Role of Nutrition and Hormones in Boys With Disordered Growth
Role of Nutrition and Hormones in Boys With Disordered Growth
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.
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.
-  INCLUSION CRITERIA

 Age 7-10 years, genital Tanner 1, significant short stature (current height less than
 2.25SD below the mean for age), body mass index (BMI) less than 25th percentile for age,
 weight-for-height less than 25th percentile, bone age less than 10 years and with delay
 greater than 1 year below chronological age, minimum of 6 months of documented height
 measurements performed in the pediatric endocrinology clinic using a stadiometer to permit
 accurate calculation of baseline growth velocity at time of enrollment, otherwise normal
 physical exam, expressed desire for medical intervention to promote growth, and assessment
 by a pediatric endocrinologist that the boy qualifies for GH treatment according to current
 FDA guidelines for the use of GH in children with idiopathic short stature (i.e., children
 who are determined not to have growth hormone deficiency but have height less than -2.25SD
 below the mean for age).

 EXCLUSION CRITERIA

 History of major/chronic illness, anosmia/hyposmia, any clinically significant
 abnormalities on biochemical testing. GH deficiency would be excluded prior to enrollment
 based on anthropometric and GH stimulation test data. Endocrinopathies (except stable
 thyroid replacement), skeletal dysplasias, participation in highly competitive endurance
 sports activities, diagnosis of ADHD with use of stimulant medication in the previous 3
 months will also be exclusion criteria.