Chronic Kidney DiseasesCAL-BALNCT04120922
Assessing Bone Calcium Content in Children With Kidney Disease Treated With Two Different Medicines
A study testing calcium carbonate and sevelamer carbonate in people with Chronic Kidney Diseases, run by University College, London at 1 site in United Kingdom.
Trial summary
This is an open label, time series trial. The trial is likely to be single centre (additional sites will only be opened if necessary) and will involve 25 children with chronic kidney disease (stage 3b, 4-5) or on dialysis. Read more about this study
- Who is it for?
- Ages 5 to 17 years
- Conditions the study is for
- Chronic Kidney Diseases
- What is being tested?
- calcium carbonate and sevelamer carbonate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 7 Jan 2020to Apr 2022
- Phase
- Interventional
- 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 5 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age 5-17 years
- Must be in stable Chronic Kidney Disease (CKD) stage 3b-5 (as per the Kidney Disease Improving Global Outcomes classification) or on dialysis for at least 1 month
- Hyperphosphataemia defined as a serum P above the age-specific normal level as per the Kidney Disease Outcomes Quality Initiative (KDOQI) guideline, or high or normal P levels in a patient already on a P-binder in the preceding 4 weeks
- On a stable Ca and P diet as assessed by a dietitian and willing to avoid intentional changes in their dairy intake during the trial period
- Able to give fully informed consent/ assent as applicable.
Who cannot join
- Pre-existing inherited bone disease
- Glucocorticoid therapy in the preceding year, or a lifetime cumulative steroid exposure ≥6 months
- Bisphosphonate therapy at any time in the past
- On cinacalcet in the preceding 6-months
- Any acute illness in the preceding 2 weeks (when the child was unable to maintain their usual diet or had bed-rest)
- Living-donor renal transplant planned ≤6 months
Show all 14Show fewer
- At screening the albumin-corrected serum calcium cannot be <2.0mMol/L or >2.8mMol/L
- Already participating in any interventional clinical trial or last trial completed less than 4 weeks previously
- Previously documented poor compliance with medications
- Any other contraindication to usual prescription of calcium carbonate or sevelamer carbonate
- Any other reason in the opinion of the Investigator that the participant may not be suitable
- Estimated GFR (eGFR) more than 45ml/min/1.73m2
- Pregnant or lactating
- Currently on sevelamer (includes sevelamer carbonate or sevelamer hydrochloride)
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Great Ormond Street Hospital for Children
London, WC1N 3JH
About this study
Official title: The Effect of Calcium-based and Calcium-free Phosphate-binders on Bone Mineral Content, Measured by a Novel Technique of Dual-tracer Stable Calcium Isotope Method, in Children With Chronic Kidney Disease or on Dialysis - a Time Series Trial
This is an open label, time series trial. The trial is likely to be single centre (additional sites will only be opened if necessary) and will involve 25 children with chronic kidney disease (stage 3b, 4-5) or on dialysis. The overall aim of this trial is to explore the viability of the Ca isotope ratio measured by dual-tracer stable Ca isotope method as a measure of bone mineral (Ca) content, and to evaluate how it changes in response to two commonly used medications that either contain Ca (calcium carbonate) or do not (sevelamer carbonate). Both calcium carbonate and sevelamer carbonate are routinely used in children, but their effect on the bone mineral content (measured by the Ca isotope ratio) has not been studied.
This short-term trial will provide proof-of-concept data to determine the utility of the Ca isotope fractionation technique in guiding medication usage in children with CKD and on dialysis. These data will inform a potential future randomised trial that utilises the calcium isotope fractionation technique to adjust the calcium intake (through diet and different medications, including vitamin D analogues) and monitor changes in important patient level outcomes such as fractures and bone mineral density on DXA scan.
Read more
Participants will be administered sevelamer carbonate first for 16 weeks and then will switch to calcium carbonate for 12 weeks. Participants may need to change medication earlier than 16 weeks at the clinician's discretion based on their calcium levels on routine blood tests.
Calcium isotope levels will be measured in blood and urine samples for up to 28 weeks. Isotopes levels in faeces and dialysis fluid samples may also be measured.
This is not a Clinical Trial of an Investigational Medicinal Product (CTIMP).
Read the detailed description
Lay Summary of Background and Rationale:
The growing bones of children need calcium in order to mineralise (become strong). Children with kidney failure (called chronic kidney disease; CKD) or on dialysis can often be calcium deficient. They are given medications with extra calcium to help their bones mineralise. However, there is currently no practical way of measuring bone mineralisation. Doctors may perform special x-rays, but it takes many months before any bone structure problems become apparent on X-rays. Doctors giving children additional calcium do not know how much to give. Sometimes children are given too little and their bones do not mineralise adequately, or they are given too much, and the excess calcium is deposited in their arteries causing vascular calcification. Timely and practical ways of measuring bone mineralisation are needed so doctors can accurately determine the amount of calcium containing medicines they give.
The CAL-BAL trial will evaluate a novel potential biomarker of bone mineralisation: the calcium isotope ratio (δ44/42Ca) which will be measured in blood and urine. The trial will collect information on δ44/42Ca for patients with CKD or on dialysis for 28 weeks. It will measure how δ44/42Ca changes when a patient switches from a medicine containing calcium to one not containing calcium. It will also evaluate the association between δ44/42Ca and established biomarkers of bone formation and repair.
The data collected in CALBAL will not by itself allow doctors to decide whether δ44/42Ca is good biomarker of bone mineralisation. However, it will provide additional biological and clinical information that will further clarify its usefulness as biomarker for further research. Together with information from previous studies done by the Chief Investigator which measured the typical δ44/42Ca of healthy children and children with CKD and on dialysis, the data collected in CAL-BAL may inform the design of a future randomised trial of standard-of-care compared to an approach where δ44/42Ca results are used to prescribe the amount of medicine containing calcium children with CKD or on dialysis are given.
- Conditions
- Chronic Kidney Diseases
- Being tested
- calcium carbonate, sevelamer carbonate
- Keywords
- Dialysis, chronic kidney disease stage 3b, 4-5, calcium isotope ratio, bone mineral content, Calcium isotope fractions δ44/42Ca
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
calcium carbonateOther
See arm description
sevelamer carbonateOther
See arm description
| Study group | Role | What they receive |
|---|---|---|
| calcium carbonate | Other | Calcium based P-binder - calcium carbonate: Typical dose is 500mg, orally, three times a day but this can be adjusted as per individual patient requirements at the clinician's discretion.
All participants will be given sevelamer carbonate (Ca-free P-binder) for up to 16 weeks and then calcium carbonate (Ca-based P-binder) for 12 weeks, administered orally. No wash out period is possible as the children must always be on a P-binder. The Ca-free P-binder may be administered for less than 16 weeks if it is clinically necessary to resume the Ca-based P-binder early based on serial monitoring of serum Ca levels. Receives: Other: calcium carbonate; Other: sevelamer carbonate |
| sevelamer carbonate | Other | Calcium (Ca) free P-binder - sevelamer carbonate: Typical dose is 800mg, orally, three times a day but this can be adjusted as per individual patient requirements at the clinician's discretion.
All participants will be given sevelamer carbonate (Ca-free P-binder) for up to 16 weeks and then calcium carbonate (Ca-based P-binder) for 12 weeks, administered orally. No wash out period is possible as the children must always be on a P-binder. The Ca-free P-binder may be administered for less than 16 weeks if it is clinically necessary to resume the Ca-based P-binder early based on serial monitoring of serum Ca levels. Receives: Other: calcium carbonate; Other: sevelamer carbonate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ca isotope ratios in serum measured by dual-tracer stable isotope method (Ca isotope fractions δ44/42Ca) of a child after up to 12 weeks treatment with each of two P-binders (Ca based and Ca free).
Ca isotope ratios in serum measured by dual-tracer stable isotope method (Ca isotope fractions δ44/42Ca) of a child after up to 12 weeks treatment with each of two P-binders (Ca based and Ca free).
Measured: Measured over 12 weeks. N.B. Treatment changes from sevelamer carbonate to calcium carbonate after 16 weeks in the trial or earlier at the clinician's discretion based on serial monitoring of serum Ca levels.
Secondary outcomes (1)
Ca isotope ratios in urine measured by dual-tracer stable Ca isotope method (Ca isotope fractions δ44/42Ca) of a child after up to 12 weeks treatment with each of two P-binders (Ca based and Ca free).
To evaluate the association between the change in δ44/42Ca in blood and urine during treatment with each P-binder with the following quantities (which will also be measured longitudinally):1. Dietary Ca and vitamin D intake (including Ca intake from phosphate binders) 2. Serum Ca, P, PTH, 25(OH)D and 1,25(OH)2D 3. Biomarkers of osteoblast (bone-specific alkaline phosphatase, P1NP), osteoclast (TRAP5b, carboxyterminal cross - linked telopeptide of type I collagen- CTX and NTX), and osteocyte activity (FGF23, sclerostin). 4.To determine the earliest detectable changes in Ca isotope ratios after changing therapy. In children on haemodialysis the Ca isotope ratios will be measured by dual-tracer stable Ca isotope method (Ca isotope fractions δ44/42Ca) in serum and urine (if available) at day 3, day 5, day 8 and day 10 (+/- 2 days) after starting sevelamer carbonate or calcium carbonate.
