Prevention of Urinary Stones With Hydration (PUSH)

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Urinary Stones	Behavioral: Fluid prescription; Behavioral: Financial incentive; Behavioral: Structured Problem Solving	Not Applicable

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 Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	1642 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Investigator)
Masking Description:	The Principal Investigator and site investigators, along with the primary study statistician will remind blinded throughout the trial.
Primary Purpose:	Prevention
Official Title:	Prevention of Urinary Stones With Hydration
Actual Study Start Date :	September 13, 2017
Estimated Primary Completion Date :	September 1, 2021
Estimated Study Completion Date :	September 1, 2021

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Intervention; 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.	Behavioral: Fluid prescription; The additional amount of fluid that the participant will need to consume each day, using the smart water bottle, in order to meet the study-specified urine output. This fluid is in addition to any other sources of fluid (ex. cups of coffee, bottled sports drink) that the participant consumes each day.; Behavioral: Financial incentive; Participants in the Intervention Arm who meet their fluid intake goal on randomly selected days will receive a small payment for that day.; Behavioral: Structured Problem Solving; Structure Problem Solving involves interactions with health coaches to help participants develop feasible solutions to overcoming personal barriers to maintaining the prescribed fluid intake.
No Intervention: Control; Participants in the control arm will receive standard care instructions according to American Urological Association (AUA) guidelines to increase overall fluid consumption to achieve study-specified urine output. They will also receive a "smart" water bottle with capability to self-monitor their fluid intake.

Outcome Measures

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Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Asymptomatic formation of new stone detected by imaging [ Time Frame: From Baseline through 24 months. ]
   Will be measured by the time from Baseline to the formation of an asymptomatic stone by a participant.
2. Change in size of existing stone by ≥ 2 mm in any dimension detected by imaging [ Time Frame: 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).
3. Composite outcome: symptomatic stone recurrence, asymptomatic stone formation, increase of existing stone by ≥2 mm in any dimension detected by imaging [ Time Frame: From Baseline through 24 months. ]
4. 24 hour urine total volume [ Time Frame: From Baseline through 24 months. ]
   Will measure and compare 24 hour urine volumes from screening through 24 months.
5. Costs of study interventions and treatments for USD during the follow‐up period [ Time Frame: Compared total between Baseline and the Month 24 visit. ]
6. Presence of lower urinary tract symptoms (Comprehensive Assessment of Self‐reported Urinary Symptoms) [ Time Frame: From Baseline through the Month 24 visit. ]
   Will compare the results of the CASUS questionnaires completed throughout the study

Eligibility Criteria

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Ages Eligible for Study:	12 Years and older (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Aged ≥ 12 years
2. At least 1 symptomatic stone event (passage or procedural intervention) within 3 years prior to enrollment

3. Low 24‐hr urine volume

   1. ≥18 years old: <1.8 L/day
   2. <18 years old: <20 ml/Kg/day up to 1.8L/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

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 taking 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.

Contacts and Locations

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Contacts

Contact: Laura Johnson	919-323-6831	laura.m.johnson@duke.edu
Contact: Sharon Settles		sharon.settles@duke.edu

Locations

United States, Missouri
Washington University, St. Louis	Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Juanita Taylor 314-362-8045 PUSH@wustl.edu
Contact: Aleksandra Klim 314-747-9781 PUSH@wustl.edu
Principal Investigator: Henry Lai, MD
Principal Investigator: Alana Desai, MD
United States, Pennsylvania
University of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Emily Funsten 215-573-8070 Emily.Funsten@uphs.upenn.edu
Principal Investigator: Peter Reese, MD, MSCE
Children's Hospital of Philadelphia	Recruiting
Philadelphia, Pennsylvania, United States, 19146
Contact: Brittney Henderson 267-426-1337 hendersob2@email.chop.edu
Principal Investigator: Gregory Tasian, MD, MSc, MSCE
United States, Texas
Children's Hospital	Recruiting
Dallas, Texas, United States, 75390
Contact: Martinez Hill 214-456-0279 MARTINEZ.HILL@childrens.com
Principal Investigator: Naim Maalouf, MD
University of Texas Southwestern	Recruiting
Dallas, Texas, United States, 75390
Contact: Cynthia Rangel 214-645-8787 Cynthia.Rangel@UTSouthwestern.edu
Principal Investigator: Naim Maalouf, MD
Sub-Investigator: Linda Baker, MD
United States, Washington
University of Washington	Recruiting
Seattle, Washington, United States, 98195
Contact: Holly Covert 206-616-5170 coverh@uw.edu
Principal Investigator: Jonathan Harper, MD
Principal Investigator: Hunter Wessells, MD, FACS

Sponsors and Collaborators

Duke University

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

Principal Investigator:	Charles Scales, MD, MSHS	Duke University

More Information

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Additional Information:

The Urinary Stone Disease Research Network (USDRN) website. The USDRN is the program conducting the PUSH study. 

Responsible Party:	Duke University
ClinicalTrials.gov Identifier:	NCT03244189 History of Changes
Other Study ID Numbers:	Pro00083271; 1U01DK110988 ( U.S. NIH Grant/Contract )
First Posted:	August 9, 2017
Last Update Posted:	June 4, 2018
Last Verified:	September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	Data and samples, for subjects who consent to sharing, will be sent to the NIDDK Data and Biological Samples Repository following database lock.
Supporting Materials:	Study Protocol; Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
Time Frame:	2 years after the last visit of the last participant randomized.
Access Criteria:	Anyone with access to the NIDDK Data and Biological Samples Repository
URL:	https://www.niddkrepository.org/home/

Studies a U.S. FDA-regulated Drug Product:		No
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Duke University:

Urinary Stone Disease; Kidney Stone; Urinary Calculi

Additional relevant MeSH terms:

Calculi; Urinary Calculi; Urolithiasis; Pathological Conditions, Anatomical; Urologic Diseases