Fetal Alcohol Spectrum DisordersPhase 4FASSTNCT04968522
FASST - Fetal Alcohol Spectrum Stimulant Trial
A Phase 4 study testing Methylphenidate Hydrochloride, Methylphenidate Hydrochloride 18 MG and Dexamphetamine sulfate in people with Fetal Alcohol Spectrum Disorders, run by Monash Medical Centre at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 to 18 years
- Conditions the study is for
- Fetal Alcohol Spectrum Disorders
- What is being tested?
- Methylphenidate Hydrochloride, Methylphenidate Hydrochloride 18 MG and Dexamphetamine sulfate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteAustralia
- Study dates
- 14 Feb 2022to Jul 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Each patient must meet all of the following criteria to be enrolled in this trial:
- Is between the ages of 4 - 18 years at the time of randomization.
- Meet diagnostic criteria for FASD or at risk of FASD according to the Australian Guide to the diagnosis of FASD.
- Is a patient of VicFAS or Developmental Paediatrics (Monash Health).
- Has a diagnosis of ADHD according to the DMS-IV criteria.
- Be on a stimulant medication for treatment of ADHD symptoms.
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- Be on a stimulant medication as a primary treatment for ADHD.
- Be on a stable dose of stimulant medication for at last 1 month prior to the study.
- Provide a signed and dated informed consent form / and has a legally acceptable representative capable of understanding the informed consent document and providing consent on the participant's behalf.
- If seen by VicFAS/Developmental paediatrics between August 2019 - study commencement date), parent/guardian must have provided verbal or written consent to the VicFAS database PICF and selected 'yes' to the optional consent for contact for 'future research'.
Who cannot join
- Inability to read or speak sufficient English for either child or parent/guardian to complete assessment tasks.
- Be on a medication for treatment of ADHD symptoms that is a medication other than stimulants as a primary treatment for ADHD.
- Allergy/sensitivity to Starcke 1500 (Maize Starch and Pregelatinised Maize Starch).
- Unable to swallow capsules.
- Intracranial symptoms or pathology such as epilepsy, hydrocephalus, diagnosed traumatic. brain injury or progressive intracranial tumours that may impact cognitive and behavioural function (children with asymptomatic or static lesions will be eligible).
- An abnormal ECG result at the time of screening deemed clinically significant by study physician.
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- Presence of a significant comorbid psychiatric or psychological (excluding ADHD, oppositional defiant disorder, conduct disorder and pervasive development disorder/autism spectrum disorder) including depressive disorder, anxiety disorder, psychotic disorder, suicidality, Tic disorder, anorexia or bulimia nervosa
- Has a known hypersensitivity to starch or other compound relevant to placebo/capsules.
- Has had treatment with any other investigational drug within 4 weeks prior to randomisation.
- If the participant is known to be pregnant, they cannot take part in this research project.
- Parent/guardian not consenting to contact with paediatrician or school.
- Is deemed by their treating paediatrician to be medically unsafe for trial participation.
- Child's school unwilling to participate in outcome assessments.
Trial locations and contacts
1 site in 1 country.
Australia1 site, 1 recruiting
- Recruiting
Monash Health
Clayton, Victoria, 3168
Alison Crichton, 0428214717, ali.crichton@monashhealth.org
About this study
Official title: Attention Management Trial for Children With FASD - a N-of-1 Control Trial of Prescribed Stimulants for ADHD in FASD
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.
Read more
Specific aims are:
- 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.
- 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.
- 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.
Read the 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:
- Primary objective: Test ongoing effectiveness of stimulant medication in individual children with FASD on pharmacotherapy for ADHD symptomatology, using individual N-of-1 trials.
- 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
- Being tested
- Methylphenidate Hydrochloride, Placebo, Methylphenidate Hydrochloride 18 MG, Dexamphetamine sulfate
- Keywords
- Attention Deficit Hyperactivity Disorder, Stimulants, Trial, Attention
- Medical subject headings
- Fetal Alcohol Spectrum Disorders, Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylphenidate HydrochlorideDrug
Also called Ritalin 10 tablets
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.
PlaceboDrug
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.
Methylphenidate hydrochlorideDrug
Also called Ritalin LA Long acting capsules
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.
Methylphenidate Hydrochloride 18 MGDrug
Also called Concerta
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.
