Urinary Stones
Conditions
Keywords
Urinary Stone Disease, Kidney Stone, Urinary Calculi
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.
Interventions
BEHAVIORALFluid 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.
BEHAVIORALFinancial incentive
Participants in the Intervention Arm who meet their fluid intake goal on randomly selected days will receive a small payment for that day.
BEHAVIORALStructured 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.
Sponsors
Duke University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Investigator)
Masking description
The Principal Investigator and site investigators, along with the primary study statistician will remind blinded throughout the trial.
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Symptomatic Stone Event | Baseline through approximately 24 months | Having a symptomatic stone event was defined as meeting any 1 of 2 criteria - stone passage or a procedural intervention for a stone (whether the stone was causing symptoms or not). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Asymptomatic Formation of New Stone | Up to approximately 24 months | — |
| Number of Participants With Growth of Existing Stone by ≥ 2 mm in Any Dimension | Baseline through approximately 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 and ultrasound). |
| Number of Participants With Symptomatic Stone Recurrence, Asymptomatic Stone Formation, or Increase of Existing Stone by ≥2 mm in Any Dimension | Baseline through approximately 24 months | — |
| 24-hour Urine Total Volume | 6, 12, 18, and 24 months | — |
| Comprehensive Assessment of Self-Reported Urinary Symptoms (CASUS) | Baseline, 6, 12, 18, and 24 months | The CASUS is a tool used to assess lower urinary tract symptoms (LUTS) in individuals, providing a comprehensive evaluation of various urinary issues. It's designed to capture a wide range of symptoms, including storage, voiding, post-micturition, urgency, incontinence, and abnormal bladder sensations. The total score ranges from 0 to 38, where a higher score indicates greater urinary symptoms. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORCharles Scales, MD, MSHS
Duke University
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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.
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.
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. | 826 |
| 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. | 832 |
| Total | 1,658 |
Baseline characteristics
| Characteristic | Intervention | Total | Control |
|---|---|---|---|
| Age, Continuous | 45 years | 44 years | 44 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 46 Participants | 102 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 761 Participants | 1518 Participants | 757 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 19 Participants | 38 Participants | 19 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 22 Participants | 47 Participants | 25 Participants |
| Race (NIH/OMB) Black or African American | 55 Participants | 113 Participants | 58 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 21 Participants | 14 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 19 Participants | 11 Participants |
| Race (NIH/OMB) White | 732 Participants | 1451 Participants | 719 Participants |
| Region of Enrollment United States | 826 Participants | 1658 Participants | 832 Participants |
| Sex: Female, Male Female | 469 Participants | 946 Participants | 477 Participants |
| Sex: Female, Male Male | 357 Participants | 712 Participants | 355 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 826 | 2 / 832 |
| other Total, other adverse events | 12 / 826 | 2 / 832 |
| serious Total, serious adverse events | 0 / 826 | 0 / 832 |
Outcome results
Primary
Number of Participants With a Symptomatic Stone Event
Having a symptomatic stone event was defined as meeting any 1 of 2 criteria - stone passage or a procedural intervention for a stone (whether the stone was causing symptoms or not).
Time frame: Baseline through approximately 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Number of Participants With a Symptomatic Stone Event | 154 Participants |
| Control | Number of Participants With a Symptomatic Stone Event | 165 Participants |
95% CI: [0.77, 1.2]
Secondary
24-hour Urine Total Volume
Time frame: 6, 12, 18, and 24 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Intervention | 24-hour Urine Total Volume | 6 months | 1.81 L/day |
| Intervention | 24-hour Urine Total Volume | 12 months | 1.70 L/day |
| Intervention | 24-hour Urine Total Volume | 18 months | 1.70 L/day |
| Intervention | 24-hour Urine Total Volume | 24 months | 1.55 L/day |
| Control | 24-hour Urine Total Volume | 24 months | 1.47 L/day |
| Control | 24-hour Urine Total Volume | 6 months | 1.58 L/day |
| Control | 24-hour Urine Total Volume | 18 months | 1.55 L/day |
| Control | 24-hour Urine Total Volume | 12 months | 1.57 L/day |
Secondary
Comprehensive Assessment of Self-Reported Urinary Symptoms (CASUS)
The CASUS is a tool used to assess lower urinary tract symptoms (LUTS) in individuals, providing a comprehensive evaluation of various urinary issues. It's designed to capture a wide range of symptoms, including storage, voiding, post-micturition, urgency, incontinence, and abnormal bladder sensations. The total score ranges from 0 to 38, where a higher score indicates greater urinary symptoms.
