Ignite Creation Date:
2024-05-06 @ 7:17 AM
Last Modification Date:
2024-10-26 @ 11:46 AM
Study NCT ID:
NCT02502071
Status:
COMPLETED
Last Update Posted:
2022-01-24
First Post:
2015-07-16
Brief Title:
Effect of Urinary Alkalinization on Urine Uric Acid Precipitation and Crystallization in Adults With Type 1 Diabetes
Sponsor:
University of Colorado Denver
Organization:
University of Colorado Denver
Study Overview
Official Title:
Effect of Urinary Alkalinization on Urine Uric Acid Precipitation and Crystallization in Adults With Type 1 DiabetesL a Open-label Trial
Status:
COMPLETED
Status Verified Date:
2022-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Alk-UA
Brief Summary:
The purpose of this study is to determine whether alkalinization of urine uric acid by 2 doses of sodium bicarbonate 1950mg over 24-hours reduces precipitation and crystallization of urine uric acid over in adults with type 1 diabetes
Detailed Description:
Diabetic nephropathy is characterized not only by glomerular disease but also tubulointerstitial injury The tubular changes associated with diabetic nephropathy include basement membrane thickening tubular hypertrophy epithelial-mesenchymal transition glycogen accumulation and interstitial inflammation Although glomerular changes has received significantly more attention from researchers and clinicians than tubulointerstitial changes in diabetes tubular injury is known to associate better with renal function than glomerular injury In fact tubular proteinuria may precede microalbuminuria with type 1 diabetes suggesting that tubular damage may be induced earlier than glomerular injury in the course of diabetic nephropathy
Serum uric acid SUA is lower in adolescents and adults with type 1 diabetes compared to non-diabetic peers Despite lower levels SUA remains an important risk factor for diabetic nephropathy in type 1 diabetes with a large clinical trial underway examining the ability of allopurinol to prevent early renal loss Several mechanisms have been proposed to explain the lower levels of SUA in type 1 diabetes including glucosuria induced uricosuria leading to spilling of urine uric acid UUA and lowering of SUA and the notion that intracellular uric acid IUA and or UUA rather than SUA may be responsible for the development of complications Animal studies have demonstrated that blocking uric acid production protects the kidney from tubulointerstitial injury which suggests a causal role for uric acid in the development of diabetic tubular injury Relative dehydration secondary to glucosuria exercise or inadequate liquid intake may lead to concentrated and acidic urine which may cause UUA to precipitate and crystallize in type 1 diabetes The UUA precipitation and crystallization is thought to induce inflammation and injury of the tubules with possible retrograde glomerular injury Moreover it was recently shown that UUA promoted apoptosis in human proximal tubular cells by oxidative stress and activation of NADPH Oxidase NOX 4
Oral alkali replacements are readily available safe and include the following formulations sodium bicarbonate BiCitra sodium citrate and citric acid PolyCitra citric acid sodium citrate and potassium citrate polycitra-K potassium citrate and citric acid In contrast to sodium bicarbonate citrate is converted to bicarbonate in the liver and thus this conversion is affected by liver disease Usual adult doses for urinary alkalinization are 325 to 2000 mg orally 1 to 4 times a day One gram provides 12 mEq mmoL each of sodium and bicarbonate and is titrated to a goal of urine pH of 80 In a prospective open-label trial 4 g of sodium bicarbonate was administered orally 3 times daily to 9 healthy volunteers for 24 hours and after 10 hours all participants had a urine pH 7 and after 20 hours all participants had urine pH 8 No adverse effects or abnormal blood results were documented during the 24-hour follow-up Urinary alkalinization should solubilize UUA thereby increasing the concentration of uric acid in urine and decreasing precipitation and crystallization of UUA It is unknown whether alkalinization of urine reduces UUA precipitation and crystallization in type 1 diabetes
With diabetic nephropathy being the leading cause of end-stage renal disease in the Western world it is critical to develop a better understanding of the determinants of risk and progression of early diabetic nephropathy to improve outcomes in patients with type 1 diabetes UUA is a particularly attractive therapeutic target due to the potential to reduce tubular injury with sodium bicarbonate Accordingly the investigators propose a pilot experimental study examining the effect of urine alkalinization with oral sodium bicarbonate on UUA precipitation and crystallization in adults with type 1 diabetes
Serum uric acid SUA is lower in adolescents and adults with type 1 diabetes compared to non-diabetic peers Despite lower levels SUA remains an important risk factor for diabetic nephropathy in type 1 diabetes with a large clinical trial underway examining the ability of allopurinol to prevent early renal loss Several mechanisms have been proposed to explain the lower levels of SUA in type 1 diabetes including glucosuria induced uricosuria leading to spilling of urine uric acid UUA and lowering of SUA and the notion that intracellular uric acid IUA and or UUA rather than SUA may be responsible for the development of complications Animal studies have demonstrated that blocking uric acid production protects the kidney from tubulointerstitial injury which suggests a causal role for uric acid in the development of diabetic tubular injury Relative dehydration secondary to glucosuria exercise or inadequate liquid intake may lead to concentrated and acidic urine which may cause UUA to precipitate and crystallize in type 1 diabetes The UUA precipitation and crystallization is thought to induce inflammation and injury of the tubules with possible retrograde glomerular injury Moreover it was recently shown that UUA promoted apoptosis in human proximal tubular cells by oxidative stress and activation of NADPH Oxidase NOX 4
Oral alkali replacements are readily available safe and include the following formulations sodium bicarbonate BiCitra sodium citrate and citric acid PolyCitra citric acid sodium citrate and potassium citrate polycitra-K potassium citrate and citric acid In contrast to sodium bicarbonate citrate is converted to bicarbonate in the liver and thus this conversion is affected by liver disease Usual adult doses for urinary alkalinization are 325 to 2000 mg orally 1 to 4 times a day One gram provides 12 mEq mmoL each of sodium and bicarbonate and is titrated to a goal of urine pH of 80 In a prospective open-label trial 4 g of sodium bicarbonate was administered orally 3 times daily to 9 healthy volunteers for 24 hours and after 10 hours all participants had a urine pH 7 and after 20 hours all participants had urine pH 8 No adverse effects or abnormal blood results were documented during the 24-hour follow-up Urinary alkalinization should solubilize UUA thereby increasing the concentration of uric acid in urine and decreasing precipitation and crystallization of UUA It is unknown whether alkalinization of urine reduces UUA precipitation and crystallization in type 1 diabetes
With diabetic nephropathy being the leading cause of end-stage renal disease in the Western world it is critical to develop a better understanding of the determinants of risk and progression of early diabetic nephropathy to improve outcomes in patients with type 1 diabetes UUA is a particularly attractive therapeutic target due to the potential to reduce tubular injury with sodium bicarbonate Accordingly the investigators propose a pilot experimental study examining the effect of urine alkalinization with oral sodium bicarbonate on UUA precipitation and crystallization in adults with type 1 diabetes
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