Measured: Measured over 12 weeks. N.B. Treatment changes from sevelamer carbonate to calcium carbonate after 16 weeks in the trial or earlier at the clinician's discretion based on serial monitoring of serum Ca levels.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2019
- Study start7 Jan 2020
- Primary completionDec 2021 (estimated)
- Study completionApr 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Kidney DiseasesStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- A open label, time series trial
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rukshana Shroff, MD FRCPCH PhD, Principal investigator, Great Ormond Street Hospital for Children NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04120922
- Sponsor's protocol ID
- CTU/2014/146
- Other IDs
- CDF-2016-09-038
- Acronym
- CAL-BAL
- Status last verified
- Aug 2021
- First submitted
- 18 Sep 2019
- Last updated
- 12 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- 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 12 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Calcium-based and Calcium-free Phosphate-binders on Bone Mineral Content, Measured by a Novel Technique of Dual-tracer Stable Calcium Isotope Method, in Children With Chronic Kidney Disease or on Dialysis - a Time Series Trial
- ClinicalTrials.gov ID
- NCT04120922
- Acronym / sponsor ID
- CAL-BAL / CTU/2014/146
- Conditions
- Chronic Kidney Diseases
- Keywords
- Dialysis, chronic kidney disease stage 3b, 4-5, calcium isotope ratio, bone mineral content, Calcium isotope fractions δ44/42Ca
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 21 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- 7 Jan 2020 (actual)
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Apr 2022 (estimated)
- First posted
- 9 Oct 2019 (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.
This is an open label, time series trial. The trial is likely to be single centre (additional sites will only be opened if necessary) and will involve 25 children with chronic kidney disease (stage 3b, 4-5) or on dialysis. The overall aim of this trial is to explore the viability of the Ca isotope ratio measured by dual-tracer stable Ca isotope method as a measure of bone mineral (Ca) content, and to evaluate how it changes in response to two commonly used medications that either contain Ca (calcium carbonate) or do not (sevelamer carbonate). Both calcium carbonate and sevelamer carbonate are routinely used in children, but their effect on the bone mineral content (measured by the Ca isotope ratio) has not been studied.
This short-term trial will provide proof-of-concept data to determine the utility of the Ca isotope fractionation technique in guiding medication usage in children with CKD and on dialysis. These data will inform a potential future randomised trial that utilises the calcium isotope fractionation technique to adjust the calcium intake (through diet and different medications, including vitamin D analogues) and monitor changes in important patient level outcomes such as fractures and bone mineral density on DXA scan.
Participants will be administered sevelamer carbonate first for 16 weeks and then will switch to calcium carbonate for 12 weeks. Participants may need to change medication earlier than 16 weeks at the clinician's discretion based on their calcium levels on routine blood tests.
Calcium isotope levels will be measured in blood and urine samples for up to 28 weeks. Isotopes levels in faeces and dialysis fluid samples may also be measured.
This is not a Clinical Trial of an Investigational Medicinal Product (CTIMP).
Detailed description
Lay Summary of Background and Rationale:
The growing bones of children need calcium in order to mineralise (become strong). Children with kidney failure (called chronic kidney disease; CKD) or on dialysis can often be calcium deficient. They are given medications with extra calcium to help their bones mineralise. However, there is currently no practical way of measuring bone mineralisation. Doctors may perform special x-rays, but it takes many months before any bone structure problems become apparent on X-rays. Doctors giving children additional calcium do not know how much to give. Sometimes children are given too little and their bones do not mineralise adequately, or they are given too much, and the excess calcium is deposited in their arteries causing vascular calcification. Timely and practical ways of measuring bone mineralisation are needed so doctors can accurately determine the amount of calcium containing medicines they give.
The CAL-BAL trial will evaluate a novel potential biomarker of bone mineralisation: the calcium isotope ratio (δ44/42Ca) which will be measured in blood and urine. The trial will collect information on δ44/42Ca for patients with CKD or on dialysis for 28 weeks. It will measure how δ44/42Ca changes when a patient switches from a medicine containing calcium to one not containing calcium. It will also evaluate the association between δ44/42Ca and established biomarkers of bone formation and repair.
