Consequence of Lifetime Isolated Growth Hormone Deficiency

This study has been completed.
Sponsor:
Collaborator:
Genentech
Information provided by:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00149708
First received: September 6, 2005
Last updated: June 13, 2010
Last verified: June 2010
  Purpose

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
Growth Hormone Deficiency
Drug: growth hormone administration for 6 months

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Consequence of Lifetime Isolated Growth Hormone Deficiency

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • Body composition [ Time Frame: after 6 months of GH and after wash out (6 and 12 months) ] [ Designated as safety issue: No ]
  • Lipid levels [ Time Frame: after 6 months of GH and after 6 and 12 months of wash out ] [ Designated as safety issue: No ]
  • Heart function [ Time Frame: after 6 months of GH and after 6 and 12 months of wash out ] [ Designated as safety issue: No ]

Estimated Enrollment: 400
Study Start Date: September 2005
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: growth hormone administration for 6 months
    depot GH (Nutropin depot) 13.4 mg every 14 days
    Other Name: Nuropin depot
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Lifetime isolated and untreated growth hormone deficiency

Exclusion Criteria:

  • Age below 18 years, pregnancy, diabetes
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00149708

Locations
Brazil
Federal University of Sergipe
Aracaju, Sergipe, Brazil, 49060
Sponsors and Collaborators
Genentech
Investigators
Principal Investigator: Roberto Salvatori, MD Johns Hopkins University
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: roberto salvatori, MD, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00149708     History of Changes
Other Study ID Numbers: DK 65718 (completed)
Study First Received: September 6, 2005
Last Updated: June 13, 2010
Health Authority: United States: Federal Government

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Growth hormone
Deficiency
Cardiovascular risk
Body composition

Additional relevant MeSH terms:
Dwarfism, Pituitary
Endocrine System Diseases
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 August 19, 2014