Dexamphetamine sulfateDrug
Also called Aspen Dexamfetamine Tablets
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.
| Study group | Role | What they receive |
|---|---|---|
| Placebo comparator 2 | Placebo comparator | Participants will be allocated a randomly allocated sequence of treatment. The randomisation will be in two-week pairs - so the order of treatment (A) and placebo (P) to be randomly assigned within each two-week cycle (over 8 weeks). Placebo will be matched in dose to their stimulant dose at enrolment to the trial as determined and titrated by their primary paediatrician. This dose will remain constant for the course of the trial (8 weeks). Placebo will be orally administered, unless this is not possible for clinical reasons. Receives: Drug: Placebo |
| Stimulant | Experimental | The stimulants used in the trial are commercially available and will be used in accordance with the approved labelling. Participants must be on a stable dose of stimulant medication for at last 1 month prior to the study. The dose is individualized and titrated by treating primary paediatrician. This will represent the starting dose for the trial, and this will remain stable through the course of the 8-week trial. 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. Based on pilot data from this group, psychostimulant medications prescribed in this population may include:
* Methylphenidate IR
* Methylphenidate LA
* Dexamphetamine
Children will take the required number of capsules to match the total prescribed dose (e.g. 30mg Ritalin LA is 3x10mg capsules). Receives: Drug: Methylphenidate Hydrochloride; Drug: Methylphenidate Hydrochloride 18 MG; Drug: Dexamphetamine sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in ADHD symptoms - teacher report - between placebo and stimulant
ADHD symptoms will be measured using the Conners 3rd Edition-Teacher (Conners 3-T), for 6-18 year old's and the Conners Early Childhood teachers/childcare providers (full length) form for participants 2-6 years. Each item is rated on a Likert scale from 0 to 3 (0=never or rarely; 1=sometimes; 2=often; 3=very often). Test- retest values for the Conners scales indicate excellent temporal stability (ranging from .73 to 1.00).
The T-score is norm referenced, with a mean of 50. The average range falls within one standard deviation of the mean (i.e., between 40 and 59). A higher score indicates more elevated symptoms. T score Guideline 70+Very Elevated Score 65-69 Elevated Score 40-59 Average score 60-64 High average score < 40 Low score. Investigators will examine Inattentive and Hyperactivity/Impulsivity Symptom Scales. Symptoms indicated for each subscale are summed to get total.
Measured: Daily for 5 week days (Monday - Friday) of each trial week (8 weeks total)
Change in ADHD symptoms - parent report - between placebo and stimulant
ADHD symptoms will be measured using the Conners 3rd Edition-Parent (Conners 3-P), for 6-18 year old's and the Conners Early Childhood parent (full length) form for participants 2-6 years. Each item is rated on a Likert scale from 0 to 3 (0=never or rarely; 1=sometimes; 2=often; 3=very often). Test- retest values for the Conners scales indicate excellent temporal stability (ranging from .73 to 1.00).
The T-score is norm referenced. The average range falls within one standard deviation of the mean (i.e., between 40 and 59). A higher score indicates more elevated symptoms. T score Guideline 70+Very Elevated Score 65-69 Elevated Score 40-59 Average score 60-64 High average score < 40 Low score. Investigators will examine Inattentive and Hyperactivity/Impulsivity Symptom Scales. Symptoms indicated for each subscale are summed to get the total.
Measured: Daily for 5 week days (Monday - Friday) of each trial week (8 weeks total)
Change in spatial working memory - between placebo and stimulant
Spatial Working Memory (SWM) task from the Cambridge Neuropsychological Test Automated Battery. SWM is a component of cognitive executive function which is measured by SWM task of CANTAB between the errors. The ability to retain spatial information and manipulate remembered items in working memory will be measured with the SWM task of CANTAB which is self-ordered and assesses the individual's ability to strategise. Between search errors will be analysed. Scores are raw scores, with no normative data available. Higher error score indicated poorer performance. Scale does not have a maximum range.
Measured: Day 3 of each trial week (8 weeks total)
Change in Visual Information Processing - between placebo and stimulant
Rapid Visual Information Processing (SOC) from Cantab. SOC Stockings of Cambridge (SOC) is a test of spatial planning that requires individuals to use problem-solving strategies to match two sets of stimuli. The participant must move the balls in the bottom display to copy the pattern shown in the top display. The balls are moved one at a time by selecting the required ball, then selecting the position to which it should be moved. The participant is instructed to make as few moves as possible to match the two pattern.
The outcome measure of this subtest is the number of problems completed, regardless of whether the maximum moves limit was reached on any problem.
