Prevention of Urinary Stones With Hydration

Not Applicable

Completed

• Conditions: Urinary Stones
• Interventions: Behavioral: Fluid prescription; Behavioral: Financial incentive; Behavioral: Structured Problem Solving

• Registration Number: NCT03244189
• Lead Sponsor: Duke University

Brief Summary

A randomized clinical trial to investigate the impact of increased fluid intake and increased urine output on the recurrence rate of urinary stone disease (USD) in adults and children. The primary aim of the trial is to determine whether a multi-component program of behavioral interventions to increase fluid intake will result in reduced risk of stone disease progression over a 2-year period.

Detailed Description

This is a two arm randomized controlled trial that incorporates pragmatic features, an adaptable intervention, patient choice, and remote monitoring of fluid intake through a "smart" water bottle. The study period is 24 months and will enroll approximately 1642 participants. Randomization will be stratified within a study site by age (adult vs. adolescent) and first time vs. recurrent stone former.

Intervention and control arm study participants will receive a smart water bottle that records daily fluid consumption, usual care including guideline-based recommendations of adequate fluid intake to decrease kidney stone recurrence, and periodic 24 hour urine collections, imaging (low-dose CT scan or ultrasound) and follow-up questionnaires.

Study Timeline

• Study First Submitted: 2017-08-02
• Study First Submitted QC: 2017-08-08
• Study First Posted: 2017-08-09
• Study Start: 2017-10-04
• Primary Completion: 2024-05-18
• Study Completion: 2024-05-31
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-05
• Last Update Posted: 2024-06-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1658

Inclusion Criteria

1. Aged ≥ 12 years

2. At least 1 symptomatic stone event (passage or procedural intervention) within 3 years prior to enrollment or a symptomatic stone event within 5 years if the patient also has new stone formation detected on imaging during the last 5 years. Symptomatic stone defined as any of the following:

   1. Stone passage
   2. Procedural intervention
   3. Radiographically or ultrasonographically confirmed stone with any of the following:

   i. Gross hematuria ii. Renal colic or atypical abdominal pain attributed to the stone, as determined by a treating provider iii. A clinical pattern of intermittent symptoms consistent with intermittent obstruction at the ureteropelvic junction, as determined by a treating provider

3. Low 24-hr urine volume

   1. ≥18 years old: <2.0 L/day
   2. <18 years old: <25 ml/Kg/day up to 2.0L/day

4. Able to provide informed consent (parental permission for children)

5. Owning and willing to use a smartphone or other device (e.g., tablet) compatible with the study-provided wireless enabled "smart" bottle

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Exclusion Criteria

1. Spinal cord injury

2. Currently undergoing active treatment for cancer except basal cell skin cancer, or patients with a history of cancer who completed their initial therapy <1 year before screening.

3. Known infectious (struvite), monogenic or other causes of stone disease for which therapies are likely to significantly alter course of stone disease

   1. Cystinuria
   2. Primary hyperoxaluria
   3. Primary xanthinuria
   4. Primary hyperparathyroidism
   5. Sarcoidosis
   6. Medullary sponge kidney

4. History or presence of hyponatremia (serum sodium <130 mmol/L) or hypo-osmolality (serum osmolality <275 mosm/kg)

5. Study participants with comorbidities that preclude high fluid intake or prior surgery precluding high fluid intake or leading to GI fluid losses

   1. History of or current Crohn's disease, ulcerative colitis, short gut syndrome (e.g. ileostomy, bowel bypass surgery to treat obesity, small bowel resection), chronic diarrhea, or GI tract ostomy.
   2. History of malabsorptive (e.g., Roux-en-Y gastric bypass) or restrictive (e.g., sleeve gastrectomy) bariatric surgery procedures
   3. Congestive heart failure

   i. NYHA class II or greater, and/or ii. Hospital admission in the past year for heart failure d. Lung disease with a home oxygen requirement e. Chronic kidney disease (eGFR <30 ml/min/1.7 m2 over a 3-month period) i. For adults (age ≥18), we will use the CKD-Epi equation which requires the measurement of serum creatinine only. ii. For children (age <18), we will use the bedside Schwartz (CKiD) formula. f. Nephrotic syndrome (>3.5 grams of protein per 24 hours) g. Cirrhosis with ascites

6. Women who are currently pregnant or planning pregnancy within 2 years.

7. Renal transplant recipient

8. Bedridden study participants (ECOG ≥ 3)

9. Uncorrected anatomical obstruction of the urinary tract

10. History of recurrent urinary tract infections (> 3 UTI/year proven by urine culture)

11. Exclusions due to medication use:

    1. Chronic use of lithium
    2. Long-term glucocorticoid use (> 7.5 mg prednisone daily for > 30 days prior to enrollment)
    3. Intake of narcotic medication on a daily basis for >30 days prior to enrollment
    4. Supplemental Vitamin C (> 1 g daily)

12. Individuals with stones that have developed after the initiation of medications that are strongly associated with USD such as carbonic anhydrase inhibitors (acetazolamide, topiramate, zonisamide), high dose vitamin C (> 1 g daily), high dose calcium supplementation (> 1,200 mg daily) AND who have discontinued or plan to discontinue these medications.

