Searching for the cause of unexplained high levels of calcium in infants: The Canadian and European experience
| ISRCTN | ISRCTN88115690 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN88115690 |
| Secondary identifying numbers | CIHR ERA-13293 |
- Submission date
- 06/12/2015
- Registration date
- 13/01/2016
- Last edited
- 14/01/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Genetic Diseases
Plain English summary of protocol
Background and study aims
Calcium is one of the most important minerals in the body. As well as building strong bones and teeth, it plays an important role in helping blood to clot, nerves to send messages and muscles to contract. Idiopathic infantile hypercalcemia (IIH) is a rare disorder in young children (typically aged 3-7 months) in which very high levels of calcium are present in the blood (hypercalcemia) and urine (hypercalciuria). Too much calcium can lead to a number of problems, such as weakened bones (as the calcium in the blood is often taken from the bones, stomach problems (such as nausea and vomiting), and even heart and brain problems. One of the most common features of IIH is problems with the kidneys, such as kidney stones (build-up of calcium deposits in the kidneys) or kidney failure, as the kidneys have to work harder than usual to get rid of excess calcium, The usual treatment for IIH is to temporarily reduce calcium or vitamin D (a vitamin required for the body to absorb calcium) intake. In most cases, the cause of IIH is unknown however previous study showed that 30% of infants suffering from IIH in Europe have a change (mutation) in a protein (CYP24A1) that breaks down vitamin D (CYP24A1). When this mutation in CYP24A1 occurs, normal vitamin D breakdown is interrupted causing vitamin D levels to build up and too much calcium to be absorbed in the intestine. Another study has shown that some people, who experience hypercalcemia as adults, also have this mutation. The aim of this study is to investigate how common the CYP24A1 mutation is in infants suffering from IIH and their families, across Europe and North America.
Who can participate?
Children who have suffered from hypercalcemia and hypercalciuria, without a known cause, with their biological parents and siblings.
What does the study involve?
The families come to the Children’s Hospital where they give consent to take part in the study. The child and other available family members (parents and siblings) all have a blood test in order to test blood calcium levels, DNA (genetic material) and vitamin D levels. A urine sample is also collected which is tested for calcium. The family history for each participant is then reviewed to see how many relatives have had calcium problems or kidney stones. Children taking part also have a bone density test (to test bone strength), which involves a type of x-ray procedure while the child is lying down.
What are the possible benefits and risks of participating?
Participants could benefit from gaining knowledge about whether they are carriers of the CYP24A1 mutation. They can then ensure that they do not consume too much calcium and reduce the likelihood of developing kidney stones. There are no significant risks of taking part however participants may experience discomfort, bruising and pain during blood tests.
Where is the study run from?
Six children’s hospitals in Canada.
When is the study starting and how long is it expected to run for?
September 2013 to December 2016
Who is funding the study?
Canadian Institutes of Health Research (Canada)
Who is the main contact?
Dr Celia Rodd
Contact information
Scientific
Children's Hospital of Winnipeg
FW 302 685 William Ave
Winnipeg
R3E 0Z2
Canada
Study information
| Study design | Multi-centre cross sectional observational study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cross sectional study |
| Study setting(s) | Hospital |
| Study type | Screening |
| Scientific title | Idiopathic Infantile Hypercalcemia: European-Canadian Consortium |
| Study acronym | IIH |
| Study objectives | Mutations in CYP24A1 lead to aberrant control of vitamin D hormone levels in blood and tissues and impaired mineral ion homeostasis, leading to soft-tissue calcification as a result of long-term hypercalcemia. |
| Ethics approval(s) | 1. University of Manitoba Research Ethics Board, 15/04/2015, ref: DBMS-033-14 IIH-ECC 2. University of Calgary, 12/02/2013, ref: REB13-0216 3. Montreal Children's Hospital Research Ethics Board, 06/06/2011, ref: 11-163 4. The Research Ethics Board of the University of Laval, 18/02/2015, ref: 2015-2240 |
| Health condition(s) or problem(s) studied | Idiopathic infantile hypercalcemia |
| Intervention | Children with hypercalcemia and hypercalciuria or isolated hypercalciuria without an identified aetiology will be approached to try to determine if they have mutations in CYP24A. Most children will have a single sample of blood taken for vitamin D metabolomics and DNA mutational analyses. If the family consents, we may consider examining a few other novel genes involved in hypercalcemia such as sodium phosphate transporters NaPiIIa and -Iic. The blood will be stored for a maximum of 7 years and then discarded as per protocol. For some young infants, we may consider obtaining several samples while hypercalcemic to see if there is a difference in the vitamin D metabolite profile. The samples will be stored the same amount of time (7 years). |
| Intervention type | Other |
| Primary outcome measure | Number of children with presumed IIH that have CYP24A1 mutations is determined using DNA mutational analyses at the end of the study period. |
| Secondary outcome measures | Utility of vitamin D metabolite ratios to diagnose and manage children with known CYP24A1 mutations is determined using LC-MS/MS (tandem mass spectrometry) at the end of the study period. |
| Overall study start date | 01/01/2013 |
| Completion date | 31/12/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Sex | Both |
| Target number of participants | n=200 for all sites |
| Total final enrolment | 41 |
| Key inclusion criteria | Children inclusion criteria: 1. Documented hypercalcemia on at least 2 occasions without any known etiology 2. Idiopathic hypercalciuria without any known etiology Family members inclusion criteria: None |
| Key exclusion criteria | Children exclusion criteria: Children with known causes of hypercalcemia or hypercalciuria Family members inclusion criteria: None |
| Date of first enrolment | 01/01/2013 |
| Date of final enrolment | 31/12/2016 |
Locations
Countries of recruitment
- Canada
Study participating centres
Montreal
Quebec
H4A 3J1
Canada
Winnipeg
R3A 1R8
Canada
Calgary
T3B 6A8
Canada
Québec
G1V 4G2
Canada
Halifax
B3K 6R8
Canada
Ottawa
K1H 8L1
Canada
Sponsor information
Government
60 Elgin Street, 9th Floor
Address Locator 4809A
Ottawa ON K1A 0W9
Canada
Ottawa
K1A 0W9
Canada
| Phone | +1 613 954 1968 |
|---|---|
| info@cihr-irsc.gc.ca | |
"ROR" |
https://ror.org/01gavpb45 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- Instituts de Recherche en Santé du Canada, Canadian Institutes of Health Research (CIHR), CIHR_IRSC, Canadian Institutes of Health Research | Ottawa ON, CIHR, IRSC
- Location
- Canada
Results and Publications
| Intention to publish date | 02/02/2017 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication of data once all are collected as aggregate data unless we come across some novel genotype -phenotype variations. This will be in peer reviewed journals as well as at international conferences. |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 01/08/2021 | 14/01/2022 | Yes | No |
Editorial Notes
14/01/2022: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
