- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00497484
Evaluation of rhGH Replacement Therapy in Patients With Pseudohypoparathyroidism Type Ia (PHP Ia)
Study Overview
Status
Intervention / Treatment
Detailed Description
Albright's Hereditary Osteodystrophy is a rare autosomal dominant disease characterized by a constellation of physical features including short stature, central obesity, round face, brachydactyly, subcutaneous calcifications and mental retardation. In the same family, it may present associated to end organ resistance to the action of different hormones, primarily PTH, TSH and gonadotropins and in this case it is named PHP type Ia, or on the contrary we may find it as an isolated defect and this is the case of PPHP.
In about 80% of affected families, heterozygous loss of function mutations in the Gs alpha gene are detected. It is of interest mutations inherited from the mother always lead to the complete form of the disorder, that is PHP; on the contrary when the same mutations are inherited from the father, patients show the physical abnormalities of Albright's Osteodystrophy, without any evidence of hormone resistance. This pattern of inheritance is consistent with a tissue-specific paternal imprinting of the Gs alpha gene. Imprinting is an epigenetic phenomenon by which one of the 2 alleles undergoes partial or total loss of expression; in the case of the Gs alpha gene one would expect that only the paternal allele should be lost in specific endocrine tissues, such as the kidney, the thyroid and the gonad, which are the target organs resistant to hormone action in PHP Ia. Indeed, our group demonstrated that in specific human endocrine tissues also Gs alpha transcription mainly derives from the maternal allele (Mantovani et al., J Clin Endocrinol Metab, 2002. 87: 4736-4740). In particular a predominant maternal origin of transcription was found in thyroid and gonad and these data are consistent with the clinical finding of TSH and gonadotropin resistance present in patients affected with PHP. Interestingly, we observed a predominance of the maternal allele also in the pituitary gland, an organ which is not classically included among the target organs resistant to hormone action in PHP Ia.
Following this observation, we have recently demonstrated resistance to GHRH leading to GH deficiency in most of our patients with PHP Ia (Mantovani et al., J Clin Endocrinol Metab, 2003. 88: 4070-4074). The purpose of this study is to evaluate the effect of at least 1-year GH replacement in these patients. In particular, we will focus our attention on growth velocity in children affected with this disease.
Study Type
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
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Milan, Italy, 20122
- Endocrine Unit, Dpt. of Medical Sciences, Fondazione Policlinico IRCCS
-
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Clinical and/or genetic diagnosis of Pseudohypoparathyroidism type Ia
- Growth hormone deficiency
Exclusion Criteria:
- Known malignancies
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
growth velocity
Time Frame: One year
|
One year
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
IGF-1 levels
Time Frame: one month
|
one month
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Paolo Beck-Peccoz, MD/PhD, Endocrine Unit, Dpt. of Medical Sciences, Fondazione Policlinico IRCCS, Milan
Publications and helpful links
General Publications
- Mantovani G, Maghnie M, Weber G, De Menis E, Brunelli V, Cappa M, Loli P, Beck-Peccoz P, Spada A. Growth hormone-releasing hormone resistance in pseudohypoparathyroidism type ia: new evidence for imprinting of the Gs alpha gene. J Clin Endocrinol Metab. 2003 Sep;88(9):4070-4. doi: 10.1210/jc.2002-022028.
- Germain-Lee EL, Groman J, Crane JL, Jan de Beur SM, Levine MA. Growth hormone deficiency in pseudohypoparathyroidism type 1a: another manifestation of multihormone resistance. J Clin Endocrinol Metab. 2003 Sep;88(9):4059-69. doi: 10.1210/jc.2003-030028.
- Mantovani G, Ferrante E, Giavoli C, Linglart A, Cappa M, Cisternino M, Maghnie M, Ghizzoni L, de Sanctis L, Lania AG, Beck-Peccoz P, Spada A. Recombinant human GH replacement therapy in children with pseudohypoparathyroidism type Ia: first study on the effect on growth. J Clin Endocrinol Metab. 2010 Nov;95(11):5011-7. doi: 10.1210/jc.2010-1649. Epub 2010 Aug 18.
Study record dates
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Endocrine System Diseases
- Genetic Diseases, Inborn
- Musculoskeletal Diseases
- Bone Diseases
- Metabolism, Inborn Errors
- Bone Diseases, Metabolic
- Calcium Metabolism Disorders
- Bone Diseases, Developmental
- Metal Metabolism, Inborn Errors
- Dwarfism
- Pseudohypoparathyroidism
- Pseudopseudohypoparathyroidism
Other Study ID Numbers
- PHP-IA-rhGH
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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