Natural History of GACI With or Without ARHR2 or PXE

Pseudoxanthoma Elasticum Clinical Trial

Official title:

The Natural History of Generalized Arterial Calcification of Infancy (GACI) With or Without Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2) or Pseudoxanthoma Elasticum (PXE)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03758534
• Other study ID #: GACI Natural History
• Status: Recruiting
• Start date: March 15, 2018
• Est. completion date: December 31, 2019

Study information

• Verified date: November 2018
• Source: Westfälische Wilhelms-Universität Münster
• Contact: Frank Rutsch, MD
• Phone: +49251-8347700
• Email: frank.rutsch[@]ukmuenster.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Generalized arterial calcification of infancy (GACI) is an ultra-rare disorder with an estimated birth prevalence of around 1 in 400,000.1 GACI is generally fatal before birth or within the first six months after birth. The cause of death is frequently myocardial infarction or stroke. GACI is strongly associated with inactivating mutations in ectonucleotide pyrophosphate/ phosphodiesterase 1 (ENPP1). Many patients with GACI, including some without an ENPP1 mutation also present with mutations in adenosine triphosphate binding cassette transporter protein subfamily C member 6 (ABCC6). Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) and pseudoxanthoma elasticum (PXE) are believed to be closely related to GACI. ARHR2 is caused by mutations in the ENPP1 gene and PXE is caused by mutations in the ABCC6 gene, with both being observed among patients with GACI. The natural history of GACI and in particular its long term morbidity and mortality are poorly understood. The primary objective of this study is to characterize overall survival among patients with GACI, over time from birth.

Description:

Background:

Generalized arterial calcification of infancy (GACI) is an ultra-rare disorder with an estimated birth prevalence of around 1 in 400,000.1 GACI is characterized by extensive arterial calcifications, arterial stenosis, myointimal proliferation and periarticular calcifications. Individuals with GACI also experience calcification in other body areas, such as joints and organs. GACI is generally fatal before birth or within the first six months after birth. The cause of death is frequently myocardial infarction or stroke. GACI is strongly associated with inactivating mutations in ectonucleotide pyrophosphate/ phosphodiesterase 1 (ENPP1); around three quarters of GACI cases investigated had one or several ENPP1 mutations. Many patients with GACI, including some without an ENPP1 mutation also present with mutations in adenosine triphosphate binding cassette transporter protein subfamily C member 6 (ABCC6). Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) and pseudoxanthoma elasticum (PXE) are believed to be closely related to GACI. ARHR2 is caused by mutations in the ENPP1 gene5 and PXE is caused by mutations in the ABCC6 gene,3 with both being observed among patients with GACI. The natural history of GACI and in particular its long term morbidity and mortality are poorly understood, but a strong understanding of the condition will be crucial for further therapy development and drug testing. This study aims to address this knowledge gap.

Objectives:

The primary objective of this study is to characterize overall survival among patients with GACI, over time from birth.

Secondary objectives are to:

• Characterize the patient and disease characteristics;

• Describe symptomology at diagnosis and the change in symptomology over time;

• Describe treatment patterns specific to GACI or rickets

• Characterize mental/physical impairment, education, and employment situation;

• Characterize the sequelae of the disease;

• Prevalence of rickets; and

• Growth velocities.

Eligibility:

• GACI genotype (mutation in ENPP1 and/or ABCC6) confirmed through mutational analysis of the patient and a GACI phenotype confirmed by imaging or biopsy; or

• GACI phenotype confirmed with imaging, biopsy, or mutational analysis of the parents indicating a GACI genotype (mutation in ENPP1 and/or ABCC6) coinciding with symptoms of the patient.

Data will be collected for both living and deceased patients

Design:

Retrospective multicenter chart review

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2019
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• GACI genotype (mutation in ENPP1 and/or ABCC6) confirmed through mutational analysis of the patient and a GACI phenotype confirmed by imaging or biopsy; or

• GACI phenotype confirmed with imaging, biopsy, or mutational analysis of the parents indicating a GACI genotype (mutation in ENPP1 and/or ABCC6) coinciding with symptoms of the patient.

• Data will be collected for both living and deceased patients

Exclusion Criteria:

• Caregivers are not able to give written consent.

Related Conditions & MeSH terms

• Autosomal Recessive Hypophosphatemic Rickets
• Calcinosis
• Familial Hypophosphatemic Rickets
• Generalized Arterial Calcification in Infancy
• Pseudoxanthoma Elasticum
• Rickets
• Vascular Calcification

Intervention

Other:
• No intervention
This is a retrospective chart review study.

Locations

Country	Name	City	State
Germany	WWU Munster	Münster

Sponsors (2)

Lead Sponsor	Collaborator
Westfälische Wilhelms-Universität Münster	ICON plc

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival	This study will record the survival rate in patients with GACI	Recruitment for this study will end in March 2019