NCT04073719

Brief 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.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
50

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Sep 2019

Typical duration for not_applicable

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 28, 2019

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 29, 2019

Completed
3 days until next milestone

Study Start

First participant enrolled

September 1, 2019

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 31, 2021

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

May 31, 2022

Completed
Last Updated

August 30, 2019

Status Verified

August 1, 2019

Enrollment Period

1.7 years

First QC Date

August 28, 2019

Last Update Submit

August 28, 2019

Conditions

Kidney Stones, Urolithiasis, Hypocitraturia

Keywords

Kidney Stones, Urolithiasis, Hypocitraturia, Apple Cider Vinegar

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (3)

  • Apple Cider Vinegar and urinary pH

    1 week

  • Apple Cider Vinegar Against Other Beverages

    4 weeks

  • Palatability Evaluation

    4 weeks

Study Arms (12)

Apple Cider Vinegar + Coconut Water

EXPERIMENTAL

Patients will drink apple cider vinegar for 7 days. After a washout period of 2 weeks, patients will then drink coconut water for 7 days.

Dietary Supplement: Apple Cider Vinegar

Apple Cider Vinegar + Citric Soda

EXPERIMENTAL

Patients will drink apple cider vinegar for 7 days. After a washout period of 2 weeks, patients will then drink citric soda for 7 days.

Dietary Supplement: Apple Cider Vinegar

Apple Cider Vinegar + Lemonade

EXPERIMENTAL

Patients will drink apple cider vinegar for 7 days. After a washout period of 2 weeks, patients will then drink lemonade for 7 days.

Dietary Supplement: Apple Cider Vinegar

Coconut Water + Apple Cider Vinegar

EXPERIMENTAL

Patients will drink coconut water for 7 days. After a washout period of 2 weeks, patients will then drink apple cider vinegar for 7 days.

Dietary Supplement: Apple Cider Vinegar

Coconut Water + Citric Soda

EXPERIMENTAL

Patients will drink coconut water for 7 days. After a washout period of 2 weeks, patients will then drink citric soda for 7 days.

Dietary Supplement: Other Beverage

Coconut Water + Lemonade

EXPERIMENTAL

Patients will drink coconut water for 7 days. After a washout period of 2 weeks, patients will then drink lemonade for 7 days.

Dietary Supplement: Other Beverage

Citric Soda + Apple Cider Vinegar

EXPERIMENTAL

Patients will drink citric soda for 7 days. After a washout period of 2 weeks, patients will then drink apple cider vinegar for 7 days.

Dietary Supplement: Apple Cider VinegarDietary Supplement: Other Beverage

Citric Soda + Coconut Water

EXPERIMENTAL

Patients will drink citric soda for 7 days. After a washout period of 2 weeks, patients will then drink coconut water for 7 days.

Dietary Supplement: Other Beverage

Citric Soda + Lemonade

EXPERIMENTAL

Patients will drink citric soda for 7 days. After a washout period of 2 weeks, patients will then drink lemonade for 7 days.

Dietary Supplement: Other Beverage

Lemonade + Apple Cider Vinegar

EXPERIMENTAL

Patients will drink lemonade for 7 days. After a washout period of 2 weeks, patients will then drink apple cider vinegar for 7 days.

Dietary Supplement: Apple Cider Vinegar

Lemonade + Coconut Water

EXPERIMENTAL

Patients will drink lemonade for 7 days. After a washout period of 2 weeks, patients will then drink coconut water for 7 days.

Dietary Supplement: Other Beverage

Lemonade + Citric Soda

EXPERIMENTAL

Patients will drink lemonade for 7 days. After a washout period of 2 weeks, patients will then drink citric soda for 7 days.

Dietary Supplement: Other Beverage

Interventions

Apple Cider VinegarDIETARY_SUPPLEMENT

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.

Apple Cider Vinegar + Citric SodaApple Cider Vinegar + Coconut WaterApple Cider Vinegar + LemonadeCitric Soda + Apple Cider VinegarCoconut Water + Apple Cider VinegarLemonade + Apple Cider Vinegar
Other BeverageDIETARY_SUPPLEMENT

To what degree do other high citrate beverages impact urinary citrate output.

Citric Soda + Apple Cider VinegarCitric Soda + Coconut WaterCitric Soda + LemonadeCoconut Water + Citric SodaCoconut Water + LemonadeLemonade + Citric SodaLemonade + Coconut Water

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male and female volunteers 18-65 years old

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (43)

  • 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.

    PMID: 22498635BACKGROUND

  • 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. doi: 10.1097/01.ju.0000152082.14384.d7.

    PMID: 15711292BACKGROUND

  • 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. doi: 10.1038/ki.1979.173.

    PMID: 548606BACKGROUND

  • Bansal AD, Hui J, Goldfarb DS. Asymptomatic nephrolithiasis detected by ultrasound. Clin J Am Soc Nephrol. 2009 Mar;4(3):680-4. doi: 10.2215/CJN.05181008. Epub 2009 Mar 4.

    PMID: 19261817BACKGROUND

  • 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.

    PMID: 27847289BACKGROUND

  • 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.

    PMID: 20096421BACKGROUND

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

    PMID: 18408483BACKGROUND

  • 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.

    PMID: 21124301BACKGROUND

  • 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.

    PMID: 19078968BACKGROUND

  • Worcester EM, Coe FL. Clinical practice. Calcium kidney stones. N Engl J Med. 2010 Sep 2;363(10):954-63. doi: 10.1056/NEJMcp1001011. No abstract available.

