Skeletal Muscle Effects of GH in Boys

Recombinant Human Growth Hormone (GH): Effects on Metabolic Profile, Body Composition and Skeletal Muscle Strength and Function in Pre-pubertal Short Boys With and Without GH Deficiency

The purpose of the study is to measure the functional effects of recombinant GH in skeletal muscle, in addition to growth promotion, in short prepubertal boys with either growth hormone deficiency or idiopathic short stature. Patients will be similarly short. The investigators will also compare these values in the short stature cohort to those obtained in testing performed in normally growing age-matched healthy control boys not on GH. The group on GH will be studied before and after 6 and 12 months of GH treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: Growth Hormone Deficiency; Idiopathic Short Stature
• Intervention / Treatment: Drug: Somatropin injection

Detailed Description

Prepubertal boys with significant short stature (height SDS ≤-2.0) diagnosed with either GH deficiency or idiopathic short stature (ISS) who are identified as candidates for GH treatment will recruited. Subjects will have a battery of studies to assess skeletal muscle strength, agility, power and endurance, as well as assessment of body composition and energy expenditure before and after GH administration. GH (Somatropin) treatment at standard doses will be given as daily injections at bedtime. Subjects will be followed at three-month intervals per the clinical routine, when anthropometric measurements will be obtained. Baseline studies will be repeated at 6 and 12 months from initiation of treatment, each patient will serve as his own control pre and post GH.

A group of normally statured healthy boys will have the same testing as the study patients but without GH treatment to assess the impact of natural growth on the muscle measures above.

• Study Type: Observational
• Enrollment (Estimated): 45

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 11 years (Child)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Prepubertal boys with short stature defined as a height ≤-2 SDS with either GH deficiency (i.e., peak GH responses to pharmacologic stimuli <10ng/ml) or idiopathic short stature (i.e., normal GH, no identifiable pathology) will be studied.

Normally Statured Boys: A group of 15 healthy, normally statured (between 10th- 90th %), age-matched boys not on somatropin, preferably siblings (although not exclusively) will be studied similarly.

Description

Inclusion Criteria:

Short Stature Group

1. 30 boys between 6-11 years of age
2. Prepubertal
3. Short stature (height ≤ -2SDS) due to either GH deficiency or idiopathic
4. Stable treatment of other pituitary hormone deficiencies
5. Naïve to GH therapy, or GH discontinued at least 6 months prior to study

Normal Stature Group

1. 15 boys between 6-11 years of age
2. Prepubertal
3. Normal height (10th to 90th%)

Exclusion Criteria:

1. Actively growing brain tumors
2. Chronic medical conditions that could affect study outcomes
3. Long-term steroid use
4. Intense regular physical training programs or organized team sports

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Short Stature Boys; Prepubertal boys with short stature defined as a height ≤-2 SDS with either GH deficiency (defined as peak GH responses to pharmacologic stimuli <10ng/ml) or idiopathic short stature (i.e., no identifiable pathology) will be studied pre and post 12 months of GH therapy.	Drug: Somatropin injection; Boys with short stature will be studied for measures of: skeletal muscle strength, power, and endurance; muscle agility; lean body mass accrual; bone mineral density and resting energy expenditure before and after 6 months and 12 months of GH administration; Other Names: Norditropin; Recombinant Growth Hormone
Normally Statured Boys; A group of 15 healthy, normally statured (between 10th- 90th %), age-matched boys not on Growth Hormone replacement, preferably siblings (although not exclusively), will be recruited to serve as healthy controls.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skeletal muscle strength (Newtons)	Upper and lower body muscle strength will be assessed using a handheld dynamometer for manual muscle testing of peak force	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skeletal muscle power (Watts)	Lower extremity power will be assessed by vertical jump performed using a Power time mat	12 months
Muscle agility (seconds)	Muscle agility will be assessed by a timed shuttle run	12 months
Muscle endurance	Upper body muscular endurance will be assessed using a modified push up test for repetitions	12 months
Lean body mass accrual	Assessed by dual energy x-ray absorptiometry (DEXA) scan of the whole body	12 months
Bone mineral density	Assessed by DEXA scan of the lumbar spine and whole body	12 months
Resting energy expenditure	Indirect calorimetry will be performed after overnight fast	12 months

Collaborators and Investigators

• Sponsor: Nemours Children's Clinic
• Collaborators: Novo Nordisk A/S
• Investigators: Principal Investigator: Nelly Mauras, MD, Nemours Children's Clinic

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2019
• Primary Completion (Estimated): May 31, 2024
• Study Completion (Estimated): July 21, 2025

Study Registration Dates

• First Submitted: May 24, 2019
• First Submitted That Met QC Criteria: July 12, 2019
• First Posted (Actual): July 16, 2019

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: muscle strength; GH; short stature; prepubertal; boys; GH treatment; muscle agility
• Additional Relevant MeSH Terms: Endocrine System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Developmental; Dwarfism; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: #19-09; U111112218502 (Other Grant/Funding Number: Novo Nordisk)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No