Time frame: Baseline, 6, 12, 18, and 24 months
Population: Participants with CASUS data available at each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention | Comprehensive Assessment of Self-Reported Urinary Symptoms (CASUS) | 6 months | 6.23 score on a scale | Standard Deviation 3.197 |
| Intervention | Comprehensive Assessment of Self-Reported Urinary Symptoms (CASUS) | 18 months | 6.11 score on a scale | Standard Deviation 3.267 |
| Intervention | Comprehensive Assessment of Self-Reported Urinary Symptoms (CASUS) | 12 months | 6.26 score on a scale | Standard Deviation 3.442 |
| Intervention | Comprehensive Assessment of Self-Reported Urinary Symptoms (CASUS) | 24 months | 6.00 score on a scale | Standard Deviation 3.283 |
| Intervention | Comprehensive Assessment of Self-Reported Urinary Symptoms (CASUS) | Baseline | 6.11 score on a scale | Standard Deviation 3.298 |
| Control | Comprehensive Assessment of Self-Reported Urinary Symptoms (CASUS) | 24 months | 6.01 score on a scale | Standard Deviation 3.373 |
| Control | Comprehensive Assessment of Self-Reported Urinary Symptoms (CASUS) | Baseline | 5.94 score on a scale | Standard Deviation 3.311 |
| Control | Comprehensive Assessment of Self-Reported Urinary Symptoms (CASUS) | 6 months | 6.11 score on a scale | Standard Deviation 3.28 |
| Control | Comprehensive Assessment of Self-Reported Urinary Symptoms (CASUS) | 12 months | 6.05 score on a scale | Standard Deviation 3.517 |
| Control | Comprehensive Assessment of Self-Reported Urinary Symptoms (CASUS) | 18 months | 6.11 score on a scale | Standard Deviation 3.459 |
Secondary
Costs of Study Interventions and Treatments for USD During the Follow-up Period
To estimate study intervention costs, we will use a tool specifically designed to estimate costs associated with patient-centered interventions (R01NR011873). The costs of medical resource use will be assigned based on payment schedules (e.g., Medicare). To incorporate potential differences in health-related quality of life experienced by participants in the cost-effectiveness analysis, health state utilities will be estimated from existing literature. Full details of the economic analysis will be specified in the Economic Statistical Analysis Plan.
Time frame: Baseline through approximately 24 months
Secondary
Number of Participants With Asymptomatic Formation of New Stone
Time frame: Up to approximately 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Number of Participants With Asymptomatic Formation of New Stone | 82 Participants |
| Control | Number of Participants With Asymptomatic Formation of New Stone | 83 Participants |
95% CI: [0.72, 1.37]
Secondary
Number of Participants With Growth of Existing Stone by ≥ 2 mm in Any Dimension
Comparison of the size of any stone on first observation versus later observations or at passage. Will be measured primarily through imaging (CT scan and ultrasound).
Time frame: Baseline through approximately 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Number of Participants With Growth of Existing Stone by ≥ 2 mm in Any Dimension | 45 Participants |
| Control | Number of Participants With Growth of Existing Stone by ≥ 2 mm in Any Dimension | 32 Participants |
95% CI: [0.91, 2.29]
Secondary
Number of Participants With Symptomatic Stone Recurrence, Asymptomatic Stone Formation, or Increase of Existing Stone by ≥2 mm in Any Dimension
Time frame: Baseline through approximately 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Number of Participants With Symptomatic Stone Recurrence, Asymptomatic Stone Formation, or Increase of Existing Stone by ≥2 mm in Any Dimension | 232 Participants |
| Control | Number of Participants With Symptomatic Stone Recurrence, Asymptomatic Stone Formation, or Increase of Existing Stone by ≥2 mm in Any Dimension | 236 Participants |