Study to Identify Markers of Insulin Resistance During Growth Hormone Treatment for Short Stature

This study has been terminated.
(Enrollment was too low.)
Sponsor:
Information provided by:
Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00121875
First received: July 14, 2005
Last updated: September 28, 2009
Last verified: September 2009
  Purpose

Growth hormone treatment improves body fat distribution but also causes insulin resistance. Scientists have recently linked insulin resistance with special stores of fat in the muscles, which can be measured by magnetic resonance imaging (MRI). The researchers hypothesize that growth hormone will paradoxically reverse the linkage between muscle fat stores and insulin resistance. To assess this association and to investigate the cause(s), the researchers will measure muscle fat stores during growth hormone treatment. Other parameters linked to insulin resistance (glucose tolerance, blood markers, and body composition) will also be assessed. This study may lead to improved strategies for monitoring growth hormone therapy.


Condition Intervention Phase
Turner Syndrome
Idiopathic Short Stature
Drug: somatropin (rDNA)
Phase 4

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Growth Hormone and Insulin Resistance in Girls With Turner Syndrome or Idiopathic Short Stature

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • to compare the effect of GH on IMCL content in the two subject groups (Turner syndrome vs. ISS) [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • to assess the relationship of IMCL to IR-associated plasma markers in each groups [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • to assess the relationship of IMCL to the effect of GH therapy in each groups [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

Blood


Enrollment: 1
Study Start Date: June 2005
Study Completion Date: December 2008
Groups/Cohorts Assigned Interventions
Turner syndrome
Girls, aged 7-14, with short stature due to Turner syndrome and eligible for growth hormone therapy
Drug: somatropin (rDNA)

Form/Strength: 10 mg aqueous suspension; 5 mg/ml

Dosage/Frequency: 0.35 mg/kg/week, daily divided doses

Duration: 6 months with 3-month washout period

Other Name: recombinant human growth hormone, Nutropin-AQ
Control / idiopathic short stature
Girls, aged 7-14, with idiopathic short stature and eligible for growth hormone therapy
Drug: somatropin (rDNA)

Form/Strength: 10 mg aqueous suspension; 5 mg/ml

Dosage/Frequency: 0.35 mg/kg/week, daily divided doses

Duration: 6 months with 3-month washout period

Other Name: recombinant human growth hormone, Nutropin-AQ

Detailed Description:

Growth hormone (GH) treatment can cause insulin resistance (IR) despite its overall favorable influence on body fat composition. IR is associated with special stores of fat in the muscle (intramyocellular lipid or IMCL), which can be measured by MRI. The researchers hypothesize that changes in IR during GH treatment will be associated with a predictable, but possibly contradictory, change in muscle fat stores. Girls receiving GH for short stature, due to Turner syndrome or idiopathic short stature (ISS), will be studied both during and without GH treatment to assess the impact of GH treatment on muscle fat stores.

Hypothesis: Girls with Turner syndrome will have increased IMCL, corresponding to their insulin resistance, when compared to girls with ISS. GH treatment may paradoxically reverse this association in girls with Turner syndrome.

Objectives: The objectives are to assess changes in IMCL during GH therapy and to increase the researchers' knowledge of GH action.

Study Design: Prepubertal girls receiving GH therapy for short stature due to Turner syndrome or ISS will be recruited to participate in a crossover study. Subjects will be studied twice: first during GH treatment and at baseline, following washout without GH for 3 months. GH treatment for up to 6 months will be provided for eligible girls not currently receiving GH. Assessments include:

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

Endpoints: The primary endpoint is to define the effect of GH on IMCL content in girls with Turner syndrome versus girls with ISS. The secondary endpoint is to examine how GH affects IMCL content by identifying correlative changes in plasma hormones and metabolites.

Significance: This study is intended to find improved strategies for monitoring GH therapy. In addition, IMCL is anticipated to be a valuable probe for understanding GH effects on glucose homeostasis.

  Eligibility

Ages Eligible for Study:   7 Years to 14 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Girls, age 7-14 years, with short stature due to Turner syndrome or with idiopathic short stature

Criteria

Inclusion Criteria:

  • Girls, with Turner syndrome or ISS; height standard deviation score (SDS) ≤ -2
  • Bone age ≤ 12 years
  • Normal birthweight
  • Body mass index (BMI) = 10th-90th percentile
  • Normal childhood activity; no physical or other limitations
  • 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 (treatment for hypothyroidism is permissible)
  • Significant systemic disease (pulmonary, cardiac, renal, or other)
  • Non-removable metal
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00121875

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
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: NCT00121875     History of Changes
Other Study ID Numbers: 2004P-002800, L3452n
Study First Received: July 14, 2005
Last Updated: September 28, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
short stature
insulin resistance
body composition
Turner syndrome
intramyocellular lipid
glucose tolerance

Additional relevant MeSH terms:
Dwarfism
Insulin Resistance
Turner Syndrome
Gonadal Dysgenesis
Primary Ovarian Insufficiency
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Genetic Diseases, Inborn
Endocrine System Diseases
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Disorders of Sex Development
Urogenital Abnormalities
Sex Chromosome Disorders of Sex Development
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities
Sex Chromosome Disorders
Chromosome Disorders
Gonadal Disorders
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Hormones
Insulin
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on July 28, 2014