Measured: Day 3 of each trial week (8 weeks total)
Secondary outcomes (9)
Change in child problem behaviour rating- between placebo and stimulant
Top Problem Rating. This will be used as a brief but robust measure of child emotional and behavioural difficulties as rated by the parent. Top Problems Assessment (TPA) is a brief, idiographic procedure that allows clinicians and researchers to identify problems of children that are especially important from the perspective of the caregiver. The severity of these problems, once identified, will monitored daily.
The overall severity of problem rating (0 - 4) between placebo and active medication arms will be used as an indicator of problem worsening or improving. as one index of whether improvement is occurring. A higher problem rating indicates greater perceived difficulties.
Measured: Daily for 5 week days (Monday - Friday) of each trial week (8 weeks total)
Change in functional Impairment- between placebo and stimulant
Impairment resulting from ADHD symptoms. This scale contains the items that are most likely to represent the participant's target of treatment. The instrument uses a Likert scale such that any item rating 2 or 3 is clinically impaired. The scale is scored generating the total score. When defining impairment for DSM-IV, any domain with at least two items scored 2, one item scored 3 or a mean score >1.5 is impaired.
Measured: Daily for 5 week days (Monday - Friday) of each trial week (8 weeks total)
Difference in side effects during placebo and stimulant phase
Investigators will monitor side effects of the placebo and active medication using the Barkley Side Effects Rating Scale (17 symptoms; 0 = absent, severity rated from 1 to 9). Parent ratings of side effects for the drug and placebo conditions will be described using the mean total side effect rating for each condition.
Measured: Day 5 of each trial week (8 weeks total)
Trial feasibility - recruitment rate
Feasibility of the study (n-of-1 design) will be explored using trial recruitment rate across the trial from study start to study close. Investigators will calculate recruitment feasibility as the percentage of eligible participants agreeing to participate. A higher percentage will indicate greater participation.
Measured: End of 8 month active trial phase
Trial feasibility - completion rate
Feasibility of the study (n-of-1 design) will be explored using completion rates across the trial from study start to study close. Completion rate will be the percentage of enrolled participants who complete the trial. A higher percentage will indicate greater participation.
Measured: End of 8 month active trial phase
Compliance
Investigators will inspect participant medication diaries, to calculate treatment compliance. Non-compliance will be defined as missing more than one or more days of the active drug or placebo condition.
Measured: End of 8 month active trial phase
Assessment completion rate
Investigators will calculate the percentage of outcome assessments completed by each participant to examine assessment feasibility of the study design.
Measured: End of 8 month active trial phase
Data completion reason
Investigators will also examine reasons for incomplete outcome data.
Measured: End of 8 month active trial phase
Adverse events
Adverse events (AE's) will be coded using the, Medical Dictionary for Regulatory Activities (MedDRA), and calculated once each per participant. We will describe the total number of AE's across the trial.
Measured: End of 8 month active trial phase
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2021
- Study start14 Feb 2022
- Primary completionApr 2023 (estimated)
- Study completionJul 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fetal Alcohol Spectrum DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The N-of-1 trial has a four-period crossover design, comparing attention skills on active drug compared to placebo. The 8-week trial comprises four 2-week treatment blocks (each block consisting of 1 week active drug and 1 week placebo). Participants 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 is randomly allocated.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Monash Medical Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Monash University
- Responsible party
- Principal investigator, Alison Crichton, Monash Medical Centre
- Investigators
- Alison Crichton, PhD, Principal investigator, Monash Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04968522
- Sponsor's protocol ID
- RES-21-0000-248A
- Other IDs
- RES-21-0000-248A
- Acronym
- FASST
- Status last verified
- Dec 2022
- First submitted
- 2 Jun 2021
- Last updated
- 13 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Beginning 3 months following analysis and article publication, the following will be made available long-term for use by future researchers from a recognised research institution whose proposed use of the data has been ethically reviewed and approved by an independent committee and who accept Monash Health institutional conditions for access: * Group level data that underlie the results reported in this article after de-identification (text, tables, figures and appendices) * Trial protocol, PICF
Publications
Crichton A, Harris K, McGree JM, Nikles J, Anderson PJ, Williams K. Fetal alcohol spectrum disorder and attention deficit hyperactivity disorder stimulant trial in children: an N-of-1 pilot trial to compare stimulant to placebo (FASST): protocol. BMJ Open. 2024 Apr 17;14(4):e071266. doi: 10.1136/bmjopen-2022-071266.
