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

Pseudohypoparathyroidism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00497484
• Other study ID #: PHP-IA-rhGH
• Status: Active, not recruiting
• Phase: N/A
• First received: July 5, 2007
• Last updated: July 5, 2007

Study information

• Verified date: June 2007
• Source: University of Milan
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 18 Years

Eligibility

Inclusion Criteria:

• Clinical and/or genetic diagnosis of Pseudohypoparathyroidism type Ia

• Growth hormone deficiency

Exclusion Criteria:

• Known malignancies

Study Design

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

Related Conditions & MeSH terms

• Dwarfism, Pituitary
• Growth Hormone Deficiency, Dwarfism
• Pseudohypoparathyroidism

Intervention

Drug:
• recombinant human somatotropin

Locations

Country	Name	City	State
Italy	Endocrine Unit, Dpt. of Medical Sciences, Fondazione Policlinico IRCCS	Milan

Sponsors (2)

Lead Sponsor	Collaborator
University of Milan	Eli Lilly and Company

Country where clinical trial is conducted

Italy, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	growth velocity		One year
Secondary	IGF-1 levels		one month