Novel Approach to Stimulant Induced Weight Suppression and Its Impact on Growth
Condition: ADHD; Growth
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): behavior therapy; Extended release (ER) methylphenidate product; monitoring; drug holiday; caloric supplement
Intervention type(s): Behavioral; Drug; Other; Other; Dietary Supplement
Intervention description(s): combination of individual and group parent training plus school consultation; medication to be taken daily for duration of study unless assigned to weight promotion arm; monthly weight, height and BMI checks; switch from seven day a week dosing to medication only on school days; continue current ADHD regimen and add one 8oz liquid caloric supplement at night
Other intervention name(s): behavior modification; Concerta, OROS-MPH; Central Nervous Systemt (CNS) stimulants; monitoring arm; Ritalin based product, CNS stimulants
Intervention MeSH terms: Methylphenidate; Central Nervous System Stimulants
Allocation: Randomized
Intervention model: Parallel Assignment
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)
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: ADHD; growth; BMI; stimulant medication