    PMID: 20818905BACKGROUND

  • Curhan GC, Taylor EN. 24-h uric acid excretion and the risk of kidney stones. Kidney Int. 2008 Feb;73(4):489-96. doi: 10.1038/sj.ki.5002708. Epub 2007 Dec 5.

    PMID: 18059457BACKGROUND

  • Nicar MJ, Skurla C, Sakhaee K, Pak CY. Low urinary citrate excretion in nephrolithiasis. Urology. 1983 Jan;21(1):8-14. doi: 10.1016/0090-4295(83)90113-9.

    PMID: 6823713BACKGROUND

  • 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. doi: 10.1210/jcem-55-6-1052.

    PMID: 7130336BACKGROUND

  • 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. doi: 10.1016/s0002-9343(03)00201-8.

    PMID: 12867231BACKGROUND

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

    PMID: 7783699BACKGROUND

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

    PMID: 19918339BACKGROUND

  • Ryall RL. Urinary inhibitors of calcium oxalate crystallization and their potential role in stone formation. World J Urol. 1997;15(3):155-64. doi: 10.1007/BF02201852. No abstract available.

    PMID: 9228722BACKGROUND

  • Sheng X, Jung T, Wesson JA, Ward MD. Adhesion at calcium oxalate crystal surfaces and the effect of urinary constituents. Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):267-72. doi: 10.1073/pnas.0406835101. Epub 2004 Dec 29.

    PMID: 15625112BACKGROUND

  • 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. doi: 10.1016/s0140-6736(86)91329-2.

    PMID: 2871335BACKGROUND

  • 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. doi: 10.1016/s0022-5347(17)46963-1.

    PMID: 4009822BACKGROUND

  • 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. doi: 10.1016/s0022-5347(17)46962-x.

    PMID: 3892044BACKGROUND

  • Pak CY, Sakhaee K, Fuller C. Successful management of uric acid nephrolithiasis with potassium citrate. Kidney Int. 1986 Sep;30(3):422-8. doi: 10.1038/ki.1986.201.

    PMID: 3784284BACKGROUND

  • 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. doi: 10.1016/s0022-5347(17)35888-3.

    PMID: 8230497BACKGROUND

  • 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. doi: 10.1016/s0022-5347(01)68155-2.

    PMID: 9366314BACKGROUND

  • Soygur T, Akbay A, Kupeli 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. doi: 10.1089/089277902753716098.

    PMID: 12028622BACKGROUND

  • 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. doi: 10.1016/j.juro.2007.01.061.

    PMID: 17437820BACKGROUND

  • Mattle D, Hess B. Preventive treatment of nephrolithiasis with alkali citrate--a critical review. Urol Res. 2005 May;33(2):73-9. doi: 10.1007/s00240-005-0464-8. Epub 2005 May 4.

    PMID: 15875173BACKGROUND

  • 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. doi: 10.1016/j.urology.2007.02.008.

    PMID: 17572176BACKGROUND

  • Seltzer MA, Low RK, McDonald M, Shami GS, Stoller ML. Dietary manipulation with lemonade to treat hypocitraturic calcium nephrolithiasis. J Urol. 1996 Sep;156(3):907-9.

    PMID: 8709360BACKGROUND

  • 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. doi: 10.1016/j.juro.2006.11.058.

    PMID: 17382731BACKGROUND

  • 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. doi: 10.1016/j.urology.2007.06.1115. Epub 2007 Oct 24.

    PMID: 17919696BACKGROUND

  • 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. doi: 10.2215/CJN.00800306. Epub 2006 Aug 30.

    PMID: 17699358BACKGROUND

  • 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.

    PMID: 18290732BACKGROUND

  • 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.

    PMID: 18578663BACKGROUND

  • 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.

    PMID: 30515390BACKGROUND

  • 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.

    PMID: 26176799BACKGROUND

  • 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. doi: 10.1271/bbb.60668. Epub 2007 May 7.

    PMID: 17485860BACKGROUND

  • 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. doi: 10.1271/bbb.90231. Epub 2009 Aug 7.

    PMID: 19661687BACKGROUND

  • 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.

    PMID: 7796781BACKGROUND

  • 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. doi: 10.2337/dc07-1062. Epub 2007 Aug 21. No abstract available.

    PMID: 17712024BACKGROUND

  • 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. doi: 10.2337/diacare.27.1.281. No abstract available.

    PMID: 14694010BACKGROUND

  • 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. doi: 10.3923/pjbs.2008.2634.2638.

    PMID: 19630216BACKGROUND

  • Baker B, Herforth C, Low J, Craig R, Christman M. Apple cider vinegar for prevention of urinary lithiasis (APUL): a randomized crossover trial. Int Urol Nephrol. 2025 Dec 6. doi: 10.1007/s11255-025-04944-x. Online ahead of print.

    PMID: 41351751DERIVED

MeSH Terms

Conditions

Kidney CalculiUrolithiasis

Condition Hierarchy (Ancestors)

NephrolithiasisKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesUrinary CalculiMale Urogenital DiseasesCalculiPathological Conditions, AnatomicalPathological Conditions, Signs and Symptoms

Central Study Contacts

Christine M Herfroth, MD

CONTACT

6195327227christine.m.herforth.mil@mail.mil

Jesse E Resovsky, BS

CONTACT

6195327226jreso001@gmail.com

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Model Details: Prospective randomized sample of 36 patients, in a nested cross over design.
Sponsor Type
FED
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Urology Resident

Study Record Dates

First Submitted

August 28, 2019

First Posted

August 29, 2019

Study Start

September 1, 2019

Primary Completion

May 31, 2021

Study Completion

May 31, 2022

Last Updated

August 30, 2019

Record last verified: 2019-08

Data Sharing

IPD Sharing
Will not share