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

ADHD Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01109849
• Other study ID #: R01MH083692
• Status: Completed
• Phase: Phase 4
• First received: April 21, 2010
• Last updated: August 10, 2016
• Start date: November 2010
• Est. completion date: April 2016

Study information

• Verified date: August 2016
• Source: Florida International University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 230
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 12 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• ADHD
• Growth

Intervention

Behavioral:
• behavioral therapy
combination of individual and group parent training plus school consultation

Drug:
• 12 hour methylphenidate product
medication to be taken daily for duration of study unless assigned to weight promotion arm

Behavioral:
• increased monitoring of growth
monthly weight, height and BMI checks

Drug:
• drug holiday
switch from seven day a week dosing to medication only on school days

Dietary Supplement:
• caloric supplement
continue current ADHD regimen and add one 8oz liquid caloric supplement at night

Locations

Country	Name	City	State
United States	Center for Children and Families, Florida International University	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Florida International University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	height	The primary endpoint will be height at month 30 which is study endpoint.	month 30	Yes
Secondary	weight	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.	month 30	Yes
Secondary	Body Mass Index (BMI)	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.	at month 30	Yes
Secondary	treatment adherence	will measure number of days medication and caloric supplement are taken as well as attendance at behavioral therapies	at month 30	Yes
Secondary	ADHD symptoms- parent rated	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	at month 30	No
Secondary	height	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.	month 18	Yes
Secondary	ADHD symptoms- teacher rated	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	month 30	No

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