Novel Approach to Stimulant Induced Weight Suppression and Its Impact on Growth

NCT01109849 | Completed Phase 3 Results DMC

• 1 other identifier: R01MH083692
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 1

Brief Summary

Previous NIH funded Attention Deficit Hyperactivity Disorder (ADHD) trials in children found that daily stimulant therapy produced sustained growth deficits. However, no federally funded studies have examined the growth suppression associated with modern once a day stimulant medications. Therefore, this study will precisely estimate the risks of stimulant induced growth suppression (SIGS), examine the underlying mechanisms and develop treatments for it. While drug holidays and caloric supplementation are two common treatments for SIGS, there has been little systematic investigation of either. It is unknown if they are effective or feasible. Therefore, using a randomized adaptive design, we will evaluate the efficacy and feasibility of these two practices vs. routine monitoring of growth in 180 prepubertal children with ADHD. An additional 50 subjects will be treated solely with behavioral therapies to evaluate for growth abnormalities associated with ADHD. The study will assess will the risk of SIGS with ER stimulants and the underlying mechanisms while providing evidenced-based treatments for its management.

Conditions

ADHD; Growth

Keywords

ADHD; growth; BMI; stimulant medication

Outcome Measures

Primary Outcomes (1)

• Change Score for Z-height Baseline to Endpoint

  The primary endpoint will be change in z-height at month 30 which is study endpoint. Measured as a zscore with more negative units reflecting smaller incremental height gain. Z units used to account for differences between groups in gender and age with both impact height at a fixed time.

  month 30 or last assessment point

Secondary Outcomes (11)

• Change Score for z Weight

  baseline to month 30 or to last assessment point

• Change in zBody Mass Index (BMI)

  baseline to month 30 or last assessment point

• Treatment Adherence for Caloric Supplement

  from entry to exit of caloric supplement arm

• ADHD Symptoms- Parent Rated

  at month 30 or last collected assessment point

• Change Score for Zheight Months 0 to 6

  baseline to month 6

Study Arms (5)

weight recovery treatment- monitoring

ACTIVE COMPARATOR

Subjects in either the behavior therapy arm or the medication arm will be assigned to one of 3 treatments if subject does not meet projected BMI goals. In the monitoring arm , participants will continue on their ER stimulant 7 days a week and have their weight, height and BMI checked monthly.

Other: monitoring

behavior therapy

ACTIVE COMPARATOR

10 week basic parent training, advanced 8 week parent training course. monthly boosters, option for individual parent training sessions, school consultant assigned to each subject

Behavioral: behavior therapy

ER stimulant

EXPERIMENTAL

daily use of 12 hour extended release methylphenidate product

Drug: Extended release (ER) methylphenidate product

weight recovery treatment- caloric supplement

EXPERIMENTAL

Subjects in either the behavior therapy arm or the medication arm will be assigned to one of 3 treatments if subject does not meet projected BMI goals. In the caloric supplement arm, participants will continue on their ER stimulant 7 days a week, have their weight, height and BMI checked monthly and be prescribed a 150 kcal caloric supplement to be consumed every evening.

Dietary Supplement: caloric supplement

weight recovery treatment- drug holiday

EXPERIMENTAL

Subjects in either the behavior therapy arm or the medication arm will be assigned to one of 3 treatments if subject does not meet projected BMI goals. In the drug holiday arm, participants will only take their ER stimulant on school days a week and have their weight, height and BMI checked monthly.

Other: drug holiday

Interventions

behavior therapy BEHAVIORAL

combination of individual and group parent training plus school consultation

Also known as: behavior modification

behavior therapy

Extended release (ER) methylphenidate product DRUG

medication to be taken daily for duration of study unless assigned to weight promotion arm

Also known as: Concerta, OROS-MPH, Central Nervous Systemt (CNS) stimulants

ER stimulant

monitoring OTHER

monthly weight, height and BMI checks

Also known as: monitoring arm

weight recovery treatment- monitoring

drug holiday OTHER

switch from seven day a week dosing to medication only on school days

Also known as: Ritalin based product, CNS stimulants

weight recovery treatment- drug holiday

caloric supplement DIETARY_SUPPLEMENT

continue current ADHD regimen and add one 8oz liquid caloric supplement at night

weight recovery treatment- caloric supplement

Eligibility Criteria

• Age: 5 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• children meeting criteria for any subtype of ADHD between the ages of 5-12 who are stimulant naive

