Study to Examine Insulin Resistance During Growth Hormone Treatment for Short Stature Due to Low Birthweight
Recruitment status was: Recruiting
|Study Design:||Observational Model: Case-Crossover
Time Perspective: Prospective
|Official Title:||Growth Hormone and Insulin Resistance in Children With Intrauterine Growth Restriction|
|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)|
Drug: somatropin (rDNA)
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00120497
|Contact: Lynne L Levitsky, MDemail@example.com|
|Contact: David B Rhoads, PhDfirstname.lastname@example.org|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: David B Rhoads, PhD 617-724-2707 email@example.com|
|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|