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Trial registered on ANZCTR


Registration number
ACTRN12623001147673
Ethics application status
Approved
Date submitted
11/10/2023
Date registered
6/11/2023
Date last updated
28/01/2024
Date data sharing statement initially provided
6/11/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD) and autism (MICAA) trial
Scientific title
Effectiveness of methylphenidate in children with co-occurring attention-deficit/hyperactivity disorder (ADHD) and autism - MICAA Trial
Secondary ID [1] 310579 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Attention-deficit/hyperactivity disorder 331434 0
Autism Spectrum Disorder 331435 0
Condition category
Condition code
Mental Health 328179 328179 0 0
Other mental health disorders
Mental Health 328180 328180 0 0
Autistic spectrum disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A series of double-blind, placebo controlled, n-of-1 trials of clinically prescribed, individualised methylphenidate immediate-release (MPH-IR) dose in children with ADHD+autism.
Interventions will include either prescribed MPH-IR (active drug) or matched placebo oral capsules, compared in six 2-week treatment blocks (each block consisting of 1 week active drug and 1 week placebo). Interventions will be administered daily from Monday-Friday during the 12-week trial. Weekends will act as washouts.
The dose of MPH-IR administered during active drug periods will follow the dosage schedule already prescribed by the participant's treating clinician (paediatrician or psychiatrist). It is likely for this individualised dose to be tolerated by the child, as they would have already been taking their prescribed dose prior to enrolment in the trial. Medication side-effects will be monitored weekly.
Treatment adherence will be monitored via participant medication diaries (doses taken/not taken). Tablets will be returned to study staff at the end of the trial.
Intervention code [1] 326986 0
Treatment: Drugs
Comparator / control treatment
Each child will act as their own control. Control treatment is a placebo (capsule containing inactive filler). Participants will take placebo medication for one week (Monday-Friday) during each of the six 2-week treatment blocks.
Control group
Placebo

Outcomes
Primary outcome [1] 336061 0
Participant ADHD traits, at an individual level, assessed using the teacher-rated Swanson, Nolan, and Pelham (SNAP-IV) questionnaire, a 26-item measure of inattention, hyperactivity/impulsivity and oppositional/defiant traits.
Timepoint [1] 336061 0
This outcome will be assessed weekly (each Friday) during the 12-week trial. Primary timepoint = comparison of MPH-IR week to placebo week ratings.
Primary outcome [2] 336063 0
Participant ADHD traits, at an individual level, assessed using the parent-rated Swanson, Nolan, and Pelham (SNAP-IV) questionnaire, a 26-item measure of inattention, hyperactivity/impulsivity and oppositional/defiant traits.
Timepoint [2] 336063 0
This outcome will be assessed weekly (each Friday) during the 12-week trial. Primary timepoint = comparison of MPH-IR week to placebo week ratings.
Secondary outcome [1] 426712 0
Participant ADHD traits, at a group level, assessed using the teacher-rated & parent-rated Swanson, Nolan, and Pelham (SNAP-IV) questionnaire, a 26-item measure of inattention, hyperactivity/impulsivity and oppositional/defiant traits.
Timepoint [1] 426712 0
This outcome will be assessed weekly (each Friday) during the 12-week trial.
Secondary outcome [2] 426713 0
Participant number and severity of adverse effects while "on" MPH-IR, assessed using the parent-rated Barkley Side Effect Rating Scale, a 17 item measure of possible stimulant medication side-effects.
Timepoint [2] 426713 0
This outcome will be assessed weekly (each Friday) during the 12-week trial.
Secondary outcome [3] 426714 0
Participant functional behaviour as assessed using the 'family' and 'school behaviour' items of the Weiss Functional Impairment Rating Scale Parent Version (WFIRS).
Timepoint [3] 426714 0
This outcome will be assessed weekly (each Friday) during the 12-week trial.
Secondary outcome [4] 426715 0
Participant autistic traits as assessed using the parent- and teacher-rated 'autism spectrum' items from the Weiss Symptom Rating Scale (WSR-II).
Timepoint [4] 426715 0
This outcome will be assessed weekly (each Friday) during the 12-week trial.
Secondary outcome [5] 426720 0
Participant emption regulation as assessed using the parent-rated SNAP-IV items plus four additional items from the 90-item SNAP, calculated as per Pylypow et al. (2020).
Timepoint [5] 426720 0
This outcome will be assessed weekly (each Friday) during the 12-week trial.
Secondary outcome [6] 426725 0
Participant self-reported anxiety, measured using the Visual Facial Anxiety Scale (VFAS).
Timepoint [6] 426725 0
This outcome will be assessed weekly (each Friday) during the 12-week trial.

