PseudohypoparathyroidismNCT00497484
Evaluation of rhGH Replacement Therapy in Patients With Pseudohypoparathyroidism Type Ia (PHP Ia)
A study testing recombinant human somatotropin in people with Pseudohypoparathyroidism and Growth Hormone Deficiency, Dwarfism, run by University of Milan at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Pseudohypoparathyroidism, Growth Hormone Deficiency, Dwarfism
- What is being tested?
- recombinant human somatotropin
- How many people
- Not given
- Where
- 1 siteItaly
- Study dates
- Start not givento not given
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Clinical and/or genetic diagnosis of Pseudohypoparathyroidism type Ia
- Growth hormone deficiency
Who cannot join
- Known malignancies
Trial locations and contacts
1 site in 1 country.
Italy1 site
Endocrine Unit, Dpt. of Medical Sciences, Fondazione Policlinico IRCCS
Milan, 20122
About this study
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.
Read the 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.
- Being tested
- recombinant human somatotropin
- Medical subject headings
- Pseudohypoparathyroidism, Dwarfism, Pituitary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
recombinant human somatotropinDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
growth velocity
Measured: One year
Secondary outcomes (1)
IGF-1 levels
Measured: one month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2007 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for PseudohypoparathyroidismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Sponsor and investigators
- Lead sponsor
- University of Milan
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Investigators
- Paolo Beck-Peccoz, MD/PhD, Study director, Endocrine Unit, Dpt. of Medical Sciences, Fondazione Policlinico IRCCS, Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00497484
- Sponsor's protocol ID
- PHP-IA-rhGH
- Status last verified
- Jun 2007
- First submitted
- 5 Jul 2007
- Last updated
- 6 Jul 2007
- Results posted
- No
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.
PubMed 12970263Germain-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.
PubMed 12970262Mantovani 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.
PubMed 20719837
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of rhGH Replacement Therapy in Patients With Pseudohypoparathyroidism Type Ia (PHP Ia)
- ClinicalTrials.gov ID
- NCT00497484
- Acronym / sponsor ID
- PHP-IA-rhGH
- Study type
- Interventional
- Recruitment status
- Unknown status
- Lead sponsor
- University of MilanUniversity, hospital or other
- Collaborators
- Eli Lilly and Company
- First posted
- 6 Jul 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Clinical and/or genetic diagnosis of Pseudohypoparathyroidism type Ia
- Growth hormone deficiency
Key exclusion criteria (1 listed)
- Known malignancies
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| recombinant human somatotropin | Drug | – |
Primary outcome
growth velocity
Time frame: One year
1 secondary outcome
IGF-1 levels
Time frame: one month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2007.
- Background: PubMed 12970263Mantovani 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.
- Background: PubMed 12970262Germain-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.
- Derived from this study: PubMed 20719837Mantovani 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paolo Beck-Peccoz, MD/PhD study director
Endocrine Unit, Dpt. of Medical Sciences, Fondazione Policlinico IRCCS, Milan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing recombinant human somatotropin in people with Pseudohypoparathyroidism and Growth Hormone Deficiency, Dwarfism, run by University of Milan at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Jul 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
growth velocity (time frame: One year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00497484, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2007.