- ICH GCP
- Rejestr badań klinicznych w USA
- Badanie kliniczne NCT00149708
Consequence of Lifetime Isolated Growth Hormone Deficiency
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.
Przegląd badań
Status
Warunki
Interwencja / Leczenie
Szczegółowy opis
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.
Typ studiów
Zapisy (Oczekiwany)
Faza
- Nie dotyczy
Kontakty i lokalizacje
Lokalizacje studiów
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Sergipe
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Aracaju, Sergipe, Brazylia, 49060
- Federal University of Sergipe
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Kryteria uczestnictwa
Kryteria kwalifikacji
Wiek uprawniający do nauki
Akceptuje zdrowych ochotników
Płeć kwalifikująca się do nauki
Opis
Inclusion Criteria:
- Lifetime isolated and untreated growth hormone deficiency
Exclusion Criteria:
- Age below 18 years, pregnancy, diabetes
Plan studiów
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Leczenie
- Przydział: Nielosowe
- Model interwencyjny: Zadanie dla jednej grupy
- Maskowanie: Brak (otwarta etykieta)
Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Ramy czasowe |
---|---|
Body composition
Ramy czasowe: after 6 months of GH and after wash out (6 and 12 months)
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after 6 months of GH and after wash out (6 and 12 months)
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Lipid levels
Ramy czasowe: after 6 months of GH and after 6 and 12 months of wash out
|
after 6 months of GH and after 6 and 12 months of wash out
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Heart function
Ramy czasowe: after 6 months of GH and after 6 and 12 months of wash out
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after 6 months of GH and after 6 and 12 months of wash out
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Współpracownicy i badacze
Współpracownicy
Śledczy
- Główny śledczy: Roberto Salvatori, MD, Johns Hopkins University
Publikacje i pomocne linki
Publikacje ogólne
- Alcantara MR, Salvatori R, Alcantara PR, Nobrega 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):860-4. doi: 10.1210/jc.2005-2555. Epub 2006 Jan 4.
- Araujo VP, Aguiar-Oliveira MH, Oliveira JL, Rocha HM, Oliveira CR, Rodrigues TM, Nunes MA, Britto IM, Ximenes R, Barreto-Filho JA, Meneguz-Moreno RA, Pereira RM, Valenca EH, Oliveira-Neto LA, Vicente TA, Blackford A, Salvatori R. Arrest of atherosclerosis progression after interruption of GH replacement in adults with congenital isolated GH deficiency. Eur J Endocrinol. 2012 Jun;166(6):977-82. doi: 10.1530/EJE-12-0062. Epub 2012 Mar 13.
- Barbosa JA, Salvatori R, Oliveira CR, Pereira RM, Farias CT, Britto AV, Farias NT, Blackford A, Aguiar-Oliveira MH. Quality of life in congenital, untreated, lifetime isolated growth hormone deficiency. Psychoneuroendocrinology. 2009 Jul;34(6):894-900. doi: 10.1016/j.psyneuen.2009.01.001. Epub 2009 Jan 31.
- Menezes Oliveira JL, Marques-Santos C, Barreto-Filho JA, Ximenes Filho R, de Oliveira Britto AV, Oliveira Souza AH, Prado CM, Pereira Oliveira CR, Pereira RM, Ribeiro Vicente Tde A, Farias CT, Aguiar-Oliveira MH, Salvatori R. Lack of evidence of premature atherosclerosis in untreated severe isolated growth hormone (GH) deficiency due to a GH-releasing hormone receptor mutation. J Clin Endocrinol Metab. 2006 Jun;91(6):2093-9. doi: 10.1210/jc.2005-2571. Epub 2006 Mar 7.
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów
Zakończenie podstawowe (Rzeczywisty)
Ukończenie studiów (Rzeczywisty)
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Oszacować)
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Oszacować)
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Słowa kluczowe
Dodatkowe istotne warunki MeSH
- Choroby mózgu
- Choroby ośrodkowego układu nerwowego
- Choroby Układu Nerwowego
- Choroby układu mięśniowo-szkieletowego
- Choroby podwzgórza
- Choroby kości
- Choroby kości, endokrynologiczne
- Choroby przysadki
- Karłowatość
- Choroby kości, rozwojowe
- Niedoczynność przysadki
- Karłowatość, przysadka mózgowa
- Choroby układu hormonalnego
- Fizjologiczne skutki leków
- Hormony, substytuty hormonów i antagoniści hormonów
- Hormony
Inne numery identyfikacyjne badania
- DK 65718 (completed)
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