Abstract: SA-PO912
Nitrite, Isoquercetin, and Endothelial Dysfunction Trial (NICE trial): Design and Preliminary Data
Session Information
- CKD: Clinical, Outcomes, Trials - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Chen, Jing, Tulane School of Medicine, New Orleans, Louisiana, United States
- Hamm, L. Lee, Tulane University School of Medicine, New Orleans, Louisiana, United States
- Bundy, Joshua David, Northwestern University Feinberg School of Medicine, Evanston, Illinois, United States
- Kumbala, Damodar R., Renal Associates of Baton Rouge, LLC, Metairie, Louisiana, United States
- Bodana, Shirisha, Ochsner Clinc Foundation, Metairie, Louisiana, United States
- Chen, Chung-shiuan, Tulane University, New Orleans, Louisiana, United States
- Starcke, Charlton Claire, Tulane University, New Orleans, Louisiana, United States
- Mahone, Erin, Tulane University, New Orleans, Louisiana, United States
- Vadalia, Aarti, Tulane University, New Orleans, Louisiana, United States
- Obst, Katherine Meredith, Tulane University, New Orleans, Louisiana, United States
- Bokhari, Syed Rizwan A., Tulane School of Medicine, New Orleans, Louisiana, United States
- Alper, Arnold B., Tulane University Helath Science Center, New Orleans, Louisiana, United States
- Lukitsch, Ivo, Ochsner Healt Center, New Orleans, Louisiana, United States
- Kleinpeter, Myra A., Tulane University School of Medicine, New Orleans, Louisiana, United States
- He, Hua, School of Public Health and Tropic MedicineTulane University, New Orleans, Louisiana, United States
- He, Jiang, Tulane School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States
Background
Endothelial dysfunction may be an early etiology for chronic kidney disease (CKD) and cardiovascular disease in CKD. We studied the safety and efficacy of combination treatment with sodium nitrite and isoqercetin on endothelial dysfunction, inflammation and oxidative stress in CKD patients.
Methods
This double blind, randomized, placebo-controlled trial enrolled 70 CKD patients. 35 patients were randomly assigned to oral combination of immediate-release sodium nitrite (40 mg twice daily) and isoquercetin (225 mg, once daily) or placebo for 3 months. The primary endpoint was changes in flow-mediated dilation (FMD) from baseline. The secondary endpoints were changes in biomarkers of endothelial function, inflammation, oxidative stress, eGFR, and urine albumin.The follow-up rate was 97%. Mixed-effects models were used to assess the treatment effects.
Results
Baseline characteristics were similar between groups. FMD increased by 1.13% (95% confidence interval [CI], -0.07 to 2.32) vs. 0.34% (95% CI, -0.86 to 1.53) in treatment vs. placebo group (p=0.35). The level of von Willebrand factor (vWF) decreased by 695 pg/mL (95% CI, -3793 to 2403) vs. increased by 2768 pg/mL (95% CI, -300 to 5838) in treatment vs. placebo group (p=0.047). There were statistically insignificant reductions between treatment and placebo groups in other biomarkers of endothelial dysfunction (intercellular adhesion molecule-1, vascular adhesion molecule-1, E-selectin, and Endothelin-1), oxidative stress (oxidized low-density lipoprotein and nitrotyrosine), and urine albumin. Additionally, there were no differences in changes of inflammatory biomarkers (C-reactive protein, tumor necrosis factor-α, interleukin [IL]-6, and monocyte chemoattractant protein-1) except IL-17 (1.35 [95% CI, 0.87 to 1.82] vs. 1.98 [95% CI, 1.50 to 2.45] in treatment vs. placebo group, p=0.05). There was no significant change in eGFR between groups. Methemoglobin and side effects were not different between groups.
Conclusion
The combination treatment significantly reduces vWF and IL-17 and may potentially improve endothelial dysfunction, inflammation, oxidative stress, and proteinuria. Larger trial is warranted to confirm those findings.
Funding
- Other NIH Support