Effect of Urine Alkalinazation on Urinary Inflammatory Markers in Patients With Cystinuria

• ClinicalTrials.gov Identifier: NCT03836144
• Recruitment Status: Recruiting
• First Posted: February 11, 2019
• Last Update Posted: February 11, 2019
• Sponsor: European Georges Pompidou Hospital
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; Sponsor Name Pending
• Information provided by (Responsible Party): Marie Courbebaisse, European Georges Pompidou Hospital

Tracking Information

• First Submitted Date: January 21, 2019
• First Posted Date: February 11, 2019
• Last Update Posted Date: February 11, 2019
• Actual Study Start Date: April 2, 2015
• Estimated Primary Completion Date: December 31, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 7, 2019)

Change from baseline urine inflammatory profile after 3 months of alkalizing treatment using mass spectrometry in patients with cystinuria. [ Time Frame: at inclusion and after three months of the usual alkalizing treatment for the patients with cystinuria ]

Study of urine inflammatory biomarkers profile using mass spectrometry to determine if the alkalizing treatment is susceptible to modify the urine inflammatory profile. Proteases inhibitors will be added to the urine sample immediately after urination. Urine will then be frozen at -80°C until mass spectrometry analysis. Mass spectrometry will determine the differential expression of all the proteins present the urine sample. For the purpose of the present study, the investigators will focus on the expression of inflammatory biomarkers among them MMP9 (matrix metallopeptidase), Myeloperoxydase, Proteinase 3, Neutrophil Elastase, Cathepsine G, LSP1 (lymphocyte specific protein), Fibrinogen beta and gamma chains. The aim of mass spectrometry is to detect the presence of proteins in the urine sample and to assess the differential levels of expression of the detected proteins but not to precisely measure the urine concentration of the detected proteins.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: February 7, 2019)

• Assessment of urine inflammatory profile in controls groups using mass spectrometry. [ Time Frame: at inclusion for patients with a nephrolithiasis not due to cystinuria and in patients an inflammatory nephropathy of glomerular or tubulo interstitial origin ]
  Study of urine inflammatory biomarkers with mass spectrometry in control groups to determine if the urine inflammatory profile is specific to cystinuria. Proteases inhibitors will be added to the urine sample immediately after urination. Urine will then be frozen at -80°C until analysis. Mass spectrometry will determine the differential expression of all the proteins present the urine sample. For the purpose of the present study, the investigators will focus on the expression of inflammatory biomarkers. The aim of mass spectrometry is to detect the presence of proteins in the urine sample and to assess the differential levels of expression of the detected proteins but not to precisely measure the urine concentration of these proteins. Moreover, urine analysis by mass spectrometry will detect all urinary proteins and the investgators do exclude to find unexpected proteins. For those reasons, urine analysis by mass spectrometry is a unique outcome.
• Study of crystalluria (presence of crystals in urine) to assess nephrolithiasis activity. [ Time Frame: at inclusion for these two groups and after three months of the usual alkalizing treatment for the patients with cystinuria ]
  Assessment of the presence of crystals in the second morning urine sample in patients with cystinuria and in patients with a nephrolithiasis not due to cystinuria, to assess nephrolithiasis activity.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: February 7, 2019)

• Presence of stones in the renal cavities or in the urinary tract using ultrasonograhy. [ Time Frame: at inclusion for these two groups and after three months of the usual alkalizing treatment for the patients with cystinuria ]
  assessment of the presence of urinary stones using ultrasonogrpahy in patients with cystinuria and in patients with a nephrolithiasis not due to cystinuria.
• Blood CRP concentrations to assess systemic inflammation [ Time Frame: at inclusion for all groups and and after three months of the usual alkalizing treatment for the patients with cystinuria ]
  Blood CRP concentration (mg/L)

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Effect of Urine Alkalinazation on Urinary Inflammatory Markers in Patients With Cystinuria
• Official Title: Effect of Urine Alkalinazation on Urinary Inflammatory Markers Analyzed Using Mass Spectrometry in Patients With Cystinuria

Brief Summary

It has recently been described the presence of a urinary inflammatory signature in patients with cystinuria, the most common cause of renal lithiasis of genetical origin. These data are very innovative in this pathology but deserve further studies to establish the specificity of this inflammatory signature in patients with cystinuria compared to other nephropathies and other renal lithiasis diseases. Moreover, the effect of the usual treatment of cystinuria (namely urine alkalanization) on urinary inflammatory biomarkers deserves to be tested.

