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Assessing Bone Calcium Content in Children With Kidney Disease Treated With Two Different Medicines (CAL-BAL)

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: NCT04120922
Recruitment Status : Not yet recruiting
First Posted : October 9, 2019
Last Update Posted : October 9, 2019
Sponsor:
Information provided by (Responsible Party):
University College, London

Brief 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 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 adminstered 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).


Condition or disease Intervention/treatment Phase
Chronic Kidney Diseases Other: calcium carbonate Other: sevelamer carbonate Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: A open label, time series trial
Masking: None (Open Label)
Masking Description: This is a time series open label trial so there is no randomisation or blinding to treatment. All analyses will be performed in a blinded manner and the treating clinicians will be blinded to the results of the calcium isotope ratios until after participants have completed their trial related administration of P-binder.
Primary Purpose: Basic Science
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
Estimated Study Start Date : November 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : June 2021


Arm Intervention/treatment
calcium carbonate

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.

Other: calcium carbonate
See arm description

Other: sevelamer carbonate
See arm description

sevelamer carbonate

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.

Other: calcium carbonate
See arm description

Other: sevelamer carbonate
See arm description




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  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). [ 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. ]
    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).



Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 5-17 years
  2. Must be in stable Chronic Kidney Disease (CKD) stage 4-5 (as per the Kidney Disease Improving Global Outcomes classification) or on dialysis for at least 1 month
  3. 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
  4. 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
  5. Able to give fully informed consent/ assent as applicable.

Exclusion Criteria:

  1. Pre-existing inherited bone disease
  2. Glucocorticoid therapy in the preceding year, or a lifetime cumulative steroid exposure ≥6 months
  3. Bisphosphonate therapy at any time in the past
  4. On cinacalcet in the preceding 6-months
  5. Any acute illness in the preceding 2 weeks (when the child was unable to maintain their usual diet or had bed-rest)
  6. Living-donor renal transplant planned ≤6 months
  7. At screening the albumin-corrected serum calcium cannot be <2.0mMol/L or >2.8mMol/L
  8. Already participating in any interventional clinical trial or last trial completed less than 4 weeks previously
  9. Previously documented poor compliance with medications
  10. Any other contraindication to usual prescription of calcium carbonate or sevelamer carbonate
  11. Pregnant or lactating
  12. Currently on sevelamer (includes sevelamer carbonate or sevelamer hydrochloride)

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): NCT04120922


Contacts
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Contact: Dr Rukshana Shroff, Consultant Paediatric Nephrologist, MD FRCPCH PhD 020 7405 9200 ext 8513/0292 Rukshana.Shroff@gosh.nhs.uk

Sponsors and Collaborators
University College, London
Investigators
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Principal Investigator: Rukshana Shroff, MD FRCPCH PhD Great Ormond Street Hospital for Children NHS Foundation Trust

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Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT04120922    
Other Study ID Numbers: CTU/2014/146
CDF-2016-09-038 ( Other Grant/Funding Number: NIHR )
First Posted: October 9, 2019    Key Record Dates
Last Update Posted: October 9, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University College, London:
Dialysis
chronic kidney disease stage 4-5
calcium isotope ratio
bone mineral content
Calcium isotope fractions δ44/42Ca
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Calcium, Dietary
Calcium Carbonate
Calcium
Sevelamer
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Bone Density Conservation Agents
Antacids
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Agents
Chelating Agents
Sequestering Agents