Evaluation of rhGH Replacement Therapy in Patients With Pseudohypoparathyroidism Type Ia (PHP Ia)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2007 by University of Milan.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by:
University of Milan
ClinicalTrials.gov Identifier:
NCT00497484
First received: July 5, 2007
Last updated: NA
Last verified: June 2007
History: No changes posted

July 5, 2007
July 5, 2007
Not Provided
Not Provided
growth velocity [ Time Frame: One year ]
Same as current
No Changes Posted
IGF-1 levels [ Time Frame: one month ]
Same as current
Not Provided
Not Provided
 
Evaluation of rhGH Replacement Therapy in Patients With Pseudohypoparathyroidism Type Ia (PHP Ia)
Evaluation of rhGH Replacement Therapy in Patients With Pseudohypoparathyroidism Type Ia (PHP Ia)

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.

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.

Interventional
Not Provided
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Pseudohypoparathyroidism
  • Growth Hormone Deficiency, Dwarfism
Drug: recombinant human somatotropin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
Not Provided
Not Provided
Not Provided

Inclusion Criteria:

  • Clinical and/or genetic diagnosis of Pseudohypoparathyroidism type Ia
  • Growth hormone deficiency

Exclusion Criteria:

  • Known malignancies
Both
1 Year to 18 Years
No
Contact information is only displayed when the study is recruiting subjects
Italy
 
NCT00497484
PHP-IA-rhGH
Not Provided
Not Provided
University of Milan
Eli Lilly and Company
Study Director: Paolo Beck-Peccoz, MD/PhD Endocrine Unit, Dpt. of Medical Sciences, Fondazione Policlinico IRCCS, Milan
University of Milan
June 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP