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Study of People With Generalized Arterial Calcification of Infancy (GACI) or Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2)

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ClinicalTrials.gov Identifier: NCT03478839
Recruitment Status : Recruiting
First Posted : March 27, 2018
Last Update Posted : August 15, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )

Brief Summary:

Background:

Generalized Arterial Calcification of Infancy (GACI) is a very rare disorder. It can be fatal before birth or by age 6 months. Anumber of people with GACI survive into adulthood. Those adults suffer from side effects of the disease, including rickets. It is unknown how common the disease Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2) is. It also has side effects. GACI and ARHR2 are usually caused by the mutations in the same gene. There are no approved treatments for the two diseases. Researchers want to study people with these diseases and their family members. This may help understand these rare and unique diseases better. The data could lead to new treatments for GACI and ARHR2.

Objectives:

To better understand the progression of GACI and ARHR2 and how genes might play a role in them.

Eligibility:

People with GACI or ARHR2, both living and deceased, and their parents and siblings.

Design:

Participants will allow researchers to access their medical records. They will give this consent by mail, email, or fax.

Data will be taken from the records. Participants names will not be used. Instead, they will be identified by a code.

Participants may give a blood sample.

If a participant withdraws from the study, their data and samples will be destroyed. However, the coded clinical data in the official medical record and data in databases will NOT be destroyed.


Condition or disease
Generalized Arterial Calcification of Infancy Autosomal Recessive Hypophosphatemic Rickets Type 2

Detailed Description:

This is a retrospective, natural history study of patients with Generalized Arterial Calcification of Infancy (GACI) or Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2). GACI is an ultra-rare disorder with an estimated birth prevalence of around 1 in 200,000.1 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 parenchymal 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, and hypertension and congestive heart failure are common in fetuses and infants with GACI. The first six months of life are considered a critical period for GACI patients, and approximately 85% of infants with GACI do not survive beyond this period (Moran 1975). However, the mortality rate decreases substantially among patients who do survive beyond the critical period. Reports exist of patients with GACI who survived into adulthood, but the frequency of this occurrence is unknown, and adult patients suffer from a number of sequelae such as cognitive impairment related to stroke. ARHR2 is characterized by short stature, dental caries, and bone deformities, and biochemically by hypophosphatemia, hyperphosphaturia and elevated plasma alkaline phosphatase. The disease frequency is unknown.

GACI and ARHR2 are most commonly due to mutations of ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1), or less often from mutations in ABCC6 (adenosine triphosphate binding cassette transporter protein subfamily C member 6). No founder mutations are known, and thus no ethnic predilection is known. Both the GACI and ARHR2 phenotypes are potentially fatal or associated with severe morbidity, with no FDA-approved drugs or proven treatments. Animal data suggest that enzyme replacement therapy with ENPP1-Fc may be effective in preventing morbidity or mortality of GACI and ARHR2.

PXE (pseudoxanthoma elasticum) is an autosomal recessive disorder due to mutations in ABCC6 or, less often, ENPP1. PXE is characterized by ectopic calcification of the skin, eyes, cardiovascular system and gastrointestinal system. This study will not focus on PXE but will collect data on PXE patients, particularly when their presentation suggests elements of the GACI or ARHR2 phenotypes.

The main objective of this study is to collect historical control data for future comparison to data from patients treated with ENPP1-Fc so we can develop ENPP1-Fc as a treatment for GACI or ARHR2. In addition, this study will allow for a better understanding of the disease course to design future treatment trials. The study will utilize data obtained predominantly from chart review. The goal is to enroll 100 participants, which include both living and deceased individuals with GACI or ARHR2, and/or their parents and siblings. Our study will be jointly and collaboratively conducted by the NIH and Inozyme.


Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Study of People With Generalized Arterial Calcification of Infancy (GACI) or Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2)
Actual Study Start Date : April 17, 2018
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020


Group/Cohort
1
People with GACI or ARHR2, both living and deceased, and their parents and siblings.



Primary Outcome Measures :
  1. CRF completion [ Time Frame: ongoing ]


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 100 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
patients treated with GACI
Criteria
  • INCLUSION & EXCLUSION CRITERIA:

Based upon study purpose, participants enrolled in this protocol must:

  1. Have genetic confirmation of one of the following:

    1. GACI due to ENPP1 or ABCC6 mutations
    2. ARHR2 due to ENPP1 mutations
    3. PXE due to ABCC6 or ENPP1 mutations
  2. Carry the clinical diagnosis of GACI, ARHR2 or PXE
  3. Consent or, if applicable, assent to participate in the study
  4. Have sufficient chart information to allow for the completion of at least one of the protocol s objectives.

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): NCT03478839


Contacts
Contact: Carlos R Ferreira, M.D. (240) 393-5441 ferreiracr@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Human Genome Research Institute (NHGRI)
Investigators
Principal Investigator: Carlos R Ferreira, M.D. National Human Genome Research Institute (NHGRI)

Additional Information:
Publications:
Responsible Party: National Human Genome Research Institute (NHGRI)
ClinicalTrials.gov Identifier: NCT03478839     History of Changes
Other Study ID Numbers: 180064
18-HG-0064
First Posted: March 27, 2018    Key Record Dates
Last Update Posted: August 15, 2018
Last Verified: August 7, 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) ):
Generalized Arterial Calcification of Infancy
Autosomal Recessive Hypophosphatemic Rickets
Pseudoxanthoma Elasticum
Idiopathic Infantile Arterial Calcification

Additional relevant MeSH terms:
Calcinosis
Rickets
Rickets, Hypophosphatemic
Familial Hypophosphatemic Rickets
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