Genetic Study of Families Affected by Paget's Disease of Bone - Full Text View

Sponsors and Collaborators:	Assistance Publique - Hôpitaux de Paris Novartis Association Rhumatisme et Travail
Information provided by:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00747994

Purpose

Paget's disease of bone is a frequent bone disorder which usually starts after the age of 40 and which is characterized by bone pain and deformities. Although often without any symptoms, this disease may have severe complications such as fissures, fractures, neurological compression, or deafness. In some cases, it is a genetic disorder transmitted with a dominant autosomal pattern of inheritance: one of the two parents carrying the disease transmits it to his offspring with a risk of 50% for each child. Since 2002, the first gene involved in Paget's disease of bone is known and 14 mutations of this gene have been published. A study confirmed that the presence of those mutations was associated with younger age of onset and more extensive disease. Thus, the knowledge of those genetic factors in the relatives of an affected individual allows the screening of the patients with a higher risk for complications, who may benefit from a medical follow up and earlier treatment, in order to avoid complications. Indeed, Paget's disease of bone may be treated efficiently by bisphosphonates.

This project aims at identifying and collecting over one year, 15 affected individuals affected by Paget's disease of bone and the relatives up to the second degree of relativeness (a total of 100 individuals is expected). The blood samples may be analysed in order to search for mutations of the previously known gene and/or to search for new mutations on new genes.

Condition
Paget's Disease of Bone

MedlinePlus related topics: Bone Diseases Paget's Disease of Bone

U.S. FDA Resources

Study Type:	Observational
Study Design:	Family-Based, Retrospective
Official Title:	Genetic Study of Families Affected by Paget's Disease of Bone

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:

To identify new mutations or new haplotypes of mutations already identified, and/or to identify new mutations in new genes of Paget's disease of bone. [ Time Frame: 2007-2008 ] [ Designated as safety issue: No ]

Biospecimen Retention: Samples With DNA

Biospecimen Description:

collection of extracted DNA, RNA and serum samples and urinary samples

Estimated Enrollment:	100
Study Start Date:	September 2007
Estimated Study Completion Date:	September 2008

Groups/Cohorts
1

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

15 patients affected by Paget's disease of bone and their relatives at the first or second degree of relativeness total of about 100 individuals

Criteria

Inclusion Criteria:

Patient aged over 18 years,
patient who underwent a clinical examination,
patient who gave its written consent,
1. Each individual (index case) affected by Paget's disease of bone (with diagnosis confirmed by alkalies phosphatases analysis and/or imaging with bone scintigraphy and radiographies on the affected sites with a typical aspect of the disease), and :
  - At least one relative affected by Paget's disease of bone with confirmed diagnosis (see above),
  - Or an age at diagnosis < 55 years,
  - Or a polyostotic involvement with at least 4 affected bones,
  - Or the presence of a bone deformity at the time of the diagnosis.
2. Each relative with established phenotype by imaging (bone scintigraphy and/or radiographies), at first or second degree of relativeness of an index case defined in (a).

Exclusion Criteria:

Index case with not confirmed Paget's disease of bone by biological and/or radiological examinations,
Index with confirmed Paget's disease but without relative with the same disease, with an age at diagnosis >55 years, with a number of affected bones <4, without any bone deformity at the time of the diagnosis
Healthy relatives of a Paget patient who refuse to undergo bone scintigraphy and bone radiographies.
Individuals < 18 years
Pregnant or breast
feeding woman-individual living ina sanitary or social establishment
individual under guardianship
individual in an emergency situation
individual unable to give his consent
incarcerated individual
patient not covered by healthcare institutions

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00747994

Contacts

Contact: Laetitia Michou, MD, PhD

+33 149956291

laetitia.michou@lrb.aphp.fr

Locations

France, Ile de France
CHU Lariboisière	Recruiting
Paris, Ile de France, France, 75010
Contact: Laetitia Michou, MD PhD +33 1 49 95 62 91 laetitia.michou@lrb.aphp.fr
Principal Investigator: Laetitia Michou, MD PhD

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Novartis

Association Rhumatisme et Travail

Investigators

Study Director:

Laetitia Michou, MD PhD

CHU Lariboisière

More Information

Publications:

Collet C, Michou L, Audran M, Chasseigneaux S, Hilliquin P, Bardin T, Lemaire I, Cornélis F, Launay JM, Orcel P, Laplanche JL. Paget's disease of bone in the French population: novel SQSTM1 mutations, functional analysis, and genotype-phenotype correlations. J Bone Miner Res. 2007 Feb;22(2):310-7.

Morissette J, Laurin N, Brown JP. Sequestosome 1: mutation frequencies, haplotypes, and phenotypes in familial Paget's disease of bone. J Bone Miner Res. 2006 Dec;21 Suppl 2:P38-44.

Responsible Party:	Department Clinical Research ( Yannick Vacher )
Study ID Numbers:	P070203
Study First Received:	September 5, 2008
Last Updated:	September 5, 2008
ClinicalTrials.gov Identifier:	NCT00747994
Health Authority:	France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Paget's disease of bone
Relatives
Mutations screening
Haplotypes analysis

Linkage analysis
< 55 years
4 > or = Waffected Bones
bone deformity

Study placed in the following topic categories:

Musculoskeletal Diseases
Osteitis Deformans
Congenital Abnormalities

Osteitis
Bone Diseases
Pagets disease

ClinicalTrials.gov processed this record on January 14, 2009