Assessing Bone Calcium Content in Children With Kidney Disease Treated With Two Different Medicines

NCT04120922 | Unknown DMC

• 2 other identifiers: CTU/2014/146CDF-2016-09-038
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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 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).

Conditions

Chronic Kidney Diseases

Keywords

Dialysis; chronic kidney disease stage 3b, 4-5; calcium isotope ratio; bone mineral content; Calcium isotope fractions δ44/42Ca

Outcome Measures

Primary Outcomes (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).

  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 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).

  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.

Study Arms (2)

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.

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.

Other: calcium carbonate; Other: sevelamer carbonate

Interventions

calcium carbonate OTHER

See arm description

calcium carbonate; sevelamer carbonate

sevelamer carbonate OTHER

See arm description

calcium carbonate; sevelamer carbonate

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• University College, London: lead

Study Sites (1)

Great Ormond Street Hospital for Children

London, WC1N 3JH, United Kingdom

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Calcium Carbonate; Sevelamer

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Calcium Compounds; Inorganic Chemicals; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Minerals; Polyamines; Amines; Organic Chemicals

Study Officials

• Rukshana Shroff, MD FRCPCH PhD

  Great Ormond Street Hospital for Children NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A open label, time series trial

Study Record Dates

• First Submitted: September 18, 2019
• First Posted: October 9, 2019
• Study Start: January 7, 2020
• Primary Completion: December 1, 2021
• Study Completion: April 1, 2022
• Last Updated: August 12, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)