Clinical trial NCT01616095: Effects of Growth Hormone Supplementation to Adults With Growth Hormone Deficient on Metabolism and Adipose Tissue Molecular Phenotype
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Growth Hormone Deficiency
Keywords: Growth hormone deficiency
hrGH therapy
metabolic health
adipose tissue metabolism
adipose tissue inflammation
adipokines
Lead sponsor: Slovak Academy of Sciences
Sponsor class: OTHER_GOV
Collaborators: name: PFIZER, Bratislava, Slovakia
First posted: 2012-06-11
Enrollment: 44
Sex: ALL
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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).

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Effects of GH therapy to GHD adults - the whole body level
timeFrame: 12 months
measure: GH therapy effects on the endocrine, metabolic & inflammatory properties of adipose tissue
timeFrame: 2 years
Secondary outcomes:
measure: comparison of GHD & control population
timeFrame: 2 years
measure: Identification of the adiposity-associated parameters
timeFrame: 2 years
Other outcomes:
Locations:
city: Bratislava
country: Slovakia
facility: V th Internal Clinic, Univeristy Hospital Bratislava, Comenius University
city: Bratislava
country: Slovakia
facility: Inst. Exp. Endocrinology Slovak Acad Sci
city: Lubochna
country: Slovakia
facility: National Institute of Endocrinology and Diabetology
Study officials:
affiliation: Inst. Exp. Endocrinology SAS, Bratislava, Slovakia
name: Jozef Ukropec, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Inst. Exp. Endocrinology SAS, Bratislava, Slovakia
name: Barbara Ukropcova, MD, PhD
role: STUDY_CHAIR
affiliation: Inst. Exp. Endocrinology SAS, Bratislava, Slovakia
name: Iwar Klimes, prof, MD, PhD
role: STUDY_DIRECTOR
affiliation: Inst. Exp. Endocrinology SAS, Bratislava, Slovakia
name: Daniela Gasperikova, PhD
role: STUDY_CHAIR
affiliation: Dep. of Endocrinology, University Hospital, Comenius University, Bratislava
name: Juraj Payer, prof, MD, PhD
role: STUDY_CHAIR
affiliation: Dep. of Endocrinology, University Hospital, Comenius University, Bratislava
name: Martin Kuzma, MD
role: STUDY_CHAIR
affiliation: National Institute of Diabetology and Endocrinology, Lubochna, Slovakia
name: Mikulas Pura, MD, PhD
role: STUDY_CHAIR
affiliation: National Institute of Diabetology and Endocrinology, Lubochna, Slovakia
name: Peter Vanuga, MD, PhD
role: STUDY_CHAIR
affiliation: Inst Exp. Endocirnology SAS, Bratislava
name: Miroslav Vlcek, MD, PhD
role: STUDY_CHAIR
affiliation: Inst Exp. Endocirnology SAS, Bratislava
name: Adela Penesova, MD, PhD
role: STUDY_CHAIR
affiliation: Inst Exp. Endocirnology SAS, Bratislava
name: Miroslav Balaz, Mgr.
role: STUDY_CHAIR
affiliation: Inst Exp. Endocirnology SAS, Bratislava
name: Timea Kurdiova, Mgr.
role: STUDY_CHAIR
References:
citation: Ukropec J, Penesova A, Skopkova M, Pura M, Vlcek M, Radikova Z, Imrich R, Ukropcova B, Tajtakova M, Koska J, Zorad S, Belan V, Vanuga P, Payer J, Eckel J, Klimes I, Gasperikova D. Adipokine protein expression pattern in growth hormone deficiency predisposes to the increased fat cell size and the whole body metabolic derangements. J Clin Endocrinol Metab. 2008 Jun;93(6):2255-62. doi: 10.1210/jc.2007-2188. Epub 2008 Mar 11.