Ignite Creation Date:
2024-05-05 @ 6:31 PM
Last Modification Date:
2024-10-26 @ 9:34 AM
Study NCT ID:
NCT00497484
Status:
UNKNOWN
Last Update Posted:
2007-07-06
First Post:
2007-07-05
Brief Title:
Evaluation of rhGH Replacement Therapy in Patients With Pseudohypoparathyroidism Type Ia PHP Ia
Sponsor:
University of Milan
Organization:
University of Milan
Study Overview
Official Title:
Evaluation of rhGH Replacement Therapy in Patients With Pseudohypoparathyroidism Type Ia PHP Ia
Status:
UNKNOWN
Status Verified Date:
2007-06
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
We have recently demonstrated resistance to GHRH leading to GH deficiency in patients with Pseudohypoparathyroidism type 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
Detailed Description:
Albrights 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 Albrights 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
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 Albrights 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None