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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Florida International University
ClinicalTrials.gov Identifier:
NCT01109849
First received: April 21, 2010
Last updated: April 15, 2014
Last verified: April 2014
  Purpose

Previous NIH funded 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.


Condition Intervention Phase
ADHD
Growth
Behavioral: behavioral therapy
Drug: 12 hour methylphenidate product
Behavioral: increased monitoring of growth
Drug: drug holiday
Dietary Supplement: caloric supplement
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Novel Approach to Stimulant Induced Weight Suppression and Its Impact on Growth

Resource links provided by NLM:


Further study details as provided by Florida International University:

Primary Outcome Measures:
  • height [ Time Frame: month 30 ] [ Designated as safety issue: Yes ]
    The primary endpoint will be height at month 30 which is study endpoint.


Secondary Outcome Measures:
  • weight [ Time Frame: month 30 ] [ Designated as safety issue: Yes ]
    will be assessed at endpoint (month 30) as well as at weeks 0, 2, 4,6, 8, 10, 12, 16, 20, 24, and months 9, 12, 15, 18, 21, 24, 27. Subjects in the weight promotion arms will have their weight measured monthly in addition to these times.

  • Body Mass Index (BMI) [ Time Frame: at month 30 ] [ Designated as safety issue: Yes ]
    BMI will be calculated at endpoint (month 30) and at weeks 0, 2, 4,6, 8, 10, 12, 16, 20, 24, and months 9, 12, 15, 18, 21, 24, 27. Subjects in the weight promotion arms will have their BMI calculated monthly in addition to these times.

  • treatment adherence [ Time Frame: at month 30 ] [ Designated as safety issue: Yes ]
    will measure number of days medication and caloric supplement are taken as well as attendance at behavioral therapies

  • ADHD symptoms- parent rated [ Time Frame: at month 30 ] [ Designated as safety issue: No ]
    will measure at month 30 (endpoint)and at weeks 0, 2, 4,6, 8, 10, 12, 16, 20, 24, and months 9, 12, 15, 18, 21, 24, 27 as well as the first and 4th week of each month in the drug holiday weight promotion arm

  • height [ Time Frame: month 18 ] [ Designated as safety issue: Yes ]
    in addition to the primary outcome of height at month 30, height will also be measured at month 6 as well as weeks 0, 2, 4,6, 8, 10, 12, 16, 20, 24 and months 9, 12, 15, 21, 24, 27. Subjects in the weight promotion arms will have their height measured monthly in addition to these times.

  • ADHD symptoms- teacher rated [ Time Frame: month 30 ] [ Designated as safety issue: No ]
    will measure at month 30 (endpoint)and at weeks 0, 2, 4,6, 8, 10, 12, 16, 20, 24, and months 9, 12, 15, 18, 21, 24, 27


Enrollment: 230
Study Start Date: November 2010
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: weight promotion treatment
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- either increased monitoring of growth, caloric supplement or drug holiday where only use ADHD medication for school
Drug: 12 hour methylphenidate product
medication to be taken daily for duration of study unless assigned to weight promotion arm
Other Names:
  • Concerta, OROS-MPH
  • CNS stimulants
Behavioral: increased monitoring of growth
monthly weight, height and BMI checks
Other Name: monitoring arm
Drug: drug holiday
switch from seven day a week dosing to medication only on school days
Other Name: Ritalin based product, CNS stimulants
Dietary Supplement: caloric supplement
continue current ADHD regimen and add one 8oz liquid caloric supplement at night
Other Name: nutripals
Active Comparator: behavior therapy
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: behavioral therapy
combination of individual and group parent training plus school consultation
Other Name: behavior modification
Experimental: ER stimulant
daily use of 12 hour extended release methylphenidate product
Drug: 12 hour methylphenidate product
medication to be taken daily for duration of study unless assigned to weight promotion arm
Other Names:
  • Concerta, OROS-MPH
  • CNS stimulants

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 3 for medication and month 6 for behavior therapy (because it can take longer for behavior therapy to work), 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

Ages Eligible for Study:   5 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 IQ 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01109849

Locations
United States, Florida
Center for Children and Families, Florida International University
Miami, Florida, United States, 33199
Sponsors and Collaborators
Florida International University
Investigators
Principal Investigator: James G Waxmonsky, MD Florida International University
  More Information

Additional Information:
No publications provided

Responsible Party: Florida International University
ClinicalTrials.gov Identifier: NCT01109849     History of Changes
Other Study ID Numbers: R01MH083692
Study First Received: April 21, 2010
Last Updated: April 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Florida International University:
ADHD
growth
BMI
stimulant medication

Additional relevant MeSH terms:
Methylphenidate
Central Nervous System Stimulants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors

ClinicalTrials.gov processed this record on September 29, 2014