The Effect of Sodium Bicarbonate (Nephrotrans®) on Calcification Propensity of Serum in Kidney Transplant Recipients

Study Overview
=================
Brief Summary
-----------------
This is a single-center, prospective, open-label, randomized, cross-over study.

Detailed Description
-----------------
The primary hypothesis (H1) is that the T50 value will change between wash-out and high-dose (3000mg/d) sodium bicarbonate (Nephrotrans®) substitution. The 0-hypothesis (H0) is that substitution of 3000 mg/d sodium bicarbonate (Nephrotrans®) has no effect on T50-values as compared to wash-out-phase. Patients will be randomized in a 1:1 ratio to either receive low-dose (1500 mg/d) sodium bicarbonate followed by high-dose (3000mg/d) sodium bicarbonate (sequence A-B) or to receive high-dose sodium bicarbonate followed by low-dose sodium bicarbonate (sequence B-A) with washout-phases in between. Patients will be randomized in a 1:1 ratio to either receive low-dose (1500 mg/d) sodium bicarbonate followed by high-dose (3000mg/d) sodium bicarbonate (sequence A-B) or to receive high-dose sodium bicarbonate followed by low-dose sodium bicarbonate (sequence B-A) with washout-phases in between. The study will start with an initial run-in wash-out phase, where all sodium bicarbonate or other alkalizing treatment taken by the patient as standard of care will be discontinued. Consequently, there will be a sodium bicarbonate treatment (high dose/low dose) phase, followed by a wash-out phase, followed by another sodium bicarbonate treatment (high dose/low dose) phase, followed by a final wash-out phase. Each study phase, including wash-out phases as well as low-dose and high-dose treatment phases will be 14 ±3 days of duration. Patients will be followed up to 12weeks after randomization until the last study visit of the final wash-out phase.

Official Title
-----------------
The Effect of Sodium Bicarbonate (Nephrotrans®) on Calcification Propensity of Serum in Kidney Transplant Recipients

Conditions
-----------------
Kidney Transplant; Complications

Intervention / Treatment
-----------------
* Drug: Low dose sodium bicarbonate
* Drug: High dose sodium bicarbonate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults ≥ 18 years old Prevalent (≥ 6 months after kidney transplantation) kidney transplant recipients eGFR (CKD-EPI formula) between 10 and 50 ml/min/1.73 m² Patient has provided informed consent prior to initiation of any study related procedure Exclusion Criteria: Allergy to sodium bicarbonate or any component of Nephrotrans®, namely soy or peanuts (reported cross-reactivity to peanuts has been reported in patients with soy-allergy). Unstable clinical condition (e.g. uncontrolled heart failure, clinical uremia, uncontrolled hypertension, impending initiation of dialysis treatment…) as judged by the recruiting physician Pregnant and nursing (lactating) women Unwillingness to discontinue current medication with sodium bicarbonate Unwillingness to discontinue antacids containing aluminum, calcium carbonate, magnesium, lactate, citrate, bicarbonate or mixtures thereof

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Patients will be randomized in a 1:1 ratio to either receive low-dose (1500 mg/d) sodium bicarbonate followed by high-dose (3000mg/d) sodium bicarbonate (sequence A-B) or to receive high-dose sodium bicarbonate followed by low-dose sodium bicarbonate (sequence B-A) with washout-phases in between.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low dose sodium bicarbonate<br>Low dose 1500 mg sodium bicarbonate (Nephrotrans®) per day (500mg tablets 3x/day) for 14 ± 3 days. The patients will be advised to take one capsule with breakfast, one with lunch and one with dinner (schedule 1-1-1). | Drug: Low dose sodium bicarbonate<br>* 1500 mg sodium bicarbonate<br>* Other names: Nephrotrans;|
| Active Comparator: High Dose sodium bicarbonate<br>High dose 3000 mg of sodium bicarbonate (Nephrotrans®) per day (500mg tablets 3x/day) for 14 ± 3 days. The patients will be advised to take two capsules with breakfast, two with lunch and two with dinner (schedule 2-2-2). | Drug: High dose sodium bicarbonate<br>* 3000 mg sodium bicarbonate<br>* Other names: Nephrotrans;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Propensity of serum for calcification | The primary outcome is change in the mean T50 values between different study phases (treatment vs. control). | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum bicarbonate levels | The secondary outcome is change of serum bicarbonate levels between different study phases. | 12 weeks |