13. Individuals with stones composed of medications that may crystallize in the urine (guaifenesin, sulfonamides, triamterene, and the protease inhibitors indinavir and nelfinavir) AND who have discontinued or plan to discontinue these medications.

    Note: Individuals who are on long-term medications that increase the risk of stone disease, who cannot stop these medications due to other chronic conditions (e.g., HIV) and who may reduce their risk for stone recurrence through increased fluid intake, will be eligible to participate in the trial. Examples of these medications include:

    1. Carbonic anhydrase inhibitors (acetazolamide, topiramate, zonisamide)
    2. Medications that may crystallize in the urine (guaifenesin, sulfonamides, triamterene, and the protease inhibitors indinavir and nelfinavir).

14. Study participants <2 yrs life expectancy

15. Non-English Speakers

16. History of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

17. Anatomical urologic abnormalities including ileal conduits, horseshoe kidney, megaureter or solitary kidney.

18. Psychiatric conditions impairing compliance with the study

19. Vulnerable population (prisoner and/or cognitive impairment that the investigator feels will impact the study participant's ability to participate in the protocol)

20. Individual who will be unable to participate in the protocol in the judgment of the investigator.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention	Fluid prescription	Participants in the intervention arm will receive an individualized "fluid prescription", which will be the additional volume of fluid intake needed to maintain a study-specified urine output. This fluid will be consumed from and measured by a smart water bottle. The intervention arm also includes a behavioral program that consists of financial incentives and structured problem solving (SPS) to maintain the recommended fluid intake.
Intervention	Financial incentive	Participants in the intervention arm will receive an individualized "fluid prescription", which will be the additional volume of fluid intake needed to maintain a study-specified urine output. This fluid will be consumed from and measured by a smart water bottle. The intervention arm also includes a behavioral program that consists of financial incentives and structured problem solving (SPS) to maintain the recommended fluid intake.
Intervention	Structured Problem Solving	Participants in the intervention arm will receive an individualized "fluid prescription", which will be the additional volume of fluid intake needed to maintain a study-specified urine output. This fluid will be consumed from and measured by a smart water bottle. The intervention arm also includes a behavioral program that consists of financial incentives and structured problem solving (SPS) to maintain the recommended fluid intake.

Primary Outcome Measures

Name	Time	Method
Procedural intervention for symptomatic stone	From Baseline through 24 months.	From Baseline through 24 months; will be measured by the time from Baseline to a procedure to remove a symptomatic stone by a participant.
Any procedural intervention for removal of asymptomatic renal or ureteral stone	From Baseline through 24 months.	Will be measured by the time from Baseline to a procedure to remove an asymptomatic stone by a participant.
Stone passage observed and/or captured by the study participant.	From Baseline through 24 months.	Will be measured by the time from Baseline to the passage of 1 or more stones by a participant.

Secondary Outcome Measures

Name	Time	Method
Presence of lower urinary tract symptoms (Comprehensive Assessment of Self-reported Urinary Symptoms)	From Baseline through the Month 24 visit.	Will compare the results of the CASUS questionnaires completed throughout the study
Composite outcome: symptomatic stone recurrence, asymptomatic stone formation, increase of existing stone by ≥2 mm in any dimension detected by imaging	From Baseline through 24 months.
24 hour urine total volume	From Baseline through 24 months.	Will measure and compare 24 hour urine volumes from screening through 24 months.
Asymptomatic formation of new stone detected by imaging	From Baseline through 24 months.	Will be measured by the time from Baseline to the formation of an asymptomatic stone by a participant.
Costs of study interventions and treatments for USD during the follow-up period	Compared total between Baseline and the Month 24 visit.
Growth of existing stone by ≥ 2 mm in any dimension detected by imaging	From Baseline through 24 months.	Comparison of the size of any stone on first observation versus later observations or at passage. Will be measured primarily through imaging (CT scan or ultrasound).

Trial Locations

Locations (8)

University of Washington; 🇺🇸 Seattle, Washington, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Children's Hospital; 🇺🇸 Dallas, Texas, United States

Washington University, St. Louis; 🇺🇸 Saint Louis, Missouri, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

University of Texas Southwestern; 🇺🇸 Dallas, Texas, United States