Correction of Zinc Deficiency in Children With Chronic Kidney Disease and Kidney Transplant

Phase 3

Completed

• Conditions: Trace Element Excess; Zinc Deficiency; Renal Insufficiency, Chronic; Trace Element Deficiency
• Interventions: Drug: Zinc Supplement; Procedure: Repeat blood and urine tests

• Registration Number: NCT02126293
• Lead Sponsor: Hamilton Health Sciences Corporation

Brief Summary

Children with chronic kidney disease, even after transplantation, may be at risk for bone problems due to an imbalance of calcium and phosphorus in the blood, especially as their kidneys progressively fail to function. While some drug and diet treatments are available to prevent such bone disease, many children refuse to take them due to bad taste and tummy cramps. If calcium and phosphorus status remain abnormal for a long time, hard crystals can form in the blood vessels, eventually clogging them and resulting in heart problems. Investigators are studying possible new methods to help the kidneys maintain a normal balance of nutrients in the blood which is important for growing healthy bones and the prevention of side effects in blood vessels that can lead to heart disease. One method is to improve the team work of a hormone FGF-23 and a protein called Klotho that together stimulate the kidneys to increase phosphate removal. Investigators propose that this problem may be due to low blood zinc levels which often occur in children with kidney disease. Thus, in this study, investigators propose to first measure zinc in blood from children with chronic kidney disease (CKD) or who have had kidney transplants to assess zinc and phosphate status, the hormone FGF-23 and its assistant Klotho. If zinc status is low, the children will receive zinc supplementation for 3 months. After treatment with zinc, the same blood measurements will be repeated to determine if the zinc supplements have helped the hormones to remove phosphate from the body. If this pilot project is successful, investigators will then consider a larger scale project involving adult patients as well as pediatric patients from other pediatric centers. This project will also guide investigators as to whether they need to introduce zinc measurements as part of routine testing of CKD and transplant patients. In addition to measuring zinc levels in study participants, trace elements (TE) will also be measured. These include heavy metals such as cadmium, chromium, nickel, vanadium, copper, lead, manganese and selenium. Very little is known about levels and metabolism of TE in CKD especially before dialysis. In adults, cadmium, chromium, nickel, and vanadium probably accumulate in hemodialysis patients, while copper and lead may accumulate. Manganese, selenium are probably deficient. The study will allow investigators to obtain the information about TE in this group of pediatric patients.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-01-30
• Study First Submitted QC: 2014-04-28
• Study First Posted: 2014-04-30
• Study Start: 2014-09
• Primary Completion: 2017-01
• Study Completion: 2017-01
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-10
• Last Update Posted: 2017-03-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Children between 4 and 18 years of age; diagnosis of CKD; renal transplant recipient with declining renal function (eGFR<90 ml/min/1.73 m2).

Exclusion Criteria

• Children with CKD or kidney transplant younger than 4 years. Kidney transplant recipients with eGFR>90 ml/min/1.73 m2.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Zinc deficient patients	Zinc Supplement	If the patient is found to be zinc deficient (serum zinc \< 11.5 μmol/L), the family will be contacted by the RA to commence zinc supplement: zinc citrate (Zinc Lozenges, manufactured by Douglas Laboratories Inc, London, ON, Health Canada NPN 80032476) for 3 months. As per the NPN licence the dose is 10 mg (1 lozenge) orally once a day for children age 4-8 years, and 10 mg twice a day for children age 9-18 years. This should give enough time to restore serum zinc to normal in most patients.
Zinc sufficient patients	Repeat blood and urine tests	Zinc sufficient patients will repeat blood and urine tests in 3 month time to compare the changes with intervention arm.

Primary Outcome Measures

Name	Time	Method
Establish proportion of zinc deficient children with chronic kidney disease and kidney transplant, who achieved correction of zinc deficiency after 3 months of zinc therapy	3 months of therapy

Secondary Outcome Measures

Name	Time	Method
TE levels in zinc deficient children with chronic kidney disease and kidney transplant	Baseline and 12 weeks	Establish TE levels in zinc deficient children with chronic kidney disease and kidney transplant. Establish changes in TE levels following correction of zinc deficiency.
Change in parameters of bone metabolism following zinc treatment in zinc deficient patients	Baseline and 3 months	Correlations between various parameters of bone metabolism, kidney function, zinc, FGF-23 and Klotho assessed by a multiple regression model. Change from baseline in FGF-23, Klotho, TE levels and phosphate excretion after zinc therapy analyzed by a paired t-test.
TE levels in zinc sufficient children with chronic kidney disease and kidney transplant	Baselne and 12 weeks	Establish TE levels in zinc sufficient children with chronic kidney disease and kidney transplant. Establish TE levels 12 weeks later as a quality control measure.

Trial Locations

Locations (2)

Children's Hospital, London Health Science Centre University of Western Ontario; 🇨🇦 London, Ontario, Canada

McMaster Children's Hospital; 🇨🇦 Hamilton, Ontario, Canada