PubMed 38631835
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Attention Management Trial for Children With FASD - a N-of-1 Control Trial of Prescribed Stimulants for ADHD in FASD
- ClinicalTrials.gov ID
- NCT04968522
- Acronym / sponsor ID
- FASST / RES-21-0000-248A
- Conditions
- Fetal Alcohol Spectrum Disorders
- Keywords
- Attention Deficit Hyperactivity Disorder, Stimulants, Trial, Attention
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Monash Medical CentreUniversity, hospital or other
- Collaborators
- Monash University
- Study start
- 14 Feb 2022 (actual)
- Primary completion
- Apr 2023 (estimated)
- Study completion
- Jul 2023 (estimated)
- First posted
- 20 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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.
- 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:
- Primary objective: Test ongoing effectiveness of stimulant medication in individual children with FASD on pharmacotherapy for ADHD symptomatology, using individual N-of-1 trials.
- 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- The N-of-1 trial has a four-period crossover design, comparing attention skills on active drug compared to placebo. The 8-week trial comprises four 2-week treatment blocks (each block consisting of 1 week active drug and 1 week placebo). Participants 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 is randomly allocated.
| Arm | Type | Receives |
|---|---|---|
| Placebo comparator 2 | Placebo comparator | Drug: PlaceboParticipants will be allocated a randomly allocated sequence of treatment. The randomisation will be in two-week pairs - so the order of treatment (A) and placebo (P) to be randomly assigned within each two-week cycle (over 8 weeks). Placebo will be matched in dose to their stimulant dose at enrolment to the trial as determined and titrated by their primary paediatrician. This dose will remain constant for the course of the trial (8 weeks). Placebo will be orally administered, unless this is not possible for clinical reasons. |
| Stimulant | Experimental | Drug: Methylphenidate Hydrochloride, Drug: Methylphenidate Hydrochloride 18 MG, Drug: Dexamphetamine sulfateThe stimulants used in the trial are commercially available and will be used in accordance with the approved labelling. Participants must be on a stable dose of stimulant medication for at last 1 month prior to the study. The dose is individualized and titrated by treating primary paediatrician. This will represent the starting dose for the trial, and this will remain stable through the course of the 8-week trial. 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. Based on pilot data from this group, psychostimulant medications prescribed in this population may include: * Methylphenidate IR * Methylphenidate LA * Dexamphetamine Children will take the required number of capsules to match the total prescribed dose (e.g. 30mg Ritalin LA is 3x10mg capsules). |
Who may qualify
- Ages
- 4 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Is between the ages of 4 - 18 years at the time of randomization.
- Meet diagnostic criteria for FASD or at risk of FASD according to the Australian Guide to the diagnosis of FASD.
- Is a patient of VicFAS or Developmental Paediatrics (Monash Health).
- Has a diagnosis of ADHD according to the DMS-IV criteria.
- Be on a stimulant medication for treatment of ADHD symptoms.
Key exclusion criteria (13 listed)
- Inability to read or speak sufficient English for either child or parent/guardian to complete assessment tasks.
- Be on a medication for treatment of ADHD symptoms that is a medication other than stimulants as a primary treatment for ADHD.
- Allergy/sensitivity to Starcke 1500 (Maize Starch and Pregelatinised Maize Starch).
- Unable to swallow capsules.
- Intracranial symptoms or pathology such as epilepsy, hydrocephalus, diagnosed traumatic. brain injury or progressive intracranial tumours that may impact cognitive and behavioural function (children with asymptomatic or static lesions will be eligible).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methylphenidate HydrochlorideAlso: Ritalin 10 tabletsThis 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 | Stimulant |
| PlaceboThe 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 | Placebo comparator 2 |
| Methylphenidate hydrochlorideAlso: Ritalin LA Long acting capsulesThis 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 | Stimulant |
| Methylphenidate Hydrochloride 18 MGAlso: ConcertaThis 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 | Stimulant |
| Dexamphetamine sulfateAlso: Aspen Dexamfetamine TabletsThis 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. | Drug | Stimulant |
Primary outcome
Change in ADHD symptoms - teacher report - between placebo and stimulant
Time frame: Daily for 5 week days (Monday - Friday) of each trial week (8 weeks total)
ADHD symptoms will be measured using the Conners 3rd Edition-Teacher (Conners 3-T), for 6-18 year old's and the Conners Early Childhood teachers/childcare providers (full length) form for participants 2-6 years. Each item is rated on a Likert scale from 0 to 3 (0=never or rarely; 1=sometimes; 2=often; 3=very often). Test- retest values for the Conners scales indicate excellent temporal stability (ranging from .73 to 1.00). The T-score is norm referenced, with a mean of 50. The average range falls within one standard deviation of the mean (i.e., between 40 and 59). A higher score indicates more elevated symptoms. T score Guideline 70+Very Elevated Score 65-69 Elevated Score 40-59 Average score 60-64 High average score < 40 Low score. Investigators will examine Inattentive and Hyperactivity/Impulsivity Symptom Scales. Symptoms indicated for each subscale are summed to get total.
