Study to Examine Insulin Resistance During Growth Hormone Treatment for Short Stature Due to Low Birthweight
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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 |
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) |
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Drug: somatropin (rDNA)
- Genotropin
- recombinant human growth hormone
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
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.
Ages Eligible for Study: | 8 Years to 12 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Sampling Method: | Non-Probability Sample |
Children, age 6-12 years old, with short stature associated with low birth weight
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
Contact: Lynne L Levitsky, MD | 617-726-2909 | llevitsky@partners.org |
Contact: David B Rhoads, PhD | 617-724-2707 | rhoads@helix.mgh.harvard.edu |
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. |
Principal Investigator: | Lynne L Levitsky, MD | Massachusetts General Hospital |
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 October 16, 2012