You may not qualify if:

• Children who meet any of the following criteria will not be eligible to participate in this study:
• children with a Full Scale Intelligence Quotient (I below 70 as children with IQs less than this would likely not benefit from the behavior therapy intervention
• not in full time school or less than 5 or older than 12 years at the time of the screening visit
• children who have a history of seizures or other neurological problems and are taking medication to prevent seizures as stimulants could worsen seizures
• children with a history of other medical problems for whom psychostimulant treatment may involve considerable risk including cardiac arrhythmias, hypertension, Tourette's Disorder or history of severe tic exacerbations secondary to stimulant exposure
• children with a history of other medical problems that could impact appetite or weight such as hypothyroidism, diabetes mellitus, liver or renal disease. Also, children using prescription medication that can significantly impact appetite or weight are excluded
• children with a childhood history or diagnosis of any of the following mental health disorders: pervasive developmental disorder, schizophrenia or other psychotic disorders, bipolar disorder, post traumatic stress disorder, major depression with serious suicidal thoughts or an eating disorder as stimulants are not safe and effective treatments for these conditions, and these diseases could affect eating habits
• children whose Body Mass Index is very low (too light for safe use of stimulant medication) or is too high (overweight so not suitable for weight promotion treatments)
• children allergic to milk proteins as they are in the caloric supplement (lactose intolerance okay)
• children previously treated with stimulant medications for more than 30 days as this study is focusing on children who have never used stimulant medication before.

Sponsors & Collaborators

• Florida International University: lead

Study Sites (1)

Center for Children and Families, Florida International University

Miami, Florida, 33199, United States

Location

Related Publications (3)

• Waxmonsky JG, Pelham WE 3rd, Baweja R, Hale D, Pelham WE Jr. Predictors of Changes in Height, Weight, and Body Mass Index After Initiation of Central Nervous System Stimulants in Children with Attention Deficit Hyperactivity Disorder. J Pediatr. 2022 Feb;241:115-125.e2. doi: 10.1016/j.jpeds.2021.09.030. Epub 2021 Sep 25.

  PMID: 34571023 DERIVED

• Baweja R, Waschbusch DA, Pelham WE 3rd, Pelham WE Jr, Waxmonsky JG. The Impact of Persistent Irritability on the Medication Treatment of Paediatric Attention Deficit Hyperactivity Disorder. Front Psychiatry. 2021 Jul 21;12:699687. doi: 10.3389/fpsyt.2021.699687. eCollection 2021.

  PMID: 34366928 DERIVED

• Waxmonsky JG, Pelham WE 3rd, Campa A, Waschbusch DA, Li T, Marshall R, Babocsai L, Humphery H, Gnagy E, Swanson J, Hanc T, Fallahazad N, Pelham WE Jr. A Randomized Controlled Trial of Interventions for Growth Suppression in Children With Attention-Deficit/Hyperactivity Disorder Treated With Central Nervous System Stimulants. J Am Acad Child Adolesc Psychiatry. 2020 Dec;59(12):1330-1341. doi: 10.1016/j.jaac.2019.08.472. Epub 2019 Aug 29.

  PMID: 31473291 DERIVED

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Behavior Therapy; Methylphenidate; Nurse Clinicians; Central Nervous System Stimulants; Treatment Interruption

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Psychotherapy; Behavioral Disciplines and Activities; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nurse Specialists; Nurses; Health Personnel; Health Care Facilities Workforce and Services; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Central Nervous System Agents; Therapeutic Uses; Treatment Adherence and Compliance; Attitude to Health; Delivery of Health Care; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: James Waxmonsky MD
• Organization: Penn State College of Medicine

jwaxmonsky@pennstatehealth.psu.edu

7175318646

Study Officials

• James G Waxmonsky, MD

  Florida International University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: initial randomization to behavior or extended release stimulant (ER stimulant) arms. Participants in either arm meting criteria for a weight recovery intervention (based on change in zBMI) will be adaptively randomized to one of three weight recovery arms (Monitoring, Drug Holiday, Caloric Supplementation)

Study Record Dates

• First Submitted: April 21, 2010
• First Posted: April 23, 2010
• Study Start: November 1, 2010
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: July 14, 2017
• Results First Posted: July 14, 2017

Record last verified: 2017-06

Locations

US (1)