Clinical trial NCT01109849: Novel Approach to Stimulant Induced Weight Suppression and Its Impact on Growth
Official title: Novel Approach to Stimulant Induced Weight Suppression and Its Impact on Growth
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: ADHD
Growth
Keywords: ADHD
growth
BMI
stimulant medication
Lead sponsor: Florida International University
Sponsor class: OTHER
First posted: 2010-04-23
Enrollment: 230
Sex: ALL
Minimum age (years): 5
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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)
Primary purpose: TREATMENT

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.

Detailed description: The study will consist of 4 parts:

1. Screening assessment to determine if a child has ADHD and would be a good candidate to have their ADHD treated with an extended release (ER) stimulant medication. If the answer to step one is yes, then the child will be randomly assigned to receive either medication treatment with an extended release MPH product (OROS MPH). 78% of children with start with this option with 22% assigned to behavioral therapy/counseling treatments for ADHD. There will be no placebo treatments used in this study. All children must be between the ages of 5 and 12 and never have taken stimulant medications for ADHD for more than one week to be eligible for the study.
2. Initial Treatment Phase: The dose of the assigned treatment option will be gradually adjusted over the course of the first 3 months until the child's ADHD is well controlled. If the child is assigned to medication, he/she will start with a low dose of the ER MPH product, and it will be gradually increased until his/her ADHD is in good control. Children assigned to medication will be asked to take it every day of the week for at least the first 6 months. Children assigned to behavior therapy will be asked to avoid using medication for the first 6 months of the study. After month 6 if the first treatment is not effective, the child will be given the chance to try the other option. If any treatment is causing a concerning side effect, he/she can stop taking it at any time and we will provide him/her with other treatment options as part of the study.
3. Ongoing Treatment Phase: We will continue to provide these ADHD treatments for a total of 30 months (2 1/2 years). The dose or type of therapy may be adjusted if needed. The child will be monitored every 1-3 months over this time span. Monitoring includes doctor visits to assess growth and side effects of medication, regular contact with his/her teacher to assess function at school and with you to assess function at home. In total, the child will receive study treatments for approximately 30 months and will be required to come to our center for a minimum of 18 follow up visits over this time. The average visit should take 30 minutes or less.
4. Weight Recovery Phase: Any child whose body mass index or BMI declines by a concerning amount will be randomly assigned to receive 1 of 3 weight promotion treatments to stabilize his/her BMI in order to see if this prevents suppression of height (keeps them growing to be as tall as they should be). We do not expect children assigned to the behavior therapy arm to need these treatments, but the identical weight promotion treatments will be available for children in this group if the need arises.

A) Extra monitoring: A doctor will check the child's growth every month (instead of every 3 months) until his/her BMI has returned to normal.The child will stay on the current daily dose of medication or behavior therapy.

B) Caloric supplementation: Parents will be provided with a flavored calorie drink to give to your child every night and continue on the same daily dose and frequency of medication or behavior therapy. The child will have their growth monitored monthly by a study doctor.

C) Drug Holiday: Participants will now only take medication on school days. Children assigned to behavior therapy will not participate in this treatment as they are not taking any study medication. The child will have their growth monitored monthly by a study doctor.

Once the child's weight recovers, these extra treatments will end and he/she will return to the prior medication treatment (medication7 days a week or behavior therapy) in step 3 and to every 3 month growth assessments. Any time the child's BMI declines again, the extra treatments will restart again.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change Score for Z-height Baseline to Endpoint
timeFrame: month 30 or last assessment point
Secondary outcomes:
measure: Change Score for z Weight
timeFrame: baseline to month 30 or to last assessment point
measure: Change in zBody Mass Index (BMI)
timeFrame: baseline to month 30 or last assessment point
measure: Treatment Adherence for Caloric Supplement
timeFrame: from entry to exit of caloric supplement arm
measure: ADHD Symptoms- Parent Rated
timeFrame: at month 30 or last collected assessment point
measure: Change Score for Zheight Months 0 to 6
timeFrame: baseline to month 6
measure: ADHD Symptoms- Teacher Rated
timeFrame: month 30 or last assessment point
measure: Medication Adherence
timeFrame: denominator is number of days in study for which study med was prescribed
measure: Number of Behavior Therapy Sessions
timeFrame: months 0 through 30
measure: Change in Height z Score During Weight Recovery Phase (Second Randomization)
timeFrame: between 1 month and 24 months
measure: Change in Weight z Score During Weight Recovery Phase (Second Randomization)
timeFrame: 1 to 24 months duration
measure: Change in Zscore for BMI During Weight Recovery Phase (Second Randomization)
timeFrame: between 1 month and 24 months
Other outcomes:
Locations:
city: Miami
country: United States
facility: Center for Children and Families, Florida International University
state: Florida
Study officials:
affiliation: Florida International University
name: James G Waxmonsky, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.