Consequence of Lifetime Isolated Growth Hormone Deficiency

Growth Hormone Deficiency Clinical Trial

Official title:

Consequence of Lifetime Isolated Growth Hormone Deficiency

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00149708
• Other study ID #: DK 65718 (completed)
• Status: Completed
• Phase: N/A
• First received: September 6, 2005
• Last updated: June 13, 2010
• Start date: September 2005
• Est. completion date: December 2009

Study information

• Verified date: June 2010
• Source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 400
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Lifetime isolated and untreated growth hormone deficiency

Exclusion Criteria:

• Age below 18 years, pregnancy, diabetes

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dwarfism, Pituitary
• Endocrine System Diseases
• Growth Hormone Deficiency

Intervention

Drug:
• growth hormone administration for 6 months
depot GH (Nutropin depot) 13.4 mg every 14 days

Locations

Country	Name	City	State
Brazil	Federal University of Sergipe	Aracaju	Sergipe

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Genentech, Inc.

Country where clinical trial is conducted

Brazil, 

References & Publications (1)

Alcântara MR, Salvatori R, Alcântara PR, Nóbrega LM, Campos VS, Oliveira EC, Oliveira MH, Souza AH, Aguiar-Oliveira MH. Thyroid morphology and function in adults with untreated isolated growth hormone deficiency. J Clin Endocrinol Metab. 2006 Mar;91(3):86 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Body composition		after 6 months of GH and after wash out (6 and 12 months)	No
Primary	Lipid levels		after 6 months of GH and after 6 and 12 months of wash out	No
Primary	Heart function		after 6 months of GH and after 6 and 12 months of wash out	No