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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT04073719
Other study ID # NMCSD.2019.0026
Secondary ID
Status Not yet recruiting
Phase N/A
First received
Last updated
Start date September 1, 2019
Est. completion date May 31, 2022

Study information

Verified date August 2019
Source United States Naval Medical Center, San Diego
Contact Christine M Herfroth, MD
Phone 6195327227
Email christine.m.herforth.mil@mail.mil
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to assess whether certain beverages can increase urinary citrate levels in healthy individuals with no history of kidney disease.


Description:

Higher urinary citrate levels have been shown to decrease one's risk of developing kidney stones. The study will compare apple cider vinegar, coconut water, diet citric soda and lemonade and determine which is superior at raising citrate levels. Research participants will consume two of the four drinks, each for 7 day periods, according to a prescribed regimen. Throughout the course of the study, participants will periodically provide blood draws for metabolic panels, as well as 24-hour urine samples to measure citrate levels. There will be 12 study arms, accounting for the permutations of two drinks for each patients out of four possibilities. 3 participants per arm is the goal, for a total of 36, but the recruitment aim is 50 participants, to account for dropout and noncompliance.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 50
Est. completion date May 31, 2022
Est. primary completion date May 31, 2021
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 65 Years
Eligibility Inclusion Criteria:

- Male and female volunteers 18-65 years old

Exclusion Criteria:

- History of peptic ulcer disease or gastroparesis

- Pregnant females

- History of chronic kidney disease

- History of urolithiasis

- Currently taking medications that interfere with urinary electrolyte excretion (thiazide and loop diuretics)javascript:document.

- History of Diabetes

Study Design


Related Conditions & MeSH terms


Intervention

Dietary Supplement:
Apple Cider Vinegar
Will drinking apple cider vinegar increase urinary citrate levels to a greater degree than other beverages and which beverages produce the most significant effects compared against one another.
Other Beverage
To what degree do other high citrate beverages impact urinary citrate output.

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
United States Naval Medical Center, San Diego

References & Publications (42)

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Barcelo P, Wuhl O, Servitge E, Rousaud A, Pak CY. Randomized double-blind study of potassium citrate in idiopathic hypocitraturic calcium nephrolithiasis. J Urol. 1993 Dec;150(6):1761-4. — View Citation

Bhatti UH, Duffy AJ, Roberts KE, Shariff AH. Nephrolithiasis after bariatric surgery: A review of pathophysiologic mechanisms and procedural risk. Int J Surg. 2016 Dec;36(Pt D):618-623. doi: 10.1016/j.ijsu.2016.11.025. Epub 2016 Nov 12. Review. — View Citation

Brighenti F, Castellani G, Benini L, Casiraghi MC, Leopardi E, Crovetti R, Testolin G. Effect of neutralized and native vinegar on blood glucose and acetate responses to a mixed meal in healthy subjects. Eur J Clin Nutr. 1995 Apr;49(4):242-7. — View Citation

Curhan GC, Taylor EN. 24-h uric acid excretion and the risk of kidney stones. Kidney Int. 2008 Feb;73(4):489-96. Epub 2007 Dec 5. — View Citation

Ettinger B, Pak CY, Citron JT, Thomas C, Adams-Huet B, Vangessel A. Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis. J Urol. 1997 Dec;158(6):2069-73. — View Citation

Haleblian GE, Leitao VA, Pierre SA, Robinson MR, Albala DM, Ribeiro AA, Preminger GM. Assessment of citrate concentrations in citrus fruit-based juices and beverages: implications for management of hypocitraturic nephrolithiasis. J Endourol. 2008 Jun;22(6):1359-66. doi: 10.1089/end.2008.0069. — View Citation

Johnson CM, Wilson DM, O'Fallon WM, Malek RS, Kurland LT. Renal stone epidemiology: a 25-year study in Rochester, Minnesota. Kidney Int. 1979 Nov;16(5):624-31. — View Citation

Johnston CS, Kim CM, Buller AJ. Vinegar improves insulin sensitivity to a high-carbohydrate meal in subjects with insulin resistance or type 2 diabetes. Diabetes Care. 2004 Jan;27(1):281-2. — View Citation

