Dextromethorphan and Silymarin in Chronic Kidney Disease (CKD) Patients

Study Overview
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Brief Summary
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The investigators test the renal and cardiovascular protective effects dextromethorphan and silymarin on patients with the proteinuric chronic kidney diseases, who enrolled in our clinical trial, had progressing kidney diseases and merit aggressive anti-inflammatory therapy.

Official Title
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The Reno-protective and Cardiovascular Effect of Dextromethorphan and Silymarin in Patients With Chronic Kidney Disease

Conditions
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Proteinuria

Intervention / Treatment
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* Drug: Dextromethorphan
* Drug: Silymarin
* Drug: sugar pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Stage 3 or 4 chronic kidney disease as measured by a Modification in Diet in Renal Disease Study (MDRD) estimate of between 15 ml/min and 59 ml/min and and 0.5 g/day<proteinuria<3g/day. Age between 18 and 75 years old. Patients without hospitalization for cardiac or infection related morbidity over the previous 2 months(due to the potential confounding effects on baseline study variables). Patients who are able to provide consent to participate in the study.- Exclusion Criteria: patients will significant mental illness, pregnant women, and other vulnerable populations. Patients with active hepatic disease and/or ALT > 2.5 times upper limit of normal. Patients with history of congestive heart failure and NYHA Class III-IV symptoms at any time. Patients for whom living donor renal transplantation is already scheduled or in the process of being evaluated, as these patients will be unlikely to complete study protocols before transplantation. Patients with severe co-morbid conditions (eg, symptomatic hepatic cirrhosis, metastatic cancer, HIV infection with AIDS). Patient with active inflammatory process (eg., SLE, rheumatoid arthritis, gout) for which they are currently receiving immune modulating medications. Patients who are on corticosteroid therapy. Patients who do not consent to participate in the study.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dextromethorphan<br> | Drug: Dextromethorphan<br>* 60 mg, bid<br>|
| Active Comparator: Silymarin<br> | Drug: Silymarin<br>* 150 mg , tid<br>|
| Placebo Comparator: sugar pill<br> | Drug: sugar pill<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of eGFR | Use MDRD-simplified equation | 4 months | 
| Change of Urine TP/Cr |  | 4 months | 
| Change of serum hsCRP |  | 4 months | 
| Change of urine TGF-beta/Cr level | fibrotic marker of kidney | 4 months | 
| Endothelial function | by Flow-mediated dilatation mesured by Crdiovascular ultrasound | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Leukocyte ROCK activity | Measure leukocyte Ro kinase activity by western blotting This is an indicator of cardiovascular function | 4 months | 
| Blood MDA level | Indicator of oxidative stress | 4 months | 
| Blood TGF-beta | By Elisa | 4 months | 
| Urine MCP-1/Cr level |  | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CKD, proteinuria, dextromethorphan, silymarin, patients with 15 ml<eGFR< 60ml and 0.5 g/day<proteinuria<3g/day