Effect of Urinary Alkalinization on Urine Uric Acid Precipitation and Crystallization in Adults With Type 1 Diabetes

NCT02502071 | Completed Phase 4 Results DMC

• 1 other identifier: 15-0541
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 1 Diabetes; Diabetic Nephropathy; Diabetic Kidney Disease

Outcome Measures

Primary Outcomes (2)

• Change in Urine Uric Acid Concentration (Increased Solubility) by Assay

  Urine uric acid were evaluated using a QuantiChrom UA kit assay (DIUA-250) with quantitative colorimetric UA determination at 590 nm (BioAssay System, California, USA).

  Day 1 (pre-therapy) and Day 2 (post-therapy)

• Change in Number of Participants With Urine Uric Acid Precipitation by Polarized Microscopy

  Urine uric acid crystals were identified by polarized microscopy (Polarized light imaging Zeiss Axiovert 135; 0.3NA objective), and pictures were captured from each urine sample. UA crystals were defined dichotomously as being present or absent.

  Day 1 (pre-therapy) and Day 2 (post-therapy)

Study Arms (1)

Sodium Bicarbonate

EXPERIMENTAL

All participants will receive 2 doses of 1950mg Sodium Bicarbonate

Drug: sodium bicarbonate

Interventions

sodium bicarbonate DRUG

All participants will receive 2 doses of 1950mg sodium bicarbonate

Also known as: NaHCO3

Sodium Bicarbonate

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adults (aged 18-45 years) with type 1 diabetes
• Participants must be able to be fasting prior to study visit and give informed consent.

You may not qualify if:

• Non-type 1 diabetes
• History of eGFR \<60 ml/min/1.73m2 or microalbuminuria or greater
• History of hypocalcemia or at risk of hypocalcemia
• Taking allopurinol or uric acid altering medications
• Ketogenic diet
• Ketonuria
• Taking phosphorus binders (e.g. sevelamer)
• Pregnant or breastfeeding
• Taking the following medications which may interact with sodium bicarbonate (e.g. phentermine, pseudoephedrine, antifungal medication, cephalosporin antibiotics \[e.g. Keflex\], tetracycline antibiotics \[e.g. doxycycline\], steroids or lithium)
• Taking SGLT-2 inhibitors
• Taking blood pressure medications

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

Barbara Davis Center for Diabetes

Aurora, Colorado, 80045, United States

Location

Related Publications (12)

• Drummond K, Mauer M; International Diabetic Nephropathy Study Group. The early natural history of nephropathy in type 1 diabetes: II. Early renal structural changes in type 1 diabetes. Diabetes. 2002 May;51(5):1580-7. doi: 10.2337/diabetes.51.5.1580.

  PMID: 11978659 BACKGROUND

• Gilbert RE, Cooper ME. The tubulointerstitium in progressive diabetic kidney disease: more than an aftermath of glomerular injury? Kidney Int. 1999 Nov;56(5):1627-37. doi: 10.1046/j.1523-1755.1999.00721.x.

  PMID: 10571771 BACKGROUND

• Ginevri F, Piccotti E, Alinovi R, DeToni T, Biagini C, Chiggeri GM, Gusmano R. Reversible tubular proteinuria precedes microalbuminuria and correlates with the metabolic status in diabetic children. Pediatr Nephrol. 1993 Feb;7(1):23-6. doi: 10.1007/BF00861555.

  PMID: 8439475 BACKGROUND

• Bjornstad P, Snell-Bergeon JK, McFann K, Wadwa RP, Rewers M, Rivard CJ, Jalal D, Chonchol MB, Johnson RJ, Maahs DM. Serum uric acid and insulin sensitivity in adolescents and adults with and without type 1 diabetes. J Diabetes Complications. 2014 May-Jun;28(3):298-304. doi: 10.1016/j.jdiacomp.2013.12.007. Epub 2013 Dec 27.