Kang DE, Maloney MM, Haleblian GE, Springhart WP, Honeycutt EF, Eisenstein EL, Marguet CG, Preminger GM. Effect of medical management on recurrent stone formation following percutaneous nephrolithotomy. J Urol. 2007 May;177(5):1785-8; discussion 1788-9. — View Citation

Kang DE, Sur RL, Haleblian GE, Fitzsimons NJ, Borawski KM, Preminger GM. Long-term lemonade based dietary manipulation in patients with hypocitraturic nephrolithiasis. J Urol. 2007 Apr;177(4):1358-62; discussion 1362; quiz 1591. — View Citation

Koff SG, Paquette EL, Cullen J, Gancarczyk KK, Tucciarone PR, Schenkman NS. Comparison between lemonade and potassium citrate and impact on urine pH and 24-hour urine parameters in patients with kidney stone formation. Urology. 2007 Jun;69(6):1013-6. — View Citation

Kok DJ, Papapoulos SE, Bijvoet OL. Excessive crystal agglomeration with low citrate excretion in recurrent stone-formers. Lancet. 1986 May 10;1(8489):1056-8. — View Citation

Kondo T, Kishi M, Fushimi T, Ugajin S, Kaga T. Vinegar intake reduces body weight, body fat mass, and serum triglyceride levels in obese Japanese subjects. Biosci Biotechnol Biochem. 2009 Aug;73(8):1837-43. Epub 2009 Aug 7. — View Citation

Maalouf NM, Tondapu P, Guth ES, Livingston EH, Sakhaee K. Hypocitraturia and hyperoxaluria after Roux-en-Y gastric bypass surgery. J Urol. 2010 Mar;183(3):1026-30. doi: 10.1016/j.juro.2009.11.022. Epub 2010 Jan 21. — View Citation

Mattle D, Hess B. Preventive treatment of nephrolithiasis with alkali citrate--a critical review. Urol Res. 2005 May;33(2):73-9. Epub 2005 May 4. Review. — View Citation

Nicar MJ, Skurla C, Sakhaee K, Pak CY. Low urinary citrate excretion in nephrolithiasis. Urology. 1983 Jan;21(1):8-14. — View Citation

Odvina CV. Comparative value of orange juice versus lemonade in reducing stone-forming risk. Clin J Am Soc Nephrol. 2006 Nov;1(6):1269-74. Epub 2006 Aug 30. — View Citation

Pak CY, Fuller C, Sakhaee K, Preminger GM, Britton F. Long-term treatment of calcium nephrolithiasis with potassium citrate. J Urol. 1985 Jul;134(1):11-9. — View Citation

Pak CY, Poindexter JR, Adams-Huet B, Pearle MS. Predictive value of kidney stone composition in the detection of metabolic abnormalities. Am J Med. 2003 Jul;115(1):26-32. — View Citation

Pak CY, Sakhaee K, Fuller C. Successful management of uric acid nephrolithiasis with potassium citrate. Kidney Int. 1986 Sep;30(3):422-8. — View Citation

Pak CY. Citrate and renal calculi: an update. Miner Electrolyte Metab. 1994;20(6):371-7. Review. — View Citation

Patel RM, Jiang P, Asplin J, Granja I, Capretz T, Osann K, Okhunov Z, Landman J, Clayman RV. Coconut Water: An Unexpected Source of Urinary Citrate. Biomed Res Int. 2018 Nov 1;2018:3061742. doi: 10.1155/2018/3061742. eCollection 2018. — View Citation

Pearle MS, Calhoun EA, Curhan GC; Urologic Diseases of America Project. Urologic diseases in America project: urolithiasis. J Urol. 2005 Mar;173(3):848-57. — View Citation

Penniston KL, Nakada SY, Holmes RP, Assimos DG. Quantitative assessment of citric acid in lemon juice, lime juice, and commercially-available fruit juice products. J Endourol. 2008 Mar;22(3):567-70. doi: 10.1089/end.2007.0304. — View Citation

Penniston KL, Steele TH, Nakada SY. Lemonade therapy increases urinary citrate and urine volumes in patients with recurrent calcium oxalate stone formation. Urology. 2007 Nov;70(5):856-60. Epub 2007 Oct 24. — View Citation

Preminger GM, Sakhaee K, Skurla C, Pak CY. Prevention of recurrent calcium stone formation with potassium citrate therapy in patients with distal renal tubular acidosis. J Urol. 1985 Jul;134(1):20-3. — View Citation

