ADHD Medication and Predictors of Treatment Outcome (ADAPT)

• ClinicalTrials.gov Identifier: NCT02136147
• Recruitment Status: Active, not recruiting
• First Posted: May 12, 2014
• Last Update Posted: October 8, 2021
• Sponsor: Karolinska Institutet
• Information provided by (Responsible Party): Linda Halldner Henriksson, Karolinska Institutet

Study Description

Brief Summary:

ADHD medication of children and adolescents is becoming increasingly common. Clinical experience and scientific studies have proven that approximately 30% of children/adolescents with ADHD do not benefit from this treatment. However, there is insufficient knowledge about who these children are. All children and adolescents, who start treatment with ADHD medication at public Child and Adolescent Psychiatry units in Stockholm, on Gotland, an in Västerbotten, will be asked to participate in the study. The investigators intend to monitor the patients´clinical symptoms and possible side-effects after treatment start. The investigators will collect background information and saliva samples from the patient and his/her parents to be able to study if there are any genetic (hereditary) or other markers that can predict positive or negative outcomes of the ADHD medication. With this information, the investigators aim at, to a greater extent, be able to individualize treatment choices for children and adolescents with ADHD without unnecessary, costly and possibly unfavorable treatment attempts.

Condition or disease	Intervention/treatment
Attention Deficit Disorder With Hyperactivity (ADHD)	Drug: methylphenidate medication; Drug: atomoxetine medication; Drug: lisdexamphetamine medication; Drug: guanfacine medication

Detailed Description:

The specific aims for the ADAPT study are:

1. Investigate if certain gene polymorphisms are associated with poor effect of ADHD drugs (non-responders).
2. Investigate if other biologically, phenotypic or psychosocial factors are associated with poor effect of ADHD drugs (non-responders).
3. Investigate if the frequency of side-effects of ADHD drugs differs between children with different genotypes.
4. Investigate if the frequency of side-effects of ADHD drugs differs between children with different phenotypic and/or psychosocial factors

Method:

This study has a naturalistic design. The aim is to map all new treatments with ADHD drugs at all 13 public BUP units in Stockholm County, one BUP unit on Gotland, and three BUP units in Västerbotten Region. The participation means that medication is initiated as planned in normal clinical practice by the child´s ordinary physician, and beyond this only means a somewhat denser and more structured follow-up. In addition, the investigators will ask for saliva samples from the patient and his/her parents. The investigators aim at including at least 1000 individuals in total in the study.

Part of the data will be collected via the national Quality Register for ADHD Treatment Follow-up (BUSA), which has approved security procedures approved by the Swedish Data Inspection Board.

Case report forms are computerized and separate from the database registry for collected study data. The database and detailed variable lists are constructed in collaboration with professional database managers.

Standard Operation Procedures are designed in collaboration by project coordinator, study nurse and principal investigator, and may be revised after pilot phase.

Collected samples will be stored at KI biobank.

Data analysis:

1. To judge if the patient is a responder to ADHD drugs the SNAP-IV rating of ADHD symptoms (before and after medication start) is used. The patients who at 3 months have an at least 40% reduction in SNAP-IV score are reckoned "responders" and those who at the same time point have a less than 20% change in SNAP-IV score are reckoned "non-responders". Differences between the groups will be analyzed with logistic regression, with responder status as depending variable, and genotype and the other risk markers (biological, phenotypic, and psychosocial markers) as independent variables after correction for symptoms at baseline. Even a 50% drop-out rate will (i.e. 1000 out of estimated 2000 eligible individuals) give a 98% power to identify a 49% increase in non-responder proportion for a specific genotype.
2. Concomitantly, the outcome in side-effects, heart rate, blood pressure, weight (z-score) and length (z-score) will be analyzed with linear regression with the same independent variables.
3. The analyses are performed separately for each ADHD drug.
4. There are significantly more boys than girls (about 4:1) with ADHD. Given the sex difference in prevalence it is obvious to also include sex as a covariate in our analyses of treatment outcome.
5. Missing data will be treated according to the principles of complete case and multiple imputation.

