Study to Examine Insulin Resistance During Growth Hormone Treatment for Short Stature Due to Low Birthweight

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2011 by Massachusetts General Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00120497
First received: July 13, 2005
Last updated: July 19, 2011
Last verified: July 2011
  Purpose

Insulin resistance is common among children with low birthweight. Moreover, growth hormone treatment for ensuing short stature also causes insulin resistance. Our objective is to examine these processes. Insulin resistance has recently been linked to the accumulation of stores of fat in muscle cells which can be measured by MRI. We hypothesize that children who are short due to low birthweight have increased muscle fat stores, but that growth hormone treatment will paradoxically reverse this association. To test this hypothesis, muscle fat stores will be measured in children who are short due to low birthweight before and after receiving growth hormone therapy. Other parameters linked to insulin resistance (glucose tolerance, blood markers, and body composition) will also be assessed. This study may lead to ways to increase growth hormone safety and dose limitations.


Condition Intervention Phase
Fetal Growth Retardation
Drug: somatropin (rDNA)
Phase 4

Study Type: Observational
Study Design: Observational Model: Case-Crossover
Time Perspective: Prospective
Official Title: Growth Hormone and Insulin Resistance in Children With Intrauterine Growth Restriction

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Biospecimen Retention:   Samples Without DNA

Blood


Estimated Enrollment: 12
Study Start Date: July 2005
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: somatropin (rDNA)

    Dosage form/strength: 13.8 mg powder in 2-chamber cartridge; reconstitutes to 10 mg/ml

    Dosage regimen: 0.48 mg/kg/week

    Route/rate of administration: subcutaneous injection, daily dose

    Other Names:
    • Genotropin
    • recombinant human growth hormone
Detailed Description:

Growth hormone (GH) is an effective height-enhancing treatment for short stature. One underlying disorder is intrauterine growth restriction (IUGR). Increased growth enhances quality of life as well as improving body composition, metabolism, and lipid distribution. However, both GH therapy and IUGR can cause insulin resistance. Scientists have recently linked insulin resistance to the accumulation of fat inside muscle cells (intramyocellular lipids or IMCL). Although GH generally reduces overall body fat, its effect on IMCL has not yet been examined. This association can be examined in children with IUGR initiating GH treatment for short stature.

Hypothesis: Children with IUGR will have increased IMCL linked to insulin resistance, but GH treatment may paradoxically reverse this association.

Objectives: To assess changes in IMCL during GH therapy and to increase our knowledge of GH action.

Study design: Prepubertal children initiating a course of GH therapy indicated by persistent short stature as a result of IUGR will be recruited to participate in a crossover study.

  • IMCL (soleus and tibialis anterior) will be measured non-invasively by proton magnetic resonance spectroscopy (1H-MRS)
  • Body composition will be measured by DEXA and morphometry
  • Whole body insulin sensitivity (IS) will be assessed by oral glucose tolerance
  • Levels of plasma lipids and hormones will be measured

Endpoints: The primary endpoint will be to define the effect of GH on IMCL content in IUGR children. Secondary endpoints will be (i) to compare the relationships between IMCL and IS before and after GH therapy, and (ii) to identify the correlative changes in plasma hormones and metabolites that may underlie the IMCL changes.

Significance: IMCL is anticipated to be a valuable probe for understanding GH effects on glucose homeostasis. This study is intended to reveal strategies for enhancing GH efficacy without compromising IS. New pharmacological approaches to manage GH-induced glucose intolerance would be important in counteracting this limiting factor in GH dosing.

  Eligibility

Ages Eligible for Study:   8 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Children, age 6-12 years old, with short stature associated with low birth weight

Criteria

Inclusion Criteria:

  • height < 5%-ile
  • birthweight < 10%-ile for gestational age
  • gestation: ≥ 36 weeks
  • male or female
  • age: 8-12 years
  • BMI = 10-90%-ile
  • normal childhood activity, no physical or other limitations
  • bone age ≤ 12 years
  • normal, balanced diet (20-40% calories from fat)

Exclusion Criteria:

  • puberty (beyond Tanner Stage 1)
  • diabetes in subject or first degree relative
  • sex steroid therapy
  • chronic conditions requiring medication
  • other causes of short stature (e.g., Prader-Willi, intracranial lesions, hypopituitarism, Turner syndrome, GHD, etc.)
  • significant systemic disease (pulmonary, cardiac, renal, or other)
  • non-removable metal
  • other conditions judged by the investigator to pose a hazard (including history of neoplasm)
  • simultaneous participation in another medical investigation or trial
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00120497

Contacts
Contact: Lynne L Levitsky, MD 617-726-2909 llevitsky@partners.org
Contact: David B Rhoads, PhD 617-724-2707 rhoads@helix.mgh.harvard.edu

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: David B Rhoads, PhD    617-724-2707    rhoads@helix.mgh.harvard.edu   
Sub-Investigator: Martin Torriani, MD         
Sub-Investigator: Bijoy J Thomas, MBBS         
Sub-Investigator: Miriam Bredella, M.D.         
Sub-Investigator: Paul A Boepple, M.D.         
Sub-Investigator: David B Rhoads, Ph.D.         
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Lynne L Levitsky, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Lynne L. Levitsky, M.D., Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00120497     History of Changes
Other Study ID Numbers: 2005P-000384, IRG 2004-0964
Study First Received: July 13, 2005
Last Updated: July 19, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
short stature
intrauterine growth restriction
insulin resistance
intramyocellular lipid
small for gestational age
glucose tolerance

Additional relevant MeSH terms:
Fetal Growth Retardation
Insulin Resistance
Fetal Diseases
Pregnancy Complications
Growth Disorders
Pathologic Processes
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Hormones
Insulin
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Hypoglycemic Agents

ClinicalTrials.gov processed this record on April 15, 2014