Potential Therapeutic Role of Effervescent Calcium-Magnesium Citrate in Chronic Kidney Disease Stage V

The Investigators plan to conduct a long-term trial to explore therapeutic implications of effervescent calcium magnesium citrate (EffCaMgCit) in CKD Stage V (end stage renal disease on hemodialysis). The Investigators will test the hypothesis that EffCaMgCit would retard the formation of calciprotein particles (CPP) in CKD Stage V, thereby reducing the degree of coronary artery and peripheral artery calcification and cardiac hypertrophy-fibrosis.

Aim 1. To compare cardiovascular risk of EffCaMgCit versus CaAcS in CKD Stage V Aim 2. To show that EffCaMgCit reduces putative serum FGF23, and increases beneficial alkali load Aim 3. To compare parameters of bone turnover and bone mineral density (BMD) between EffCaMgCit and CaAcS groups

Study Overview

• Status: Recruiting
• Conditions: CKD Stage 5
• Intervention / Treatment: Drug: EffCaMgCit; Other: CaAcS

Detailed Description

150 adult subjects (> 21 years of age, any cause of CKD) of either gender of any ethnicity with CKD Stage V on hemodialysis will be recruited from Davita-UTSW dialysis centers and randomized into two equal groups in a parallel design, stratified according to gender and age (> or ≤ 50 years). After baseline evaluation, one group (EffCaMgCit Group) will take EffCaMgCit, and the other group (CaAcS Group) will take calcium acetate suspension/solution for two years. Both drugs will be taken 1 sachet each just before or along with breakfast and dinner for the first three months. If tolerated, the dose will be increased to 1 sachet tid just before or along with breakfast, lunch and dinner.

After screening and a baseline evaluation, research personnel will visit patients at the dialysis center every three months for two years. Patients will be evaluated with a medical history, side effect questionnaires, blood pressure measurements, blood tests, echocardiograms, coronary artery calcification analyses, muscle magnesium analyses, and bone mineral density analyses.

It is expected that markers of cardiovascular risk would be improved in patients taking CaMgCit, and would remain stable in those taking CaAcS.

Endpoint Expectations:

• During treatment with EffCaMgCit, T50 would increase (indicative of reduced propensity for CPP formation)
• Serum Mg (inhibitor of CPP formation) would be increased by EffCaMgCit
• An increase in intracellular muscle Mg would show that EffCaMgCit provides a Mg load, and also indicates repletion of Mg stores that might be cardioprotective independently of effects on CPP formation
• The Investigators anticipate that serum FGF23 would be lower and serum Klotho would be higher on EffCaMgCit

• Study Type: Interventional
• Enrollment (Estimated): 245
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Miranda King, MPH; Phone Number: 214-648-2117; Email: Miranda.King@utsouthwestern.edu
• Study Contact Backup: Name: Henry Quinones, MD; Phone Number: 214-645-6414; Email: Henry.Quinones@utsouthwestern.edu

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75224
      • Recruiting
      • DaVita Dialysis Centers

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult subjects (> 21 years of age, any cause of CKD) of either gender of any ethnicity with CKD Stage V on hemodialysis will be recruited. Patients with Type II diabetes and hypertension will be allowed. Treatment with drugs for management of osteoporosis (bisphosphonate, teriparatide, or denosumab) or for chronic kidney disease, customary drugs for hypertension or diabetes, and exogenous estrogen or selective estrogen receptor modulators will be allowed.

Exclusion Criteria:

• Patients with serum Mg > 3.65 mg/dL (3 meq/L) will be excluded (de Francisco, 2010). Also excluded from the study will be those with bowel disease, hypercalcemia, hypophosphatemia (serum P < 2.5 mg/dL) and treatment with adrenocorticosteroids or aluminum-containing antacids or drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EffCaMgCit; Patients in the EffCaMgCit group will receive 45 meq (900 mg) Ca, 30 meq (365 mg) Mg, and 135 meq total citrate per day from 3 months to 2 years.	Drug: EffCaMgCit; Patients in the EffCaMgCit group will receive 45 meq (900 mg) Ca, 30 meq (365 mg) Mg, and 135 meq total citrate per day from 3 months to 2 years.; Other Names: Effervescent calcium magnesium citrate
Active Comparator: CaAcS; Patients in the CaAcS group will take 45 meq (900 mg) Ca and 45 meq acetate (without Mg or citrate) per day.	Other: CaAcS; CaAcS group will take 45 meq (900 mg) Ca and 45 meq acetate (without Mg or citrate), three times daily for 2 years; Other Names: Calcium acetate suspension/solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum T50 for CPP	The maturation time (T50) of calciprotein particles in serum will be measured. T50 CPP (measured by Calcisco using Pasch's method) assays the kinetics of transformation from primary to secondary CPP in vitro. Fresh serum samples will be kept at -80 degrees until shipment to Calcisco AG (Berne, Switzerland) for T50 analysis, which will determine T50 of CPP through research collaboration with CMMCR.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracellular muscle magnesium	Intracellular Mg will be measured in calf muscle, by using 31P magnetic resonance spectroscopy, based on the formula: [Mg] - kd(10.796-D)/(D-8.251), in which kd is the dissociation constant for MgATP complex (=50 µM) and D is the chemical shift difference between alpha- and beta-ATP 31P signals observed in 31P MR spectrum.	24 months
Control of hyperphosphatemia and serum FGF23	The control of hyperphosphatemia will be evaluated from changes in serum P concentration, serum FGF23 and Klotho.	24 months
Parathyroid function and bone turnover	Parathyroid function will be evaluated from serum PTH, vitamin D status from serum calcitriol, bone resorption from serum CTX, and bone formation from serum BSAP. Change in bone mass will be evaluated by BMD (proximal femur, L2-L4 spine and distal third of radius).	24 months

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Henry Quinones, MD, UTSW

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2017
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: May 18, 2018
• First Submitted That Met QC Criteria: June 11, 2018
• First Posted (Actual): June 21, 2018

Study Record Updates

• Last Update Posted (Actual): October 13, 2023
• Last Update Submitted That Met QC Criteria: October 11, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Chelating Agents; Sequestering Agents; Cathartics; Calcium; Calcium, Dietary; Calcium acetate; Magnesium citrate
• Other Study ID Numbers: STU 122016-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No