Study Design

• Study Type: Observational [Patient Registry]
• Actual Enrollment: 632 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Target Follow-Up Duration: 12 Months
• Official Title: Naturalistic Study of ADHD Medication and Predictors of Treatment Outcome
• Actual Study Start Date: June 2015
• Actual Primary Completion Date: July 2021
• Estimated Study Completion Date: July 2022

Groups and Cohorts

Group/Cohort	Intervention/treatment
Children with ADHD medication; Identified responders and non-responders in children/adolescents starting medication for treatment of ADHD in public child and adolescent psychiatric services in Stockholm, on Gotland, and in Västerbotten.	Drug: methylphenidate medication; Other Names: N06BA04; Concerta; Ritalin; Equasym; Medikinet; Drug: atomoxetine medication; Other Names: N06BA09; Strattera; Drug: lisdexamphetamine medication; Other Names: N06BA12; Elvanse; Drug: guanfacine medication; Other Names: C02AC02; Intuniv
Lisdexamphetamine medication; Identified responders and non-responders in children/adolescents starting medication with lisdexamphetamine in public child and adolescent psychiatric services in Stockholm and on Gotland.	Drug: lisdexamphetamine medication; Other Names: N06BA12; Elvanse
Atomoxetine medication; Identified responders and non-responders in children/adolescents starting medication with atomoxetine in public child and adolescent psychiatric services in Stockholm and on Gotland.	Drug: atomoxetine medication; Other Names: N06BA09; Strattera
Methylphenidate medication; Identified responders and non-responders in children/adolescents starting medication with methylphenidate in public child and adolescent psychiatric services in Stockholm and on Gotland.	Drug: methylphenidate medication; Other Names: N06BA04; Concerta; Ritalin; Equasym; Medikinet
Guanfacine medication; Identified responders and non-responders in children/adolescents starting medication with guanfacine in public child and adolescent psychiatric services in Stockholm and on Gotland.	Drug: guanfacine medication; Other Names: C02AC02; Intuniv

Outcome Measures

Primary Outcome Measures :

1. change in SNAP-IV Teacher and Parent rating scale (Swanson, Nolan and Pelham ADHD Rating Scale) [ Time Frame: at 3 months follow-up ]
   ADHD symptoms
2. change in P-SEC (Pediatric Side Effects Checklist) [ Time Frame: at 3 months follow-up ]
   Side-effect measure

Secondary Outcome Measures :

1. change in C-GAS (Children´s global assessment scale) [ Time Frame: at 12 months follow-up ]
   global functioning measure
2. change in CGI-S (Clinical Global Impression- of Severity) [ Time Frame: at 12 months follow-up ]
   disease severity
3. change in SNAP-IV Teacher and Parent rating scale [ Time Frame: at 1 month follow-up ]
   ADHD symptoms
4. change in SNAP-IV Teacher and Parent rating scale [ Time Frame: at 6 months follow-up ]
   ADHD symptoms
5. change in SNAP-IV Teacher and Parent rating scale [ Time Frame: at 12 months follow-up ]
   ADHD symptoms
6. change in P-SEC (Pediatric Side Effects Checklist) [ Time Frame: at 1 month follow-up ]
   side effect measure
7. change in P-SEC (Pediatric Side Effects Checklist) [ Time Frame: at 6 months follow-up ]
   side effect measure
8. change in P-SEC (Pediatric Side Effects Checklist) [ Time Frame: at 12 months follow-up ]
   side effect measure
9. change in Spence Children's Anxiety Scale (SCAS) [ Time Frame: at 1 month follow-up ]
   symptoms of anxiety
10. change in Spence Children's Anxiety Scale (SCAS) [ Time Frame: at 3 months follow-up ]
    symptoms of anxiety
11. change in Spence Children's Anxiety Scale (SCAS) [ Time Frame: at 6 months follow-up ]
    symptoms of anxiety
12. change in Spence Children's Anxiety Scale (SCAS) [ Time Frame: at 12 months follow-up ]
    symptoms of anxiety
13. change in heart rate [ Time Frame: at 1 month follow-up ]
14. change in heart rate [ Time Frame: at 3 months follow-up ]
15. change in heart rate [ Time Frame: at 6 months follow-up ]
16. change in heart rate [ Time Frame: at 12 months follow-up ]
17. change in systolic blood pressure [ Time Frame: at 1 month follow-up ]
18. change in systolic blood pressure [ Time Frame: at 3 months follow-up ]
19. change in systolic blood pressure [ Time Frame: at 6 months follow-up ]
20. change in systolic blood pressure [ Time Frame: at 12 months follow-up ]
21. change in diastolic blood pressure [ Time Frame: at 1 month follow-up ]
22. change in diastolic blood pressure [ Time Frame: at 3 months follow-up ]
23. change in diastolic blood pressure [ Time Frame: at 6 months follow-up ]
24. change in diastolic blood pressure [ Time Frame: at 12 months follow-up ]
25. change in weight z-score [ Time Frame: at 1 month follow-up ]
26. change in weight z-score [ Time Frame: at 3 months follow-up ]
27. change in weight z-score [ Time Frame: at 6 months follow-up ]
28. change in weight z-score [ Time Frame: at 12 months follow-up ]
29. change in height z-score [ Time Frame: at 6 months follow-up ]
30. change in height z-score [ Time Frame: at 12 months follow-up ]
31. change in Autism Spectrum Screening Questionnaire (ASSQ) score [ Time Frame: at 3 months follow-up ]
    symptoms of autism
32. change in Autism Spectrum Screening Questionnaire (ASSQ) score [ Time Frame: at 1 months follow-up ]
    symptoms of autism
33. change in Autism Spectrum Screening Questionnaire (ASSQ) score [ Time Frame: at 6 months follow-up ]
    symptoms of autism
34. change in Autism Spectrum Screening Questionnaire (ASSQ) score [ Time Frame: at 12 months follow-up ]
    symptoms of autism

Other Outcome Measures:

1. change in self-harm frequency [ Time Frame: at 12 months follow-up ]
   change in self-harm frequency behavior as noted in the quality register BUSA
2. change in suicide attempt frequency [ Time Frame: at 12 months follow-up ]
   change in suicide attempt frequency as reported in quality register BUSA

Biospecimen Retention:   Samples With DNA

Saliva

Eligibility Criteria

• Ages Eligible for Study: 6 Years to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

All children/adolescents starting ADHD medication at the public child and adolescent psychiatry services in Stockholm and on Gotland

Criteria

Inclusion Criteria:

• Clinical diagnosis of ADHD
• Starting medication against ADHD symptoms with atomoxetine, methylphenidate, lisdexamphetamine, or guanfacine

Exclusion Criteria: Any medication against ADHD the last 3 months

Contacts and Locations

Locations

Sweden

Division for Child and Adolescent Psychiatry in Stockholm

Stockholm, Stockholm County, Sweden

Sponsors and Collaborators

Karolinska Institutet

More Information

Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lilja MM, Sandblom E, Lichtenstein P, Serlachius E, Hellner C, Bhagia J, Halldner L. The effect of autistic traits on response to and side-effects of pharmacological ADHD treatment in children with ADHD: results from a prospective clinical cohort. J Neurodev Disord. 2022 Mar 6;14(1):17. doi: 10.1186/s11689-022-09424-2.

• Responsible Party: Linda Halldner Henriksson, MD, PhD, Karolinska Institutet
• ClinicalTrials.gov Identifier: NCT02136147
• Other Study ID Numbers: ADAPT; LS 1110-1339 ( Other Grant/Funding Number: ALF/PPG ); SLS-309701 ( Other Grant/Funding Number: Stiftelsen Söderström-Königska sjukhemmet )
• First Posted: May 12, 2014
• Last Update Posted: October 8, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Linda Halldner Henriksson, Karolinska Institutet:

Attention Deficit Disorder with Hyperactivity; Neuropsychiatry; Drug therapy; Pharmacogenetics; Child Psychiatry

Additional relevant MeSH terms:

Hyperkinesis; Attention Deficit Disorder with Hyperactivity; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Guanfacine; Methylphenidate; Lisdexamfetamine Dimesylate; Atomoxetine Hydrochloride; Central Nervous System Stimulants; Physiological Effects of Drugs; Dopamine Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Neurotransmitter Agents; Adrenergic Uptake Inhibitors; Adrenergic Agents; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists