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Sponsors and Collaborators: |
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Genentech |
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Information provided by: | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
ClinicalTrials.gov Identifier: | NCT00149708 |
Growth hormone (GH) deficiency (GHD) in adulthood has been associated with changes in body composition (e.g. increased abdominal obesity, and reduced muscle mass), in organ functions (e.g. reduced cardiac systolic function), in metabolic parameters linked to increased risk of cardiovascular disease (e.g. increased serum total and LDL cholesterol, C reactive protein, and plasma fibrinogen), and with reduced bone density. These observations have been used to define the "adult GHD syndrome" and to advocate GH replacement therapy in GHD adults. However, most of the studies have been performed in patients who have had hypothalamic or pituitary diseases, and/or have undergone brain irradiation. Such patients are often chronically sick, and commonly lack other pituitary hormones, whose replacement therapies may not fully restore the physiological functions of the under-active glands. Reliable data on the existence of the AGHD syndrome and its response to GH therapy can be only obtained by studying patients that are otherwise healthy. However, isolated GH deficiency (IGHD) is a rare disease. In addition, up to 50% of patients who have been diagnosed with IGHD in childhood are no longer GH deficient as adults, making such study difficult to perform due to the scarcity of patients population. We have identified a very large homogeneous population of patients who have IGHD due to a homozygous mutation in the GHRH-receptor (GHRHR) gene that resides in a rural area of Brazil. None of the adult dwarf patients has ever been treated with hGH replacement. This population represents a unique model to study the effect of isolated lifetime lack of GH. We propose studies of physiological and metabolic parameters in subjects who are homozygous for this mutation and compare them with normal subjects residing in the same community.
The primary goal of this proposal is to determine the consequences of life-long lack of GH on body composition, muscle strength, cardiovascular status, cardiovascular risk factors, thyroid status and bone density and metabolism, and to test which of these parameters are reversed by a 6-month course of GH replacement therapy. In addition, we want to test the hypothesis that heterozygosity for this GHRHR mutation causes a phenotype that may be intermediate between the one present in homozygous normal subjects and in homozygous affected GHD patients. This is relevant because inactivating mutations in the GHRHR are being described with increasing frequency in populations of different genetic background, suggesting that individuals with faulty single GHRHR alleles may be present in significant numbers in the general population.
Condition | Intervention |
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Growth Hormone Deficiency |
Drug: growth hormone administration for 6 months |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Efficacy Study |
Official Title: | Consequence of Lifetime Isolated Growth Hormone Deficiency |
Estimated Enrollment: | 400 |
Study Start Date: | September 2005 |
Estimated Study Completion Date: | December 2008 |
Estimated Primary Completion Date: | December 2008 (Final data collection date for primary outcome measure) |
SPECIFIC AIM 1: To study anthropometric parameters, cardiovascular and metabolic status and cardiovascular risk profile, including inflammatory markers of cardiovascular relevance, muscle strength, bone density and bone metabolism, and thyroid status of twenty GH-naïve adult GHD subjects who are homozygous for a null GHRHR mutation and to compare them with twenty age- and sex- matched normal controls from the same population.
SPECIFIC AIM 2: To observe the changes in all the above parameters that occur in GHD subjects after a 6-months treatment with hGH replacement, and their reversibility after a 6-months washout period.
SPECIFIC AIM 3: To determine effect of heterozygosity for the GHRHR mutation. To this end, we propose to genotype a large number of apparently normal members of the Itabaianinha community with the goal of separating subjects homozygous for the wild-type allele from subjects heterozygous for the GHRHR mutation, and to compare their phenotype with the one observed in subjects homozygous for the wild type allele residing in the same geographical area.
Together, these studies will determine the effect of lifetime absence of GH on multiple organ functions and their response to hGH therapy, and will tell if heterozygosity for mutations in the GHRHR gene is associated with a detectable phenotype.
Ages Eligible for Study: | 18 Years to 80 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Roberto Salvatori, md | 410-955-3921 | salvator@jhmi.edu |
Brazil, Sergipe | |
Federal University of Sergipe | Recruiting |
Aracaju, Sergipe, Brazil, 49060 | |
Contact: Manuel H Aguiar-Oliveira, MD 79-3227-3026 herminio@infonet.com.br | |
Principal Investigator: Manuel H Aguiar-Oliveira, MD |
Principal Investigator: | Roberto Salvatori, MD | Johns Hopkins University |
Responsible Party: | Johns Hopkins University ( roberto salvatori, MD ) |
Study ID Numbers: | DK 65718 |
Study First Received: | September 6, 2005 |
Last Updated: | January 5, 2009 |
ClinicalTrials.gov Identifier: | NCT00149708 |
Health Authority: | United States: Federal Government |
Growth hormone Deficiency Cardiovascular risk Body composition |
Dwarfism Bone Diseases, Endocrine Hypopituitary dwarfism Hypothalamic Diseases Pituitary Diseases Endocrine System Diseases Central Nervous System Diseases Dwarfism, Pituitary |
Brain Diseases Bone Diseases Growth hormone deficiency Musculoskeletal Diseases Hypopituitarism Bone Diseases, Developmental Endocrinopathy |
Nervous System Diseases |