Ignite Creation Date:
2024-10-26 @ 3:37 PM
Last Modification Date:
2024-10-26 @ 3:37 PM
Study NCT ID:
NCT06545461
Status:
COMPLETED
Last Update Posted:
None
First Post:
2024-08-05
Brief Title:
Treating Metabolic Acidosis in Chronic Kidney Disease to Prevent Adverse Kidney and Cardiovascular Outcomes
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Treating Metabolic Acidosis in Chronic Kidney Disease to Prevent Adverse Kidney and Cardiovascular Outcomes
Status:
COMPLETED
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Upon completion this project will determine if treatment of metabolic acidosis in non-diabetic study participants with reduced kidney function chronic kidney disease CKD stage 3 associated with high blood pressure hypertension and macroalbuminuria the latter indicating pronounced kidney injury using either base-producing fruits and vegetables FV or standard therapy for treatment of metabolic acidosis with the medication sodium bicarbonate NaHCO3 1 slows progression of CKD toward end-stage renal disease ESRD 2 improves indices of cardiovascular disease CVD risk and 3 better preserves plasma acid-base parameters These studies are designed to compare the differential effects of treating the metabolic acidosis of CKD with FVs or NaHCO3 on kidney outcomes including progression to ESRD on indices of CVD risk and on plasma acid-base parameters
Detailed Description:
The long-term objective of this study is to determine if treatment of metabolic acidosis in study participants with chronic kidney disease CKD reduced estimated glomerular filtration rate eGFR and very high levels of urine albumin excretion macroalbuminuria reduces risk for further eGFR decline andor for subsequent development of cardiovascular disease CVD The specific aims of this study are to determine if metabolic acidosis treatment with either base-producing fruits and vegetables FV in amounts calculated to reduce participant dietary acid content by half or sodium bicarbonate NaHCO3 03 mEqkg body weight an amount designed to match the alkali content of provided FV in participants with stage 3 CKD eGFR 30 to 59 mlmin173 m2 compared with Usual Care 1 slows CKD progression 2 improves indices of cardiovascular risk and 3 better preserves plasma acid-base parameters Despite blood pressure control with kidney protective drugs like angiotensin converting enzyme ACE inhibitors many patients with CKD and reduced eGFR have progressive eGFR decline toward end-stage renal disease ESRD with need for dialysis or kidney transplant to maintain life They also have increased risk to die of CVD Studies from our laboratory and those of other investigators support that treatment of metabolic acidosis slows GFR decline in animal models of CKD Many patients with CKD stage 3 have metabolic acidosis that might exacerbate eGFR decline and its treatment might slow or stop it This study will recruit participants with hypertension-associated CKD stage 3 eGFR 30-59 mlmin173 m2 without diabetes to avoid contribution of diabetes to eGFR decline They will have macroalbuminuria urine albumin mg-to-creatinine g ratio 200 mgg that increases their CKD progression risk to optimize the chance to see benefits of metabolic acidosis treatment They will have plasma total CO2 PTCO2 24 but 22 millimolar mM to recruit participants with metabolic acidosis that is not severe enough to warrant treatment by current guidelines with oral NaHCO3 to ethically randomize participants to received non-recommended treatment for metabolic acidosis FV or no treatment Usual Care Participants whose PTCO2 decreases to 22 mM or below during follow up will be treated with oral NaHCO3 tablets with the goal to maintain their PTCO2 22 mM All will undergo blood pressure control to target systolic blood pressure 130 mm Hg millimeters of mercury with regimens including ACE inhibition and will receive atorvastatin because their macroalbuminuria puts them at increase CVD risk At study entry and yearly for 10 years all participants will have 10 ml of blood drawn from an antecubital vein for measurement of the negative log of free hydrogen ion concentration pH partial pressure of carbon dioxide gas PCO2 PTCO2 creatinine LDL cholesterol HDL cholesterol Lpa cholesterol sodium potassium and chloride They will have 20 ml of urine collected for measurement of creatinine albumin N-acetyl-D-glucosaminidase angiotensinogen and isoprostane 8-isoprostaglandin F2 alpha They will also have an 8-hour urine collection at a Texas Tech University Health Sciences Center TTUHSC clinic at baseline 3 years 5 years and 10 years for PTCO2 pH ammonium titratable acidity creatinine sodium and potassium after fasting after midnight The course of plasma and urine parameters over the 10 years of follow up in those randomized to FV or NaHCO3 compared to Usual Care will help determine the effects treatment of metabolic acidosis on CKD progression change in urine indices of kidney injury and eGFR indices of CVD risk change in LDL HDL and Lpa cholesterol and on participant acid-base status serum acid-base parameters pH PCO2 bicarbonate concentration HCO3 and PTCO2 These studies will also determine differences in metabolic acidosis treatment with FV vs NaHCO3 We hypothesize that metabolic acidosis treatment with FV or NaHCO3 will 1 slow CKD progression indicated by lower urine kidney injury indices and slower eGFR decline 2 improve indices of cardiovascular risk indicated by lower LDL lower Lpa and higher HDL cholesterol and 3 improve plasma acid-base status indicated by higher PTCO2 Excretion of urine acid-base parameters will help determine effects of these treatments on urine acid excretion Blood pH and PCO2 will be measured using the Immediate Response Mobile Analysis IRMA blood analysis system and blood and urine concentrations of albumin and creatinine will be measured with standard techniques Blood and urine PTCO2 will be measured as done previously with fluorimetry in the PIs laboratory Urine ammonium titratable acidity N-Acetyl-beta-D-glucosaminidase angiotensinogen and isoprostane 8-isoprostaglandin F2 alpha will be measured as done previously in the laboratory of the Co-PI
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None