The Effect of Sevelamer Carbonate on Serum Trimethylamine-n-Oxide (TMAO) Level in Patients With Chronic Kidney Disease (CKD) Stage 3b-4

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to investigate effects of sevelamer carbonate on reducing TMAO in stage 3b-4 CKD (pre-dialysis) patients. The study will also investigate the safety and tolerability of sevelamer carbonate in study population and the effects of sevelamer carbonate on serum p-cresyl sulfate, indoxyl sulfate, LDL-C and uric acid.

Official Title
-----------------
The Effect of Sevelamer Carbonate on Serum Trimethylamine-n-Oxide (TMAO) Level in Patients With Chronic Kidney Disease (CKD) Stage 3b-4: a Protocol of a Randomized, Parallel, Controlled Trial

Conditions
-----------------
CKD Stage 3b, CKD Stage 4

Intervention / Treatment
-----------------
* Drug: Sevelamer Carbonate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Men or women, aged from 18 to 75 years old; 2. Provide informed consent prior to enrolling in the study; 3. Estimated glomerular filtration rate (eGFR) between 15-45 ml/min/1.73 m2 (calculated by CKD-EPI equation) Exclusion Criteria: 1. Documented poorly controlled diabetes mellitus, poorly controlled hypertension, malignant tumour, or any clinically significant unstable medical condition; 2. Active dysphagia or swallowing disorder; or a predisposition to or current bowel obstruction, ileus, or severe gastrointestinal motility disorders including severe constipation; 3. Known hypersensitivity to sevelamer or any constituents of the study drug; 4. Unable to comply with the requirements of the study; 5. Hypophosphatemia (serum phosphorus level <0.87mmol/L); 6. Women who have a positive pregnancy test at enrollment or women who are breast-feeding; 7. Have been enrolled in other interventional study; 8. Received sevelamer or other intestinal adsorbents, or broad-spectrum antibiotic within one month prior to the screening period.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sevelamer Carbonate<br>Sevelamer carbonate will be given with fixed dose of 1600mg (p.o. b.i.d) with meals | Drug: Sevelamer Carbonate<br>* Sevelamer carbonate 1600mg (p.o. b.i.d) with meals<br>|
| No Intervention: Control<br>blank-control | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in the serum concentration of TMAO between treatment group and control group | The serum concentration of TMAO will be evaluated by high performance liquid chromatography (HPLC) | 22 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in the serum concentration of p-cresyl sulfate between treatment group and control group | The serum concentration of p-cresyl sulfate will be evaluated by high performance liquid chromatography (HPLC) | 22 weeks | 
| Difference in the serum concentration of indoxyl sulfate between treatment group and control group | The serum concentration of indoxyl sulfate will be evaluated by high performance liquid chromatography (HPLC) | 22 weeks | 
| Difference in the serum concentration of LDL-C between treatment group and control group | Chemistry evaluations | 22 weeks | 
| Difference in the serum concentration of uric acid between treatment group and control group | Chemistry evaluations | 22 weeks |