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

NCT01616095 | Completed DMC

• 1 other identifier: GH GIIR - 2011
• Study Type: observational
• Target: 44
• Locations: 1 country
• Sites: 3

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.

Conditions

Growth Hormone Deficiency

Keywords

Growth hormone deficiency; hrGH therapy; metabolic health; adipose tissue metabolism; adipose tissue inflammation; adipokines

Outcome Measures

Primary Outcomes (2)

• Effects of GH therapy to GHD adults - the whole body level

  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.

  12 months

• GH therapy effects on the endocrine, metabolic & inflammatory properties of adipose tissue

  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.

  2 years

Secondary Outcomes (2)

• comparison of GHD & control population

  2 years

• Identification of the adiposity-associated parameters

  2 years

Study Arms (2)

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

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Slovak Academy of Sciences: lead
• PFIZER, Bratislava, Slovakia: collaborator

Study Sites (3)

V th Internal Clinic, Univeristy Hospital Bratislava, Comenius University

Bratislava, 82606, Slovakia

Location

Inst. Exp. Endocrinology Slovak Acad Sci

Bratislava, 83306, Slovakia

Location

National Institute of Endocrinology and Diabetology

Ľubochňa, 03491, Slovakia

Location

Related Publications (1)

• 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.

  PMID: 18334583 BACKGROUND

Related Links

• link to the website of the Institute of Experimental Endocrinology Slovak Academy of Sciences

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.

MeSH Terms

Conditions

Dwarfism, Pituitary

Condition Hierarchy (Ancestors)

Dwarfism; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Bone Diseases, Endocrine; Hypopituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Study Officials

• Jozef Ukropec, PhD

  Inst. Exp. Endocrinology SAS, Bratislava, Slovakia

  PRINCIPAL INVESTIGATOR

• Barbara Ukropcova, MD, PhD

  Inst. Exp. Endocrinology SAS, Bratislava, Slovakia

  STUDY CHAIR

• Iwar Klimes, prof, MD, PhD

  Inst. Exp. Endocrinology SAS, Bratislava, Slovakia

  STUDY DIRECTOR

• 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

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: June 7, 2012
• First Posted: June 11, 2012
• Study Start: April 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: August 1, 2015
• Last Updated: April 17, 2018

Record last verified: 2018-04

Locations

SL (3)