Generalized Arterial Calcification in InfancyNCT03758534
Natural History of GACI With or Without ARHR2 or PXE
An observational study of Generalized Arterial Calcification in Infancy and Autosomal Recessive Hypophosphatemic Rickets, run by Universität Münster at 1 site in Germany.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Generalized Arterial Calcification in Infancy, Autosomal Recessive Hypophosphatemic Rickets, Pseudoxanthoma Elasticum
- How many people
- 80 participants
- Where
- 1 siteGermany
- Study dates
- 15 Mar 2018to 31 Dec 2019
- Phase
- Observational
- 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 Any age
- All sexes
- Child, Adult, Older adult
Study population: Probands with proven history of generalized arterial calcification of infancy.
Who may be able to join
- 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
Who cannot join
- Caregivers are not able to give written consent.
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
WWU Munster
Münster, 48149
Frank Rutsch, MD, +492518347700, frank.rutsch@ukmuenster.de
About this study
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)
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.
Read the 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
- Conditions
- Generalized Arterial Calcification in Infancy, Autosomal Recessive Hypophosphatemic Rickets, Pseudoxanthoma Elasticum
- Being tested
- No intervention
- Medical subject headings
- Arterial calcification of infancy, Hypophosphatemic Rickets, Autosomal Recessive, 1, Pseudoxanthoma Elasticum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionOther
This is a retrospective chart review study.
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival
This study will record the survival rate in patients with GACI
Measured: Recruitment for this study will end in March 2019
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2018
- Study start15 Mar 2018
- Primary completion31 Dec 2019 (estimated)
- Study completion31 Dec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Generalized Arterial Calcification in InfancyStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universität Münster
- Sponsor type
- University, hospital or other
- Collaborators
- ICON plc
- Responsible party
- Principal investigator, Frank Rutsch, Universität Münster
- Investigators
- Frank Rutsch, MD, Principal investigator, WWU Munster
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03758534
- Sponsor's protocol ID
- GACI Natural History
- Status last verified
- Nov 2018
- First submitted
- 28 Nov 2018
- Last updated
- 29 Nov 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03758534
- Acronym / sponsor ID
- GACI Natural History
- Conditions
- Generalized Arterial Calcification in Infancy, Autosomal Recessive Hypophosphatemic Rickets, Pseudoxanthoma Elasticum
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Universität MünsterUniversity, hospital or other
- Collaborators
- ICON plc
- Study start
- 15 Mar 2018 (actual)
- Primary completion
- 31 Dec 2019 (estimated)
- Study completion
- 31 Dec 2019 (estimated)
- First posted
- 29 Nov 2018 (actual)
- 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.
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.
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
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Sex
- All
- Age groups
- Child, Adult, Older adult
- Study population
- Probands with proven history of generalized arterial calcification of infancy.
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (1 listed)
- Caregivers are not able to give written consent.
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 |
|---|---|---|
| No interventionThis is a retrospective chart review study. | Other | – |
Primary outcome
Survival
Time frame: Recruitment for this study will end in March 2019
This study will record the survival rate in patients with GACI
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2018.
- Individual participant dataSharing planned: No
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.
Frank Rutsch, MD principal investigator
WWU Munster
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Generalized Arterial Calcification in Infancy and Autosomal Recessive Hypophosphatemic Rickets, run by Universität Münster at 1 site in Germany.
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 3 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 29 Nov 2018. 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 Germany. 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?
Contact Frank Rutsch, MD (+49251-8347700, frank.rutsch@ukmuenster.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival (time frame: Recruitment for this study will end in March 2019). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Nov 2018.