FASST - Fetal Alcohol Spectrum Stimulant Trial

NCT04968522 | Unknown Phase 4 DMC FDA Drug

• 1 other identifier: RES-21-0000-248A
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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. 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. 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. 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.

Conditions

Fetal Alcohol Spectrum Disorders

Keywords

Attention Deficit Hyperactivity Disorder; Stimulants; Trial; Attention

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  Day 3 of each trial week (8 weeks total)

Secondary Outcomes (9)

• Change in child problem behaviour rating- between placebo and stimulant

  Daily for 5 week days (Monday - Friday) of each trial week (8 weeks total)

• Change in functional Impairment- between placebo and stimulant

  Daily for 5 week days (Monday - Friday) of each trial week (8 weeks total)

• Difference in side effects during placebo and stimulant phase

  Day 5 of each trial week (8 weeks total)

• Trial feasibility - recruitment rate

  End of 8 month active trial phase

• Trial feasibility - completion rate

  End of 8 month active trial phase

Other Outcomes (10)

• Rate of change of prescribed stimulant

  End of trial (8 weeks)

• Attention Deficit Hyperactivity Disorder subtype classification

  Baseline

• Attention factor 1 (selective)

  Baseline

Study Arms (2)

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.

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).

Drug: Methylphenidate Hydrochloride; Drug: Methylphenidate Hydrochloride 18 MG; Drug: Dexamphetamine sulfate

Interventions

Methylphenidate hydrochloride DRUG

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.

Also known as: Ritalin 10 tablets

Stimulant

Placebo DRUG

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.

Placebo comparator 2

Methylphenidate Hydrochloride 18 MG DRUG

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.

Also known as: Concerta

Stimulant

Dexamphetamine sulfate DRUG

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.

Also known as: Aspen Dexamfetamine Tablets

Stimulant

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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'.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Monash Medical Centre: lead
• Monash University: collaborator

Study Sites (1)

Monash Health

Clayton, Victoria, 3168, Australia

RECRUITING

Related Publications (1)

• 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.

  PMID: 38631835 DERIVED

MeSH Terms

Conditions

Fetal Alcohol Spectrum Disorders; Attention Deficit Disorder with Hyperactivity

Interventions

Methylphenidate; Amphetamine

Condition Hierarchy (Ancestors)

Fetal Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Amphetamines; Phenethylamines; Ethylamines; Amines

Study Officials

• Alison Crichton, PhD

  Monash Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alison Crichton, PhD

CONTACT

0428214717; ali.crichton@monashhealth.org

Katrina Williams, PhD

CONTACT

- +61 3 8572 2602; katrina.williams@monash.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The order of medications (placebo/active drug) will be masked to the participant, assessors and investigator. At the end of the trial, the order of medications will be unmasked, and compared with the parent and teachers' observations of the child's behaviour.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: June 2, 2021
• First Posted: July 20, 2021
• Study Start: February 14, 2022
• Primary Completion: April 1, 2023
• Study Completion: July 1, 2023
• Last Updated: December 13, 2022

Record last verified: 2022-12

Locations

AU (1)