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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
PFIZER, Bratislava, Slovakia
Information provided by (Responsible Party):
Jozef Ukropec, Slovak Academy of Sciences
ClinicalTrials.gov Identifier:
NCT01616095
First received: June 7, 2012
Last updated: July 18, 2013
Last verified: July 2013
  Purpose

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
Growth Hormone Deficiency

Study Type: Observational
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Slovak Academy of Sciences:

Primary Outcome Measures:
  • Effects of GH therapy to GHD adults - the whole body level [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 44
Study Start Date: June 2011
Estimated Study Completion Date: August 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

Ages Eligible for Study:   21 Years to 50 Years
Genders Eligible for Study:   Both
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).

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01616095

Locations
Slovakia
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
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
  More Information

Additional Information:
Publications:
Responsible Party: Jozef Ukropec, PhD, Slovak Academy of Sciences
ClinicalTrials.gov Identifier: NCT01616095     History of Changes
Other Study ID Numbers: GH GIIR - 2011
Study First Received: June 7, 2012
Last Updated: July 18, 2013
Health Authority: Slovakia: State Institute for Drug Control

Keywords provided by Slovak Academy of Sciences:
Growth hormone deficiency
hrGH therapy
metabolic health
adipose tissue metabolism
adipose tissue inflammation
adipokines

Additional relevant MeSH terms:
Endocrine System Diseases
Dwarfism, Pituitary
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
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014