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

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Terminated

CT.gov ID

NCT00121875

Collaborator

(none)

Enrollment

Location

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Turner Syndrome Idiopathic Short Stature	Drug: somatropin (rDNA)

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.

Study Design

Study Type:

Observational

Actual Enrollment :

1 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Growth Hormone and Insulin Resistance in Girls With Turner Syndrome or Idiopathic Short Stature

Study Start Date :

Jun 1, 2005

Actual Study Completion Date :

Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: recombinant human growth hormone, Nutropin-AQ

Arm

Intervention/Treatment

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 Names:

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 Names:

recombinant human growth hormone, Nutropin-AQ

Outcome Measures

Primary Outcome Measures

to compare the effect of GH on IMCL content in the two subject groups (Turner syndrome vs. ISS) [3 months]

Secondary Outcome Measures

to assess the relationship of IMCL to IR-associated plasma markers in each groups [3 months]
to assess the relationship of IMCL to the effect of GH therapy in each groups [3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

7 Years to 14 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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