The data collected in CALBAL will not by itself allow doctors to decide whether δ44/42Ca is good biomarker of bone mineralisation. However, it will provide additional biological and clinical information that will further clarify its usefulness as biomarker for further research. Together with information from previous studies done by the Chief Investigator which measured the typical δ44/42Ca of healthy children and children with CKD and on dialysis, the data collected in CAL-BAL may inform the design of a future randomised trial of standard-of-care compared to an approach where δ44/42Ca results are used to prescribe the amount of medicine containing calcium children with CKD or on dialysis are given.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- A open label, time series trial
| Arm | Type | Receives |
|---|---|---|
| calcium carbonate | Other | Other: calcium carbonate, Other: sevelamer carbonateCalcium based P-binder - calcium carbonate: Typical dose is 500mg, orally, three times a day but this can be adjusted as per individual patient requirements at the clinician's discretion. All participants will be given sevelamer carbonate (Ca-free P-binder) for up to 16 weeks and then calcium carbonate (Ca-based P-binder) for 12 weeks, administered orally. No wash out period is possible as the children must always be on a P-binder. The Ca-free P-binder may be administered for less than 16 weeks if it is clinically necessary to resume the Ca-based P-binder early based on serial monitoring of serum Ca levels. |
| sevelamer carbonate | Other | Other: calcium carbonate, Other: sevelamer carbonateCalcium (Ca) free P-binder - sevelamer carbonate: Typical dose is 800mg, orally, three times a day but this can be adjusted as per individual patient requirements at the clinician's discretion. All participants will be given sevelamer carbonate (Ca-free P-binder) for up to 16 weeks and then calcium carbonate (Ca-based P-binder) for 12 weeks, administered orally. No wash out period is possible as the children must always be on a P-binder. The Ca-free P-binder may be administered for less than 16 weeks if it is clinically necessary to resume the Ca-based P-binder early based on serial monitoring of serum Ca levels. |
Who may qualify
- Ages
- 5 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Age 5-17 years
- Must be in stable Chronic Kidney Disease (CKD) stage 3b-5 (as per the Kidney Disease Improving Global Outcomes classification) or on dialysis for at least 1 month
- Hyperphosphataemia defined as a serum P above the age-specific normal level as per the Kidney Disease Outcomes Quality Initiative (KDOQI) guideline, or high or normal P levels in a patient already on a P-binder in the preceding 4 weeks
- On a stable Ca and P diet as assessed by a dietitian and willing to avoid intentional changes in their dairy intake during the trial period
- Able to give fully informed consent/ assent as applicable.
Key exclusion criteria (14 listed)
- Pre-existing inherited bone disease
- Glucocorticoid therapy in the preceding year, or a lifetime cumulative steroid exposure ≥6 months
- Bisphosphonate therapy at any time in the past
- On cinacalcet in the preceding 6-months
- Any acute illness in the preceding 2 weeks (when the child was unable to maintain their usual diet or had bed-rest)
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 |
|---|---|---|
| calcium carbonateSee arm description | Other | calcium carbonate, sevelamer carbonate |
| sevelamer carbonateSee arm description | Other | calcium carbonate, sevelamer carbonate |
Primary outcome
Ca isotope ratios in serum measured by dual-tracer stable isotope method (Ca isotope fractions δ44/42Ca) of a child after up to 12 weeks treatment with each of two P-binders (Ca based and Ca free).
Time frame: Measured over 12 weeks. N.B. Treatment changes from sevelamer carbonate to calcium carbonate after 16 weeks in the trial or earlier at the clinician's discretion based on serial monitoring of serum Ca levels.
Ca isotope ratios in serum measured by dual-tracer stable isotope method (Ca isotope fractions δ44/42Ca) of a child after up to 12 weeks treatment with each of two P-binders (Ca based and Ca free).
1 secondary outcome
Ca isotope ratios in urine measured by dual-tracer stable Ca isotope method (Ca isotope fractions δ44/42Ca) of a child after up to 12 weeks treatment with each of two P-binders (Ca based and Ca free).
Time frame: Measured over 12 weeks. N.B. Treatment changes from sevelamer carbonate to calcium carbonate after 16 weeks in the trial or earlier at the clinician's discretion based on serial monitoring of serum Ca levels.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2021.
- Individual participant dataSharing planned: No
Related trials for Chronic Kidney Diseases
Active, not recruitingPhase 2
Safety and Efficacy of Empagliflozin in Hemodialysis
End Stage Renal Disease
RecruitingPhase 3
Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN
Berger Disease, Bergers Disease
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Not yet recruiting
An Individuation Intervention to Reduce Socioeconomic Disparities in Chronic Kidney Disease Care
Chronic Kidney Diseases
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.
Rukshana Shroff, MD FRCPCH PhD principal investigator
Great Ormond Street Hospital for Children NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing calcium carbonate and sevelamer carbonate in people with Chronic Kidney Diseases, run by University College, London at 1 site in United Kingdom.
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 5 inclusion and 14 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 12 Aug 2021. 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 United Kingdom. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ca isotope ratios in serum measured by dual-tracer stable isotope method (Ca isotope fractions δ44/42Ca) of a child after up to 12 weeks treatment with each of two P-binders (Ca based and Ca free). (time frame: Measured over 12 weeks. N.B. Treatment changes from sevelamer carbonate to calcium carbonate after 16 weeks in the trial or earlier at the clinician's discretion based on serial monitoring of serum Ca levels.). 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 12 Aug 2021.