NCT04968522

FASST - Fetal Alcohol Spectrum Stimulant Trial

Attention Management Trial for Children With FASD - a N-of-1 Control Trial of Prescribed Stimulants for ADHD in FASD

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Monash Medical Centre · Academic / Other
• Sex: All
• Age: 4 Years – 18 Years
• Healthy volunteers: Not accepted

Summary

This study is a double-blind, placebo controlled, series of N-of-1 trials of individualised stimulant dose on ADHD symptomatology in children with FASD. The broad aim of this study is to contribute new evidence towards understanding treatment efficacy for ADHD symptoms in FASD. Specific aims are: 1. To assess the ongoing effectiveness of stimulant medication prescribed for ADHD symptoms in individual children with FASD of clinically prescribed stimulant medication compared to placebo to control ADHD symptoms (using behavioural and cognitive measures) in children with FASD and ADHD using a N-of-1 trial design. 2. To obtain pilot data to examine feasibility and tolerability of the planned N-of-1 trial design in children with FASD and ADHD for future and larger studies that might seek to examine if the different stimulant types are equally effective relative to placebo. 3. To review the multiple N-of-1 data to analyze key individual factors that mediate the effect of stimulants relative to placebo on ADHD symptoms, including underlying child factors (attention skills, cognitive function), sociodemographic factors and other prenatal exposures.

Detailed description

Study Design: This is a single site, double-blind, placebo controlled, N-of-1 trial of clinically prescribed, individualised stimulant dose on ADHD symptomatology in children with FASD. The N-of-1 trial has four 2-week treatment blocks (each block consisting of 1 week active drug and 1 week placebo). Interventions will include either prescribed stimulant (active drug) or matched placebo capsules, compared in four 2-week treatment blocks (each block consisting of 1 week active drug and 1 week placebo). Participants will be randomized to the sequence of the treatment arms. Randomisation will be in the two-week pairs - so the order of treatment (A) and placebo (P) to be randomly assigned within each two-week cycle. Secondarily the investigators will collate outcomes across the N-of-1 trials and make use of a 'series' or multiple N-of-1 trial design18, chosen as it is a valid method of trial design for rare clinical disorders where individualized treatments are required. This design can result in robust evidence, assuming standards of methodological practice.1 In an N-of-1 trial, each participant is assured of receiving both the study medication and placebo, and thus learns whether the treatment works specifically for them or not. Study objectives: 1. Primary objective: Test ongoing effectiveness of stimulant medication in individual children with FASD on pharmacotherapy for ADHD symptomatology, using individual N-of-1 trials. 2. Secondary objectives: Secondary objective 1: To examine feasibility and tolerability of the N-of-1 trial design in children with FASD and ADHD for future, larger studies that might seek to examine if the different stimulant types are equally effective relative to placebo. Secondary objective 2: Through quantitative analysis of a series of N-of-1 trials,1 explore individual factors that mediate the effect of stimulants relative to placebo on ADHD symptoms, on children with FASD, including underlying attention skills, cognitive function and other child/sociodemographic factors and additional prenatal exposures. Exploratory objectives: Investigators will review if there is any change in pediatrician patient management post trial. Study Population: Children (4-18 years) with FASD and ADHD seen by the Victorian Fetal Alcohol Service (VicFAS), prescribed stimulant medication for ADHD symptoms. The age limit selected was based on the age in which stimulants have been shown to be effective in controlling ADHD symptoms in the general population, and who are seen by the clinical service. VicFAS assesses 20 children per year at the diagnostic clinic. All participants are currently approached for consent to the already established VicFAS database, which includes full child demographic, clinical and neurodevelopmental information as well as optional consent for future studies. Participants who have consented to this optional inclusion will be re-consented to this study. A total of 20 participants will be approached for recruitment to the study. This will be a convenience sample of children seen through the VicFAS FASD diagnostic clinic since inception in September 2019 until study completion (n=20). Each participant will undergo repeated measures. Estimation of the needed number of cross-overs (that is 'sample size' in N-of-1 studies) was based on having at least 80% power (β = 0.20) to detect a 5.9-point reduction. With 36 observations per participant, (18 placebo, 18 active medication) we achieve \>80% power (alpha of 0.05 will be used as the cut-off for significance, one-sided hypothesis test).

Conditions

• Fetal Alcohol Spectrum Disorders

Interventions

Type	Name	Description
DRUG	Methylphenidate Hydrochloride	This study is a N-of-1 RCT of currently prescribed stimulant medications for treatment of ADHD symptoms in children with FASD, relative to matched placebo capsules. The Ritalin 10 will be administered at the child's prescribed dose and may include a half tablet (5mg) increment. Ritalin 10 will be encapsulated in full tablet (10mg) or half tablet (5mg) dose.
DRUG	Placebo	The placebo is Maize Starch and Pregelatinised Maize Starch. The placebo will be encapsulated using the same capsule that is opaque so that participants cannot distinguish the two visually. Where the active mediation amount is small for the capsule, there will be additional Starcke 1500 (Maize Starch and Pregelatinised Maize Starch) added to fill the capsule so that the active drug and capsule also weigh approximately the same. The dose of placebo will be matched to the participants currently prescribed stimulant medication.
DRUG	Methylphenidate hydrochloride	This study is a N-of-1 RCT of currently prescribed stimulant medications for treatment of ADHD symptoms in children with FASD, relative to matched placebo capsules. The Ritalin LA will be administered at the child's prescribed total dose. Ritalin LA will be encapsulated.
DRUG	Methylphenidate Hydrochloride 18 MG	This study is a N-of-1 RCT of currently prescribed stimulant medications for treatment of ADHD symptoms in children with FASD, relative to matched placebo capsules. The Concerta (18mg) will be administered at the child's prescribed total dose. Concerta will be encapsulated.
DRUG	Dexamphetamine sulfate	This study is a N-of-1 RCT of currently prescribed stimulant medications for treatment of ADHD symptoms in children with FASD, relative to matched placebo capsules. The Dexamphetamine (10mg) will be administered at the child's prescribed total dose. Dexamphetamine will be encapsulated.

Timeline

• Start date: 2022-02-14
• Primary completion: 2023-04-01
• Completion: 2023-07-01
• First posted: 2021-07-20
• Last updated: 2022-12-13

Locations

1 site across 1 country: Australia

Regulatory

• FDA-regulated drug study