Role of Nutrition and Hormones in Boys With Disordered Growth
Condition: Short Stature; Constitutional Delay of Growth and Development; Dwarfism, Pituitary
MeSH terms: Dwarfism; Dwarfism, Pituitary
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will determine whether adding more calories to the diet helps boys with growth
      problems grow better while being treated with Nutropin, a growth hormone that is used to help
      children grow taller. The Food and Drug Administration has approved Nutropin for use in
      children who are very short. This study will examine whether giving nutritional supplements
      in addition to Nutropin can help children grow better than with Nutropin alone.

      Boys between 7 and 10 years of age who are very short and below average in weight, but are
      otherwise healthy may be eligible for this study. Candidates must qualify for Nutropin
      treatments to boost their growth. Boys will be recruited for the study from the Nemours
      Children's Clinic in Jacksonville, FL, and from the National Institutes of Health in
      Bethesda, MD.

      Participants are randomly assigned to one of two treatment groups. One group is observed for
      6 months and then receives a Nutropin injection every day for 12 months. The second group
      drinks 8 ounces of a high-calorie beverage called Pediasure every day for 6 months and then
      receives Nutropin plus Pediasure every day for 12 months. In addition to treatment,
      participants undergo the following tests and procedures at the schedule indicated: Baseline,
      3, 6, 9, 12, 15 and 18 months

        -  Clinical examination

        -  Height measurement

        -  Body composition assessment: Skin-fold thickness calipers are used in four places on the
           body to estimate body fat

        -  Bioelectric impedance: A small amount of electrical current is used to calculate the
           percentage of body fat.

      Baseline, 6, 12, and 18 months

        -  Blood tests

        -  Bone age x-ray: x-ray of the left hand to measure growth potential

        -  DEXA (dual energy x-ray absorptiometry) scan: x-ray scan to measure body fat, muscle,
           and bone mineral content. The subject lies on a flat table during the scan.

      Baseline, 6, and 12 months

        -  Record of dietary intake: Parents are asked to write down everything the child eats and
           drinks for 3 days. Using this record, a dietitian calculates the daily caloric intake.

        -  Total energy expenditure: This test determines how much energy the child uses. For the
           test, the child drinks water labeled with harmless isotopes (heavy oxygen and heavy
           hydrogen). For the next 10 days he collects urine in plastic tubes at home. At the end
           of the 10 days, the parents bring the urine to the clinic for analysis to determine how
           fast the labeled water leaves the body. This information is used to calculate how much
           energy the child expends each day.

      Participants' weight is measured at 2 and 4 weeks, and then monthly for the remainder of the
      18-month study.
    

Detailed description: 
      We propose a pilot study to examine the role of nutrition and its interaction with growth
      hormone (GH) therapy in boys with very short stature who also have delayed bone age
      characteristic of constitutional delay of growth and maturation (CDGM). Recent studies have
      suggested that insufficient caloric intake may contribute to the pathophysiology of CDGM.
      This prompted us to consider whether nutritional intervention may benefit children with
      severe short stature who also have CDGM.

      To investigate this further, we would like to enroll a total of 20 boys (10-15 boys in
      Jacksonville, Florida and 5-10 boys at the NIH, Bethesda, Maryland), ages 7-10 years, who are
      otherwise healthy, but have significant short stature (height SDS less than -2.25 = the
      current FDA approved indication for the use of GH in idiopathic short stature), delayed bone
      age (greater than 12 months below chronologic age), and low BMI and weight-for-height (less
      than 25th percentile). Ten boys will be randomized to receive observation for 6 months,
      followed by GH therapy for 12 months. Ten boys will be randomized to receive daily liquid
      nutritional supplementation for 6 months, followed by combined GH therapy and nutritional
      supplementation for 12 months. For all subjects, weight gain will be monitored at 2 weeks, 4
      weeks, and then monthly. Height gain and body composition (using skin-fold thickness calipers
      and bioelectric impedance analysis) will be assessed every 3 months. Total energy
      expenditure, three-day dietary history, bone age, body composition/bone mineral density
      (using dual energy X-ray absorptiometry), and laboratory studies (IGF1, IGFBP3, pre-albumin,
      transferrin, ghrelin, fasting insulin, glucose, and lipid profile) will be obtained at
      baseline and then every 6 months.

      We hypothesize that nutritional supplementation alone can lead to small improvements in
      linear growth and lean body mass accrual, but when combined with GH therapy, can augment the
      anabolic actions of GH, thereby resulting in even greater improvements in linear growth
      velocity and lean body mass accrual than GH alone. If the data from this study confirm this
      trend, we would then like to proceed with a larger study, appropriately powered based on the
      results of this pilot.
    

Intervention name(s): Growth Hormone Therapy
Intervention type(s): Drug
Intervention MeSH terms: Hormones
Primary purpose: Treatment
Keywords: Short Stature; Constitutional Delay of Growth and Development; Body Composition; Energy Expenditure; Dietary Supplements; Constitutional Delay of Growth; CDGM