, 28(5), 554-575. https://doi.org/10.1080/02687038.2014.889275
citation: Vogel, A., Skarrat, J., Castles, J., Synofzik, M. . (2016). Video game-based speech rehabilitation for reducing dysarthria severity in adults with degenerative ataxia. European Journal of Neurology, 23(227).