Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Natural History of GACI With or Without ARHR2 or PXE

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03758534
Recruitment Status : Recruiting
First Posted : November 29, 2018
Last Update Posted : November 29, 2018
Sponsor:
Collaborator:
ICON plc
Information provided by (Responsible Party):
Frank Rutsch, Westfälische Wilhelms-Universität Münster

Brief 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.

Condition or disease Intervention/treatment
Generalized Arterial Calcification in Infancy Autosomal Recessive Hypophosphatemic Rickets Pseudoxanthoma Elasticum Other: No intervention

Detailed 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


Layout table for study information
Study Type : Observational
Estimated Enrollment : 80 participants
Observational Model: Cohort
Time Perspective: Retrospective
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)
Actual Study Start Date : March 15, 2018
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019



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


Primary Outcome Measures :
  1. Survival [ Time Frame: Recruitment for this study will end in March 2019 ]
    This study will record the survival rate in patients with GACI



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
Probands with proven history of generalized arterial calcification of infancy.
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03758534


Contacts
Layout table for location contacts
Contact: Frank Rutsch, MD +49251-8347700 frank.rutsch@ukmuenster.de
Contact: Kerstin Mueller, PhD +16042352172 kerstin.mueller@iconplc.com

Locations
Layout table for location information
Germany
WWU Munster Recruiting
Münster, Germany, 48149
Contact: Frank Rutsch, MD    +492518347700    frank.rutsch@ukmuenster.de   
Sponsors and Collaborators
Westfälische Wilhelms-Universität Münster
ICON plc
Investigators
Layout table for investigator information
Principal Investigator: Frank Rutsch, MD WWU Munster

Layout table for additonal information
Responsible Party: Frank Rutsch, Prof. Dr. Frank Rutsch, MD, Westfälische Wilhelms-Universität Münster
ClinicalTrials.gov Identifier: NCT03758534     History of Changes
Other Study ID Numbers: GACI Natural History
First Posted: November 29, 2018    Key Record Dates
Last Update Posted: November 29, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Calcinosis
Rickets
Rickets, Hypophosphatemic
Familial Hypophosphatemic Rickets
Pseudoxanthoma Elasticum
Arteriosclerosis
Vascular Calcification
Calcium Metabolism Disorders
Metabolic Diseases
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Vitamin D Deficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Hypophosphatemia
Phosphorus Metabolism Disorders
Hypophosphatemia, Familial
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders