Clinical trial NCT06398002: The Effect of Increasing Dialysate Calcium on T50 in Subjects With Secondary Hyperparathyroidism and ESKD
Official title: The Effect of Increasing Dialysate Calcium on Serum Calcification Propensity in Subjects With Secondary Hyperparathyroidism and End-Stage Kidney Disease
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Secondary Hyperparathyroidism
End-stage Kidney Disease
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
First posted: 2024-05-03
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised, double-blind, parallel-group, controlled clinical trial
Primary purpose: TREATMENT

Brief summary: Patients with end-stage kidney disease (ESKD) have an increased risk of cardiovascular mortality. High parathyroid hormone (PTH) from secondary hyperparathyroidism leads to increased efflux of phosphate and calcium from bone, which exacerbates vascular calcification and increases the risk of bone fractures. The main driving factor for secondary hyperparathyroidism is hypocalcaemia caused by low levels of 1,25-dihydroxy vitamin D and pharmacological supplementation with activated vitamin D and oral calcium-containing phosphate-binders are used to control secondary hyperparathyroidism. The amount of calcium used in this context is controversial, as higher calcium load in blood may theoretically increase vascular calcification. Conversely, by alleviating the efflux of phosphate and calcium from bone due to secondary hyperparathyroidism, increasing the load of calcium might actually prevent vascular calcification.

To study this further, we wish to conduct a randomised double-blinded controlled clinical trial of increasing dialysate Ca from 1.25 mmol/L (standard dialysate concentration) to 1.50 mmol/L in patients with ESKD and secondary hyperparathyroidism on maintenance haemodialysis (HD). The overall effect of increased dialysate calcium will be gauged by its effect on serum calcification propensity (T50) and on markers of bone turnover.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years.
* Treatment with thrice-weekly maintenance HD for ESKD for \> 3 months.
* Dialysate calcium of 1.25 mmol/L (standard concentration).
* Plasma ionised calcium \< 1.35 mmol/L (average of last 3 months).
* Plasma intact PTH \> 14 ρmol/L.
* Plasma total alkaline phosphatase \>90 U/L
* Negative pregnancy test and use of highly effective and safe contraception.
* Able to give written informed consent.

Exclusion Criteria:

* Treatment with peritoneal dialysis.
* Clinical bone fracture within the last 6 months.
* Treatment with bisphosphonates, denosumab, romosozumab, or teriparatide within the last 3 months.
* Other diseases or conditions, which, in the opinion of the site investigator, would prevent participation in or completion of the trial.
* Pregnancy or breastfeeding.

Primary outcomes:
measure: Difference in serum calcification propensity (T50)
timeFrame: 28 days
Secondary outcomes:
measure: Difference in bone-specific alkaline phosphatase (bALP)
timeFrame: 28 days
measure: Difference in procollagen 1 intact N-terminal propeptide (P1NP)
timeFrame: 28 days
measure: Difference in tartrate-resistant acid phosphatase 5b (TRAcP 5b)
timeFrame: 28 days
measure: Difference in parathyroid hormone (PTH)
timeFrame: 28 days
measure: Difference in calciprotein monomers (CPM)
timeFrame: 28 days
measure: Difference in primary calciprotein particles (CPP-1)
timeFrame: 28 days
measure: Difference in primary calciprotein particles (CPP-2)
timeFrame: 28 days
measure: Difference in plasma ionised calcium (iCa)
timeFrame: 28 days
measure: Difference in plasma phosphate (PO4)
timeFrame: 28 days
measure: Difference in plasma magnesium (Mg)
timeFrame: 28 days
measure: Difference in all above variables
timeFrame: 28 days
Other outcomes:
Locations:
Study officials:
affiliation: Herlev and Gentofte Hospital
name: Iain Bressendorff, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: