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

Sponsor

Slovak Academy of Sciences (Other)

Overall Status

Completed

CT.gov ID

NCT01616095

Collaborator

PFIZER, Bratislava, Slovakia (Other)

Enrollment

Locations

Actual Duration (Months)

14.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Growth Hormone Deficiency

Study Design

Study Type:

Observational

Actual Enrollment :

44 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

The Effect of a Long-Term Growth Hormone Supplementation on the Whole-Body Metabolic Characteristics and Adipose Tissue Phenotype in Growth Hormone Deficient Adults: the 5-yr Follow-up

Actual Study Start Date :

Apr 1, 2011

Actual Primary Completion Date :

May 1, 2013

Actual Study Completion Date :

Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Adults with Growth Hormone Deficiency if multiple hormonal deficiences exist, long term adequate supplementation is provided and tightly monitored.
Healthy Controls matched for BMI, age, and gender

Outcome Measures

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	V th Internal Clinic, Univeristy Hospital Bratislava, Comenius University	Bratislava	Slovakia	82606
2	Inst. Exp. Endocrinology Slovak Acad Sci	Bratislava	Slovakia	83306
3	National Institute of Endocrinology and Diabetology	Lubochna	Slovakia	03491

Sponsors and Collaborators

Slovak Academy of Sciences
PFIZER, Bratislava, Slovakia

Investigators

Principal Investigator: Jozef Ukropec, PhD, Inst. Exp. Endocrinology SAS, Bratislava, Slovakia
Study Chair: Barbara Ukropcova, MD, PhD, Inst. Exp. Endocrinology SAS, Bratislava, Slovakia
Study Director: Iwar Klimes, prof, MD, PhD, Inst. Exp. Endocrinology SAS, Bratislava, Slovakia
Study Chair: Daniela Gasperikova, PhD, Inst. Exp. Endocrinology SAS, Bratislava, Slovakia
Study Chair: Juraj Payer, prof, MD, PhD, Dep. of Endocrinology, University Hospital, Comenius University, Bratislava
Study Chair: Martin Kuzma, MD, Dep. of Endocrinology, University Hospital, Comenius University, Bratislava
Study Chair: Mikulas Pura, MD, PhD, National Institute of Diabetology and Endocrinology, Lubochna, Slovakia
Study Chair: Peter Vanuga, MD, PhD, National Institute of Diabetology and Endocrinology, Lubochna, Slovakia
Study Chair: Miroslav Vlcek, MD, PhD, Inst Exp. Endocirnology SAS, Bratislava
Study Chair: Adela Penesova, MD, PhD, Inst Exp. Endocirnology SAS, Bratislava
Study Chair: Miroslav Balaz, Mgr., Inst Exp. Endocirnology SAS, Bratislava
Study Chair: Timea Kurdiova, Mgr., Inst Exp. Endocirnology SAS, Bratislava