Methylphenidate in Childhood Apraxia of Speech

Single word speech intelligibility will be measured using the Preschool Speech Intelligibility Measure (PSIM). Twenty (20) items from the PSIM will be administered at each testing time point. Participants are required to repeat each test word after the researcher. Higher scores are indicative of greater unintelligibility (range 0-80). Mean change from baseline will be reported at the group level.

The Assessment of the Intelligibility of Dysarthric Speech-II (ASSIDS-II) will be used to measure sentence level speech intelligibility. Five (5) 5-word sentences will be administered at each assessment time point. A phonemic accuracy score will be calculated by determining the percentage of correct phonemes across the 5 sentences at each timepoint. Mean change from baseline will be reported at the group level.

The frequency of children at screening who refuse, are eligible, or are ineligible (and reason).

Number of children in either sequence A or B who:

• withdraw
• discontinue the treatment prior to 4 weeks
• experience 1 or more protocol violations.

Adherence will be determined by calculating the percentage of prescribed doses achieved based on the medication diary entries and reconciling against returned dispensed medication. A participant will be considered adherent during a 4-week period if 80% of the prescribed doses are achieved. Data will be aggregated such that the proportion of children who adhere to the dosing regimen in each 4-week period will be reported.

Measured using the investigators' parent/caregiver tolerability and utility survey which is a dedicated electronic Case Report Form. This provides data on caregiver(s)'s views of usability (e.g., "It was convenient to give my child the capsules"), tolerability (e.g., "It was not a burden to participate in this trial") and experience of the trial (Vogel, 2016) (e.g., "I am glad my child participated in this trial"), and whether speech was improved (e.g., "I think the capsule improved my child's speech"). Items will be rated 1-5 where a score of 1 indicates the parent/caregiver strongly disagrees and a score of 5 indicates the parent/caregiver strongly agrees. One item related to school can be rated as 0 if the child is on holidays or in a COVID-19 lockdown for the trial duration. Total scores range from 20-105, where a higher score indicates a greater tolerability/utility of the trial as rated by the parent. Mean change from baseline will be reported at the group level.

Measured using the investigators' patient tolerability and utility survey which is a dedicated electronic Case Report Form (eCRF). This provides data on participants' views of usability (e.g., "It was easy to take the capsules"), tolerability/burden (e.g., "I had enough energy to play when taking the capsules") and experience of the trial (Vogel, 2016) (e.g., "I would do this trial again"), and whether speech was improved (e.g.,"I think my speech is better after taking the capsules"). Items will be rated 1-5 where a score of 1 indicates the participant strongly disagrees with the statement and a score of 5 indicates the participant strongly agrees. One item related to school can be rated as 0 if the child is on holidays or in a COVID-19 lockdown for the duration of the trial. Total scores range from 20-105, where, a higher score indicates a greater tolerability/utility of the trial as rated by the child participant. Mean change from baseline will be reported at the group level.

Children's conversational speech will be analysed to determine the total number of grammatical features present using the Language Assessment, Remediation and Screening Procedure (LARSP). Mean change from baseline will be reported at the group level.

Children's conversational speech will be analysed to determine the total number of sentences present using the Language Assessment, Remediation and Screening Procedure (LARSP). Mean change from baseline will be reported at the group level.

Children's conversational speech will be analysed to determine the total number of sentences per turn using the Language Assessment, Remediation and Screening Procedure (LARSP). Mean change from baseline will be reported at the group level.

Children's conversational speech will be analysed to determine the mean sentence length produced using the Language Assessment, Remediation and Screening Procedure (LARSP). Mean change from baseline will be reported at the group level.

Children's conversational speech will be analysed to determine the child's stage of grammatical development, identified using the Language Assessment, Remediation and Screening Procedure (LARSP). Mean change from baseline will be reported at the group level.

Children's conversational speech will be analysed to determine types of clausal structures used by the child, identified using the Language Assessment, Remediation and Screening Procedure (LARSP). Aggregated data will be reported.

Syllable repetition will be measured by analysing the average number of syllables produced, average period or duration between consonant-vowel syllable voicing offsets (milliseconds) and variance of the diadochokinetic period (percentage reported). Mean change from baseline will be reported at the group level, and will be compared between Sequence A and Sequence B.

The Intelligibility in Context Scale (ICS) will measure functional speech intelligibility using parent/caregiver ratings across 7 items, where high scores are indicative of poor intelligibility of speech (range 7-35). Mean change from baseline will be reported at the group level.

The Children's Non-word Repetition (CNRep) Test will measure phonological working memory. Ten CNRep items will be administered at each of the four assessment timepoints to control for learning effects. The percentage of correct responses will be calculated by syllable (i.e., 2, 3, 4 and 5 syllable words) and for the total list of words. Mean change from baseline will be reported at the group level.

The Swanson, Nolan, and Pelham (SNAP-IV) Questionnaire is a measure of Attention Deficit Hyperactivity Disorder (ADHD) symptoms using ADHD diagnostic criteria specified in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Parent ratings on the Attention and Hyperactivity subscales will be used to measure attention deficit and hyperactivity symptoms. Higher scores indicate greater inattentive and/or hyperactive behaviours. Scores on each subscale range from 0-27. A score below 13 is indicative of symptoms not being clinically significant. A score of 13-17 indicates mild symptoms; a score of 18-22 indicates moderate symptoms and a score of 22-27 indicates severe symptoms. Mean change from baseline will be reported at the group level.

Maximum phonation time will be measured by determining the maximum length of a continuous vowel phonation on one breath to indicate airflow sufficiency and adequacy of vocal folds closure. Mean change from baseline will be reported at the group level, and will be compared between Sequence A and Sequence B.

Vowel space measurements can provide objective information on formant distribution and act as a proxy for vowel production. Vowel space will be quantified by using the vowel articulation index (see Sapir et al. (2009) for more information). Mean change from baseline will be reported at the group level, and compared between Sequence A and Sequence B.

Mel-frequency cepstral coefficient (MFCC) measures subtle changes in the motion of the articulators (jaw, tongue, lips). The MFCC coefficient represents the vocal tract transfer function, indicating potential problems in the articulators. The MFCC was designed to represent overall stability of individual vocal tract elements. The MFCC parameter is defined as the mean of the standard deviations of the 1st-12th MFCCs. See Fraile et al. (2009) for further description. Mean change from baseline will be reported at the group level, and compared between Sequence A and Sequence B.

The mean of pause length of speech measures the average length of silence in a speech sample. The mean of pause length will be analysed by determining the number of silences divided by the total silence duration (msec). Mean change from baseline will be reported at the group level, and will be compared between Sequence A and Sequence B.

The standard deviation of pauses of speech measures the variability in pause length. Mean change from baseline will be reported at the group level, and will be compared between Sequence A and Sequence B.

The percentage of silence of speech measures the proportion of silence derived from total pause duration divided by total signal time. Mean change from baseline will be reported at the group level, and will be compared between Sequence A and Sequence B.

The rate of speech is derived from number of syllables spoken per second. The rate of speech will be analysed by determining the number of syllables spoken in a duration of a speech sample. Mean change from baseline will be reported at the group level, and will be compared between Sequence A and Sequence B.

The Pairwise Variability Index (PVI) is a measure of relative vowel duration across adjacent syllables in a word or sentence that is normalised to allow comparison across different speech rates (Vergis et al., 2014). PVI is calculated by determining the difference in duration for two adjacent syllables and then dividing the difference by an average of the two values. Higher PVI values indicate greater contrastiveness, while values close to zero indicate equal stress. Mean change from baseline will be reported at the group level, and will be compared between Sequence A and Sequence B.