Effects of Growth Hormone Supplementation to Adults With Growth Hormone Deficient on Metabolism and Adipose Tissue Molecular Phenotype

Completed

• Conditions: Growth Hormone Deficiency

• Registration Number: NCT01616095
• Lead Sponsor: Slovak Academy of Sciences

Brief Summary

This study is designed as a follow up study to that performed in 2005.

In the Baseline study (2005) extensive clinical whole body metabolic phenotyping was combined with in depth molecular and cellular biology analyses aimed at investigating the adipose tissue morphology as well as metabolic and inflammatory phenotypes in the adult GHD patients. Results published in (Ukropec et al., 2008)

In this study identical endpoints will be investigated with the same methodology and within the same population; in order to seek relevant answers to questions on how the 6-yrs of rhGH therapy affects the

* whole body insulin sensitivity

* energy expenditure

* body fat distribution

* hepatic and skeletal muscle lipid content;

as well as how it influences the adipose tissue

* endocrine,

* metabolic \&

* inflammatory phenotypes.

The strength of the planned study lies in the extensive whole body and adipose tissue phenotyping before and after the 6-year rhGH replacement therapy, that allows to determine the long-term effects of rhGH replacement therapy in GHD adults.

Envisaged weakness is the limited size of the population; GHD adults (n=20); controls \[age BMI and gender matched\] (n=20). This, however, reflects \[is limited by\] the complexity of the study protocol as well as the stringency of the inclusion criteria.

The clinical data obtained by methods of - integrated physiology would provide an excellent interpretation background for molecular-genetic studies at the tissue (adipose tissue) and cellular (adipocytes) level. Integration of the two could bring a new quality in the investigators understanding of metabolic derangements present in GHD, and will allow extending the investigators knowledge on the mechanisms of the long-term rhGH-therapy-induced improvement on body composition, metabolic health and the cardiovascular risk.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-04
• Study First Submitted: 2012-06-07
• Study First Submitted QC: 2012-06-08
• Study First Posted: 2012-06-11
• Primary Completion: 2013-05
• Study Completion: 2015-08
• Status Verified: 2018-04
• Last Update Submitted: 2018-04-14
• Last Update Posted: 2018-04-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

We will follow inclusion-exclusion criteria which are very much like those used in the pilot study performed in 2005.

• Briefly, duration of the GHD prior to entering the study should last for at least 3 years prior rhGH treatment starts. Age of individuals eligible to enter should be 20-50 years old. All patients and healthy control volunteers will provide the witnessed written informed consent before entry into the study.
• It has to be noted that differences in the etiology of GHD might influence several of the outcomes we plan to measure. Presence or absence of possible bias should therefore be excluded for each specific outcome prior further statistical data analysis. Individuals with different degree of pituitary deficiency will therefore be eligible to enter the study.
• Complex information on the adequacy of the hormone replacement therapy will be based on the serum levels of growth hormone, insulin-like growth factor 1, free thyroid hormone, testosterone/estradiol, urinary free cortisol FT4, and morning cortisol. Examination and laboratory testing relevant to this study will be performed within 6 months of entering the study. The 24-hour urinary free cortisol will only be determined in individuals hospitalized in a period of two month prior to the study entry.

Exclusion Criteria

• None of the patients should receive lipid lowering treatment. Patients with malignant disease, diabetes mellitus, existing vascular disease and uncontrolled hypertension are not eligible to enter this study.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
GH therapy effects on the endocrine, metabolic & inflammatory properties of adipose tissue	2 years	to investigate the effects of long-term (5 years) growth hormone supplementation on the subcutaneous adipose tissue (i) endocrine, (ii) metabolic and (iii) inflammatory phenotype in adult GHD patients, by extensive profiling of adipose tissue protein \& gene expression (protein antibody arrays \& real-time PCR) which could identify potential molecular mechanisms associated with abdominal obesity and insulin resistance modulated by rhGH replacement therapy.
Effects of GH therapy to GHD adults - the whole body level	12 months	to determine the effects of a long-term (6 years) growth hormone supplementation on the whole-body metabolic phenotype in adult GHD patients (namely (i) insulin sensitivity, (ii) energy expenditure, (iii) body fat distribution and (iv) bone mineral density, (v) glucose tolerance, (vi) hepatic and skeletal muscle lipid content as well as (vii) serum lipids and (viii) inflammatory markers in circulation.

Secondary Outcome Measures

Name	Time	Method
Identification of the adiposity-associated parameters	2 years	to evaluate parameters associated primarily with adiposity which are largely independent on the severity of the GH deficiency
comparison of GHD & control population	2 years	to compare the whole-body metabolic profile and subcutaneous adipose tissue phenotype of rhGH supplemented GHD adults with that of the healthy control group

Trial Locations

Locations (3)

V th Internal Clinic, Univeristy Hospital Bratislava, Comenius University; 🇸🇰 Bratislava, Slovakia

Inst. Exp. Endocrinology Slovak Acad Sci; 🇸🇰 Bratislava, Slovakia

National Institute of Endocrinology and Diabetology; 🇸🇰 Lubochna, Slovakia