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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01616095
Recruitment Status : Completed
First Posted : June 11, 2012
Last Update Posted : April 17, 2018
PFIZER, Bratislava, Slovakia
Information provided by (Responsible Party):
Jozef Ukropec, 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.

Condition or disease
Growth Hormone Deficiency

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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 : April 2011
Actual Primary Completion Date : May 2013
Actual Study Completion Date : August 2015

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

Primary Outcome Measures :
  1. Effects of GH therapy to GHD adults - the whole body level [ Time Frame: 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.

  2. GH therapy effects on the endocrine, metabolic & inflammatory properties of adipose tissue [ Time Frame: 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 :
  1. comparison of GHD & control population [ Time Frame: 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

  2. Identification of the adiposity-associated parameters [ Time Frame: 2 years ]
    to evaluate parameters associated primarily with adiposity which are largely independent on the severity of the GH deficiency

Biospecimen Retention:   Samples With DNA
plasma 2.5 ml, serum 5 ml, adipose tissue 300 mg taken by the percutaneous biopsy of abdominal subcutaneous adipose tissue, in local anaesthesia.

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Twenty growth hormone deficient adults, receiving supplementation with rhGH for 5 years (extensively examined in 2005-2006, prior to the start of rhGH therapy) and 20 age-, gender- and BMI- matched controls will enter the study. Both, GHD patients and controls will undergo an extensive clinical protocol, identical to that performed in 2005 (Ukropec et al., 2008a).

The possibility of drop-out of patients needs to be taken into consideration. Possible lowering of the numbers of participants due to drop-out of individuals tested in the Baseline Study will be resolved by either (i) using biological material obtained in the Baseline Study which was originally not subjected to an extensive molecular genetic testing due to the limited capacity and high cost of these analyses and/or by (ii) recruiting necessary amount of new patients with history of 5 years rhGH therapy (initial examination is missing).


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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01616095

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V th Internal Clinic, Univeristy Hospital Bratislava, Comenius University
Bratislava, Slovakia, 82606
Inst. Exp. Endocrinology Slovak Acad Sci
Bratislava, Slovakia, 83306
National Institute of Endocrinology and Diabetology
Lubochna, Slovakia, 03491
Sponsors and Collaborators
Slovak Academy of Sciences
PFIZER, Bratislava, Slovakia
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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

Additional Information:
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Responsible Party: Jozef Ukropec, PhD, Slovak Academy of Sciences Identifier: NCT01616095    
Other Study ID Numbers: GH GIIR - 2011
First Posted: June 11, 2012    Key Record Dates
Last Update Posted: April 17, 2018
Last Verified: April 2018
Keywords provided by Jozef Ukropec, Slovak Academy of Sciences:
Growth hormone deficiency
hrGH therapy
metabolic health
adipose tissue metabolism
adipose tissue inflammation
Additional relevant MeSH terms:
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Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs