Clinical trial NCT03565913: Potential Therapeutic Role of Effervescent Calcium-Magnesium Citrate in Chronic Kidney Disease Stage V
Official title: Potential Therapeutic Role of Effervescent Calcium-Magnesium Citrate in Chronic Kidney Disease Stage V
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: CKD Stage 5
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2018-06-21
Enrollment: 269
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomized into two groups in a parallel design. One group will take EffCaMgCit 15 meq (300 mg) Ca, 10 meq Mg (122 mg) and 45 meq total citrate thrice daily, while the other group will take calcium acetate suspension/solution (CaAcS) 15 meq Ca thrice daily for two years.
Primary purpose: TREATMENT

Brief summary: 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

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

Eligibility criteria: 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.

Primary outcomes:
measure: Serum T50 for CPP
timeFrame: 24 months
Secondary outcomes:
measure: Intracellular muscle magnesium
timeFrame: 24 months
measure: Control of hyperphosphatemia and serum FGF23
timeFrame: 24 months
measure: Parathyroid function and bone turnover
timeFrame: 24 months
Other outcomes:
Locations:
city: Dallas
country: United States
facility: DaVita Dialysis Centers
state: Texas
Study officials:
affiliation: UTSW
name: Henry Quinones, MD
role: PRINCIPAL_INVESTIGATOR
References: