This Study Evaluates the Superiority of Daily Self-pH Monitorization of Lit-control®pH Meter Compared to the Monitorization of Reactive Strips (Standard of Care).

Study Overview
=================
Brief Summary
-----------------
This study evaluates the superiority of daily self-pH monitorization of Lit-control®pH meter compared to the monitorization of reactive strips (standard of care).

Detailed Description
-----------------
Cystinuria is a disease of autosomal recessive inheritance. This disease belongs to the so-called orphan diseases although its prevalence may change depending on the country. It is known that urinary pH is a risk factor for the formation of cystine crystals because their solubility is pH-dependent. In different studies it has been shown that the solubility of cystine in urine increases when alkalinizing urinary pH, thus reducing the likelihood of crystal formation. Therefore, the control of urinary pH along with hygienic-dietetic measures that alkalize the urine or decrease the urinary concentration of cystine (abundant intake of water, food, etc.) are highly recommended as a preventive method to prevent the formation of cystine crystals whose retention and growth results in the formation of stones. The Lit-control®pH Meter is a pH meter that allows a patient to self-monitor its urinary pH in a comfortable and simple way. With this tool the patient is able to know if his urinary pH is within the recommended limits. In other medical fields it has been observed that home monitoring of clinically relevant physiological parameters is a way of empowering the patient that can positively affect their attitudes and behaviors (adherence to received treatment, quality of life) and potentially improve their medical condition. Specifically, in patients with chronic diseases, the self-monitoring has been associated with a significant reduction in hospitalizations and hospital readmissions.

Official Title
-----------------
Randomized, Controlled and Opened Trial on the Impact of the Use of a pH-Meter on the Domiciliary Control of the Urinary pH as Adjuvant to the Treatment of Cystinuric Patients

Conditions
-----------------
Cystinuria

Intervention / Treatment
-----------------
* Device: Lit-control®pH Meter
* Diagnostic Test: Reactive strips


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥18 years old. Cystinuric patients, with or without urinary lithiasis at the time of inclusion. Patients who accept their participation in the study and give their informed consent. Exclusion Criteria: Patients with pathologies that require pH control other than the one established in the study protocol to avoid the formation of kidney stones.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will receive the product for home pH monitoring, but they will keep following the doctor's recommendations indicated in the usual clinical practice. The proportion of patients will be 1: 1 between the study group (Lit-control®pH Meter) and the control group (test strips).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lit-control®pH Meter<br>The control of the urinary pH will be carried out twice a day: with the first urine in the morning and in the evening-night (approximately every 12h and at the same time). Measurements will be performed using the Lit-control®pH Meter device. | Device: Lit-control®pH Meter<br>* Alkalinization products will be used as standard clinical practice together with the pH monitoring through the Lit-control®pH Meter.<br>|
| Placebo Comparator: Reactive strips<br>The control of the urinary pH will be carried out twice a day: with the first urine in the morning and in the evening-night (approximately every 12h and at the same time). Measurements will be performed using the reactive strips. | Diagnostic Test: Reactive strips<br>* Alkalinization products will be used as standard clinical practice together with the pH monitoring through the reactive strips.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of days with pH levels within range 7 and 8, during 6 months of home self-monitoring. | Urinary pH measurement | 183 measurements (morning) in 6 months. | 
| Percentage of days with pH levels within range 7 and 8, during 6 months of home self-monitoring. | Urinary pH measurement | 183 measurements (afternoon) in 6 months. | 
| Measurement of the volume of crystalluria. | volume of crystalluria | 1 measurement at the moment of enrollment | 
| Measurement of the volume of crystalluria. | volume of crystalluria | 1 measurement at 6 months | 
| Blood: DNA extraction. | Extraction of DNA for genetic study of mutations for cystinuria. | 1 measurement at the moment of enrollment | 
| Sediment analysis for the determination of urinary infection. | Sediment analysis for the determination of Ulcer Index (UI) | 1 measurement at the moment of enrollment | 
| Sediment analysis for the determination of urinary infection. | Sediment analysis for the determination of UI | 1 measurement at 6 months | 
| Total time within the margins established as safe in the pH control (months). | Amount of time within the pH margins established as safe | 1 measurement through study completion [up to 6 months] | 
| Adherence level in pH measurements | % compliance of the pH measurements | Through study completion, fraction of pH measurements on the total possible. [up to 6 months] | 
| Adherence level to treatment | % of the intakes of the medication. | Through study completion, fraction of intakes on the total possible. [up to 6 months] | 
| Total number of adverse events reported. | Amount of adverse events reported | Through study completion, number of events. [up to 6 months] | 
| Blood Analysis. Glucose | Glucose in mmol/L | Change from Baseline measurement at 6 months | 
| Blood Analysis. Calcium phosphate | calcium phosphate in µmol/L | Change from Baseline measurement at 6 months | 
| Blood Analysis. Estimated Glomolecular Filtration Chronic Kidney Disease Epidemiology Collaboration (FG CKD-EPI) | estimated FG CKD-EPI | Change from Baseline measurement at 6 months | 
| Blood Analysis. Cystatin | cystatin in mg/L (to be measured only if estimated FG> 45 or <ml /min / 1.73 m2 and albumin / creatinine in the urine <3 mg / mmol) | Change from Baseline measurement at 6 months | 
| Blood Analysis. Creatinine | creatinine in µmol/L | Change from Baseline measurement at 6 months | 
| Blood Analysis. Urate | urate in μmol/L | Change from Baseline measurement at 6 months | 
| 24h Urine Analysis. Weight | Weight in kg | Change from Baseline measurement at 6 months | 
| 24h Urine Analysis. Size | Size in m | Change from Baseline measurement at 6 months | 
| 24h Urine Analysis. Urinary volume | Urinary volume in L | Change from Baseline measurement at 6 months | 
| 24h Urine Analysis. Calcium phosphate | calcium phosphate in µmol/L | Change from Baseline measurement at 6 months | 
| 24h Urine Analysis. Citrate | citrate in μmol/L | Change from Baseline measurement at 6 months | 
| 24h Urine Analysis. Urate | urate in μmol/L | Change from Baseline measurement at 6 months | 
| 24h Urine Analysis. Magnesium | magnesium in μmol/L | Change from Baseline measurement at 6 months | 
| 24h Urine Analysis. Sodium | sodium in μmol/L | Change from Baseline measurement at 6 months | 
| 24h Urine Analysis. BMI | weight and height will be combined to report BMI in kg/m^2 | Change from Baseline measurement at 6 months | 
| 24h Urine Analysis. Potassium | potassium in μmol/L | Change from Baseline measurement at 6 months | 
| 24h Urine Analysis. Urea | urea in µmol/L | Change from Baseline measurement at 6 months | 
| Urine for the study of crystalluria. Schedule | First urine of the morning (totality) for the study of crystalluria. Patient will provide the last hour of urination and hour of urine obtention in the morning. | Change from Baseline measurement at 6 months | 
| Urine for the study of crystalluria. Crystalline volume | overall crystalline volume (μm3 / mL) | Change from Baseline measurement at 6 months | 
| Urine for the study of crystalluria. Crystals | type and number of crystals (crystals / μL) | Change from Baseline measurement at 6 months | 
| Urine for the study of crystalluria. Urine volume | urine volume in L | Change from Baseline measurement at 6 months | 
| Urine for the study of crystalluria. pH | pH | Change from Baseline measurement at 6 months | 
| Urine for the study of crystalluria. Size | size in μm | Change from Baseline measurement at 6 months | 
| Urine for the study of crystalluria. Density | Density in mg / mL. | Change from Baseline measurement at 6 months | 
| Urine for the study of crystalluria. Aggregation | aggregation | Change from Baseline measurement at 6 months | 
| Urine for the study of crystalluria. Twinning | twinning | Change from Baseline measurement at 6 months | 
| Urine for the study of crystalluria. Quotient | Quotient albumin / creatinine | Change from Baseline measurement at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sociodemographic and anthropometric questionnaire. | Family and personal background and general data (sex, age, etc.). | 1 day of enrollment | 
| Patient satisfaction questionnaire with the pH measurement method | Visual Analogue Scale ranging from 1 (very dissatisfied) to 10 (very satisfied) | 3 times in 6 months | 
| Physician satisfaction questionnaire with the pH measurement method | Likert Scale with 4 categories: very dissatisfied, dissatisfied, satisfied, very satisfied | 3 times in 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cystinuria, pH Control