Rudman D, Kutner MH, Redd SC 2nd, Waters WC 4th, Gerron GG, Bleier J. Hypocitraturia in calcium nephrolithiasis. J Clin Endocrinol Metab. 1982 Dec;55(6):1052-7. — View Citation

Ryall RL. Urinary inhibitors of calcium oxalate crystallization and their potential role in stone formation. World J Urol. 1997;15(3):155-64. Review. — View Citation

Sakhaee K, Maalouf NM, Kumar R, Pasch A, Moe OW. Nephrolithiasis-associated bone disease: pathogenesis and treatment options. Kidney Int. 2011 Feb;79(4):393-403. doi: 10.1038/ki.2010.473. Epub 2010 Dec 1. Review. — View Citation

Sakhaee K. Nephrolithiasis as a systemic disorder. Curr Opin Nephrol Hypertens. 2008 May;17(3):304-9. doi: 10.1097/MNH.0b013e3282f8b34d. Review. — View Citation

Sakhaee K. Recent advances in the pathophysiology of nephrolithiasis. Kidney Int. 2009 Mar;75(6):585-95. doi: 10.1038/ki.2008.626. Epub 2008 Dec 10. Review. — View Citation

Scales CD Jr, Smith AC, Hanley JM, Saigal CS; Urologic Diseases in America Project. Prevalence of kidney stones in the United States. Eur Urol. 2012 Jul;62(1):160-5. doi: 10.1016/j.eururo.2012.03.052. Epub 2012 Mar 31. — View Citation

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Shishehbor F, Mansoori A, Sarkaki AR, Jalali MT, Latifi SM. Apple cider vinegar attenuates lipid profile in normal and diabetic rats. Pak J Biol Sci. 2008 Dec 1;11(23):2634-8. — View Citation

Soygür T, Akbay A, Küpeli S. Effect of potassium citrate therapy on stone recurrence and residual fragments after shockwave lithotripsy in lower caliceal calcium oxalate urolithiasis: a randomized controlled trial. J Endourol. 2002 Apr;16(3):149-52. — View Citation

White AM, Johnston CS. Vinegar ingestion at bedtime moderates waking glucose concentrations in adults with well-controlled type 2 diabetes. Diabetes Care. 2007 Nov;30(11):2814-5. Epub 2007 Aug 21. — View Citation

Worcester EM, Coe FL. Clinical practice. Calcium kidney stones. N Engl J Med. 2010 Sep 2;363(10):954-63. doi: 10.1056/NEJMcp1001011. Review. — View Citation

Yamashita H, Fujisawa K, Ito E, Idei S, Kawaguchi N, Kimoto M, Hiemori M, Tsuji H. Improvement of obesity and glucose tolerance by acetate in Type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Biosci Biotechnol Biochem. 2007 May;71(5):1236-43. Epub 2007 May 7. — View Citation

Yamashita H. Biological Function of Acetic Acid-Improvement in Obesity and Glucose Tolerance by Acetic Acid in Type 2 Diabetic Rats. Crit Rev Food Sci Nutr. 2016 Jul 29;56 Suppl 1:S171-5. doi: 10.1080/10408398.2015.1045966. Review. — View Citation

Zuckerman JM, Assimos DG. Hypocitraturia: pathophysiology and medical management. Rev Urol. 2009 Summer;11(3):134-44. — View Citation

* Note: There are 42 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Apple Cider Vinegar Urinary Citrate Increase Determine the change in urinary citrate levels due to the addition of apple cider vinegar to the diet 1 week
Secondary Apple Cider Vinegar and urinary pH Determine the effect of apple cider vinegar on urinary pH 1 week
Secondary Apple Cider Vinegar Against Other Beverages Compare the effect of apple cider vinegar on urinary citrate with that of known citrate-rich beverages (lemonade, citrus based soda, coconut water) 4 weeks
Secondary Palatability Evaluation Compare the palatability of apple cider vinegar and other known citrate-rich beverages (lemonade, citrus based soda, coconut water). Patients will keep daily log whwere they can free write any side effects (from palatability perspective and otherwise). At the end of the study a 2 question survery (Likert scale format) will be filled in which participants will answer the liklihood of their willingness to consume the beverage daily for the prevention of kidney stones. 4 weeks