  PMID: 24461546 BACKGROUND

• Bjornstad P, Lanaspa MA, Ishimoto T, Kosugi T, Kume S, Jalal D, Maahs DM, Snell-Bergeon JK, Johnson RJ, Nakagawa T. Fructose and uric acid in diabetic nephropathy. Diabetologia. 2015 Sep;58(9):1993-2002. doi: 10.1007/s00125-015-3650-4. Epub 2015 Jun 7.

  PMID: 26049401 BACKGROUND

• Bjornstad P, Maahs DM, Rivard CJ, Pyle L, Rewers M, Johnson RJ, Snell-Bergeon JK. Serum uric acid predicts vascular complications in adults with type 1 diabetes: the coronary artery calcification in type 1 diabetes study. Acta Diabetol. 2014 Oct;51(5):783-91. doi: 10.1007/s00592-014-0611-1. Epub 2014 Jun 15.

  PMID: 24929955 BACKGROUND

• Maahs DM, Caramori L, Cherney DZ, Galecki AT, Gao C, Jalal D, Perkins BA, Pop-Busui R, Rossing P, Mauer M, Doria A; PERL Consortium. Uric acid lowering to prevent kidney function loss in diabetes: the preventing early renal function loss (PERL) allopurinol study. Curr Diab Rep. 2013 Aug;13(4):550-9. doi: 10.1007/s11892-013-0381-0.

  PMID: 23649945 BACKGROUND

• Lytvyn Y, Skrtic M, Yang GK, Yip PM, Perkins BA, Cherney DZ. Glycosuria-mediated urinary uric acid excretion in patients with uncomplicated type 1 diabetes mellitus. Am J Physiol Renal Physiol. 2015 Jan 15;308(2):F77-83. doi: 10.1152/ajprenal.00555.2014. Epub 2014 Nov 5.

  PMID: 25377916 BACKGROUND

• Schepers MS, van Ballegooijen ES, Bangma CH, Verkoelen CF. Crystals cause acute necrotic cell death in renal proximal tubule cells, but not in collecting tubule cells. Kidney Int. 2005 Oct;68(4):1543-53. doi: 10.1111/j.1523-1755.2005.00566.x.

  PMID: 16164631 BACKGROUND

• Ryu ES, Kim MJ, Shin HS, Jang YH, Choi HS, Jo I, Johnson RJ, Kang DH. Uric acid-induced phenotypic transition of renal tubular cells as a novel mechanism of chronic kidney disease. Am J Physiol Renal Physiol. 2013 Mar 1;304(5):F471-80. doi: 10.1152/ajprenal.00560.2012. Epub 2013 Jan 2.

  PMID: 23283992 BACKGROUND

• Verzola D, Ratto E, Villaggio B, Parodi EL, Pontremoli R, Garibotto G, Viazzi F. Uric acid promotes apoptosis in human proximal tubule cells by oxidative stress and the activation of NADPH oxidase NOX 4. PLoS One. 2014 Dec 16;9(12):e115210. doi: 10.1371/journal.pone.0115210. eCollection 2014.

  PMID: 25514209 BACKGROUND

• Cohen B, Laish I, Brosh-Nissimov T, Hoffman A, Katz LH, Braunstein R, Sagi R, Michael G. Efficacy of urine alkalinization by oral administration of sodium bicarbonate: a prospective open-label trial. Am J Emerg Med. 2013 Dec;31(12):1703-6. doi: 10.1016/j.ajem.2013.08.031. Epub 2013 Sep 20.

  PMID: 24055481 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetic Nephropathies

Interventions

Sodium Bicarbonate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications

Intervention Hierarchy (Ancestors)

Bicarbonates; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Dr. Petter Bjornstad, Assistant Professor
• Organization: University of Colorado School of Medicine

petter.bjornstad@childrenscolorado.org

7207774659

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2015
• First Posted: July 20, 2015
• Study Start: January 1, 2017
• Primary Completion: July 1, 2017
• Study Completion: August 1, 2017
• Last Updated: January 24, 2022
• Results First Posted: November 20, 2018

Record last verified: 2022-01

Locations

US (1)