Change in ADHD symptoms - parent report - between placebo and stimulant
Time frame: Daily for 5 week days (Monday - Friday) of each trial week (8 weeks total)
ADHD symptoms will be measured using the Conners 3rd Edition-Parent (Conners 3-P), for 6-18 year old's and the Conners Early Childhood parent (full length) form for participants 2-6 years. Each item is rated on a Likert scale from 0 to 3 (0=never or rarely; 1=sometimes; 2=often; 3=very often). Test- retest values for the Conners scales indicate excellent temporal stability (ranging from .73 to 1.00). The T-score is norm referenced. The average range falls within one standard deviation of the mean (i.e., between 40 and 59). A higher score indicates more elevated symptoms. T score Guideline 70+Very Elevated Score 65-69 Elevated Score 40-59 Average score 60-64 High average score < 40 Low score. Investigators will examine Inattentive and Hyperactivity/Impulsivity Symptom Scales. Symptoms indicated for each subscale are summed to get the total.
Change in spatial working memory - between placebo and stimulant
Time frame: Day 3 of each trial week (8 weeks total)
Spatial Working Memory (SWM) task from the Cambridge Neuropsychological Test Automated Battery. SWM is a component of cognitive executive function which is measured by SWM task of CANTAB between the errors. The ability to retain spatial information and manipulate remembered items in working memory will be measured with the SWM task of CANTAB which is self-ordered and assesses the individual's ability to strategise. Between search errors will be analysed. Scores are raw scores, with no normative data available. Higher error score indicated poorer performance. Scale does not have a maximum range.
Change in Visual Information Processing - between placebo and stimulant
Time frame: Day 3 of each trial week (8 weeks total)
Rapid Visual Information Processing (SOC) from Cantab. SOC Stockings of Cambridge (SOC) is a test of spatial planning that requires individuals to use problem-solving strategies to match two sets of stimuli. The participant must move the balls in the bottom display to copy the pattern shown in the top display. The balls are moved one at a time by selecting the required ball, then selecting the position to which it should be moved. The participant is instructed to make as few moves as possible to match the two pattern. The outcome measure of this subtest is the number of problems completed, regardless of whether the maximum moves limit was reached on any problem.
9 secondary outcomes
Change in child problem behaviour rating- between placebo and stimulant
Time frame: Daily for 5 week days (Monday - Friday) of each trial week (8 weeks total)
Change in functional Impairment- between placebo and stimulant
Time frame: Daily for 5 week days (Monday - Friday) of each trial week (8 weeks total)
Difference in side effects during placebo and stimulant phase
Time frame: Day 5 of each trial week (8 weeks total)
Trial feasibility - recruitment rate
Time frame: End of 8 month active trial phase
Trial feasibility - completion rate
Time frame: End of 8 month active trial phase
Compliance
Time frame: End of 8 month active trial phase
Assessment completion rate
Time frame: End of 8 month active trial phase
Data completion reason
Time frame: End of 8 month active trial phase
Adverse events
Time frame: End of 8 month active trial phase
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2022.
- Derived from this study: PubMed 38631835Crichton A, Harris K, McGree JM, Nikles J, Anderson PJ, Williams K. Fetal alcohol spectrum disorder and attention deficit hyperactivity disorder stimulant trial in children: an N-of-1 pilot trial to compare stimulant to placebo (FASST): protocol. BMJ Open. 2024 Apr 17;14(4):e071266. doi: 10.1136/bmjopen-2022-071266.
- Individual participant dataSharing planned: Undecided. Beginning 3 months following analysis and article publication, the following will be made available long-term for use by future researchers from a recognised research institution whose proposed use of the data has been ethically reviewed and approved by an independent committee and who accept Monash Health institutional conditions for access: * Group level data that underlie the results reported in this article after de-identification (text, tables, figures and appendices) * Trial protocol, PICF
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alison Crichton, PhD principal investigator
Monash Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Methylphenidate Hydrochloride, Methylphenidate Hydrochloride 18 MG and Dexamphetamine sulfate in people with Fetal Alcohol Spectrum Disorders, run by Monash Medical Centre at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alison Crichton, PhD (0428214717, ali.crichton@monashhealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in ADHD symptoms - teacher report - between placebo and stimulant (time frame: Daily for 5 week days (Monday - Friday) of each trial week (8 weeks total)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04968522, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2022.