Eligibility
Key inclusion criteria
Each participant (child) must meet all the following criteria to be enrolled in this trial:
- Is between the ages of 6 - 15 years at the time of enrolment.
- Has a clinical diagnosis of ADHD and of ASD.
- Has been taking a stable dose of MPH-IR (i.e. Ritalin 10) for one month prior to trial enrollment.
- Parent has signed and dated an informed consent form.
Minimum age
6 Years
Maximum age
15 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria will include any of the following:
- Inability to read or speak sufficient English for parent/guardian to complete assessment tasks.
- Is currently taking a medication other than MPH-IR (i.e. Ritalin 10) for the purpose of treating ADHD symptoms.
- Unable to swallow capsules.
- Has major illness or disability, including but not limited to: epilepsy, major head injury, Fragile X Syndrome or Williams Syndrome, Foetal Alcohol Spectrum Disorder (FASD) or Neonatal abstinence syndrome.
- Is known to be pregnant.
- Research team is not confident the child has both an ADHD and ASD diagnosis.
- Parent/guardian does not consent to contact with the clinician and school.
- Is deemed by their treating clinician (psychiatrist/paediatrician/GP) to be medically unfit for trial participation.
- Child’s school is unwilling to participate in outcome assessments.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will involve contacting the holder of the randomisation schedule.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer-generated randomisation schedule (random number sequence) created by the study statistician will be generated for each participant and held by the site pharmacies and not accessible to investigators.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
N-of-1 trial
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
29/01/2024
Actual
Date of last participant enrolment
Anticipated
6/10/2025
Actual
Date of last data collection
Anticipated
19/12/2025
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 314789 0
Government body
Name [1] 314789 0
Medical Research Future Fund, Million Minds: Growing Minds Australia
Country [1] 314789 0
Australia
Primary sponsor type
Individual
Name
Professor Katrina Williams
Address
Department of Paediatrics, Monash University | Monash Children’s Hospital, Level 5, 246 Clayton Road, Clayton VIC 3168
Country
Australia
Secondary sponsor category [1] 316776 0
Individual
Name [1] 316776 0
Professor Mark Bellgrove
Address [1] 316776 0
School of Psychological Sciences, Monash University, Room 540, 18 Innovation Walk, Clayton Campus, Clayton VIC 3800
Country [1] 316776 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313801 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 313801 0
Research Support Services, Monash Health, Level 2, I Block Monash Medical Centre, 246 Clayton Road, Clayton, Victoria, 3168
Ethics committee country [1] 313801 0
Australia
Date submitted for ethics approval [1] 313801 0
23/08/2023
Approval date [1] 313801 0
30/11/2023
Ethics approval number [1] 313801 0

Summary
Brief summary
The Methylphenidate in Children with ADHD+Autism (MICAA) Trial will use N-of-1 trial methodology to individually test the effectiveness of MPH-IR in ~40 children (aged 6-15 years) with ADHD+autism. Participants will include children who have been taking a stable dose of MPH-IR for at least one month prior to trial enrollment. The children will cycle through 12 randomised weekly periods of “on” (MPH-IR) or “off” (placebo) medication, with allocation concealment. There will be weekly monitoring of primary outcomes (ADHD symptoms), and secondary outcomes, including autistic traits, functional behaviour, emotion regulation, anxiety and medication side effects. Study findings will identify those children who are not responding to their prescribed medication, prompting a review of treatment decisions.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 129386 0
Prof Katrina Williams
Address 129386 0
Monash Children’s Hospital, Level 5, 246 Clayton Road, Clayton VIC 3168
Country 129386 0
Australia
Phone 129386 0
+61 3 857 23947
Fax 129386 0
Email 129386 0
[email protected]
Contact person for public queries
Name 129387 0
Mark Bellgrove
Address 129387 0
Monash University, Room 540, 18 Innovation Walk, Clayton Campus, Clayton VIC 3800
Country 129387 0
Australia
Phone 129387 0
+61 3 9902 4200
Fax 129387 0
Email 129387 0
[email protected]
Contact person for scientific queries
Name 129388 0
Mark Bellgrove
Address 129388 0
Monash University, Room 540, 18 Innovation Walk, Clayton Campus, Clayton VIC 3800
Country 129388 0
Australia
Phone 129388 0
+61 3 9902 4200
Fax 129388 0
Email 129388 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
After de-identificaiton, individual participant data underlying published results.
When will data be available (start and end dates)?
Immediately following publication.
Available to whom?
Data and analysis scripts will be made publicly available via open-access repositories.
Available for what types of analyses?
Unrestricted, but most typically for inclusion in meta-analysis or reanalysis of data pursuing different aims.
How or where can data be obtained?
Monash University Research Repository.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.