The objectives of the present study are: i) To study the urinary inflammatory profile by mass spectrometry (a very efficient tool to detect and identify proteins) in patients with cystinuria and in patients with lithiasis of other origin and in patients with inflammatory renal disease ; ii) To study the potential effect of urine alkalinazation with potassium citrate (usual treatment according to European recommendations) on the inflammatory signature of patients with cystinuria. To this aim, urine of non treated cystinuric patients will be collected before treatement initiation and 3 months after the start of the alkalizing treatment.

• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples Without DNA

Description:

urine

• Sampling Method: Non-Probability Sample

Study Population

Patients with cystinuria, as well as patients with renal lithiasis not due to cystinuria and patients with an inflammatory renal pathology will be selected by the investigators of the study during their usual medical consultation.

At that time, patients will be given the information note and will be asked to sign the written informed consent.

Condition

• Cystinuria
• Renal Lithiasis
• Glomerulonephritis
• Interstitial Nephritis

Intervention

Dietary Supplement: Potassium citrate

Other Name: Sodium bicarbonate

Study Groups/Cohorts

• Cystinuria
  10 patients with cystinuria. Experimental. Urine collected before treatment initiation and 3 months after. Treatment: Usual alkalizing treatment using oral potassium citrate. The initial dosage will be 4 g/day divided into 3 to 4 oral daily doses. If the objective of urinary pH is not reached after the first two weeks of treatment, the dose will be increased by 2 grams (6 grams total). If the urinary pH remains below 7.5 after 2 weeks with 6 grams of potassium citrate per day, the alkalizing treatment will then be supplemented with oral sodium bicarbonate in the form of Vichy water or officinal preparation. This treatment is the usual treatment recommended for cystinuria .
  Intervention: Dietary Supplement: Potassium citrate
• Non cystinuria nephrolithiasis
  20 patients with a nephrolithiasis not due to cystinuria. Control group. Urine collected once to study biomarkers of inflammation No intervention.
• Inflammatory nephropathy

  10 patients with an inflammatory nephropathy of glomerular or tubulo interstitial origin (confirmed by renal biopsy).

  Control group. Urine collected once to study biomarkers of inflammation. No intervention.

Publications *

• Bourderioux M, Nguyen-Khoa T, Chhuon C, Jeanson L, Tondelier D, Walczak M, Ollero M, Bekri S, Knebelmann B, Escudier E, Escudier B, Edelman A, Guerrera IC. A new workflow for proteomic analysis of urinary exosomes and assessment in cystinuria patients. J Proteome Res. 2015 Jan 2;14(1):567-77. doi: 10.1021/pr501003q. Epub 2014 Nov 12.
• Prot-Bertoye C, Lebbah S, Daudon M, Tostivint I, Bataille P, Bridoux F, Brignon P, Choquenet C, Cochat P, Combe C, Conort P, Decramer S, Doré B, Dussol B, Essig M, Gaunez N, Joly D, Le Toquin-Bernard S, Méjean A, Meria P, Morin D, N'Guyen HV, Noël C, Normand M, Pietak M, Ronco P, Saussine C, Tsimaratos M, Friedlander G, Traxer O, Knebelmann B, Courbebaisse M; French Cystinuria Group. CKD and Its Risk Factors among Patients with Cystinuria. Clin J Am Soc Nephrol. 2015 May 7;10(5):842-51. doi: 10.2215/CJN.06680714. Epub 2015 Feb 25.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 7, 2019): 40
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2021
• Estimated Primary Completion Date: December 31, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• age superior or equal to 18 years
• patient able to understand the information note and to sign the informed consent
• patient with an Health coverage
• no current urinary tract infection (assessed by a cytobacteriological examination of the urine)
• For the cystinuria group: patient with cystinuria not yet treated or for whom the alkalizing treatment or the cystein binding thiol agents have been discontinuated for at least 3 months AND with an estimated GFR (using the MDRD formula) greater than 60 ml/min/1.73m2.
• For the control groups: patient presenting either a renal lithiasis not due to cystinuria, or an inflammatory renal pathology confirmed by an anterior renal biopsy (glomerulonephritis or interstitial nephritis) AND with an estimated GFR (using the MDRD formula) greater than 30 ml/ min/1.73m2.

Exclusion Criteria:

• Cystinuric patient already treated (whatever the treatment)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Marie COURBEBAISSE, MD, PhD; +33 1 56 09 39 73; marie.courbebaisse@aphp.fr

Contact: Caroline BERTOYE, MD; +33 1 56 09 39 69; caroline.bertoye@aphp.fr

• Listed Location Countries: France

Administrative Information

• NCT Number: NCT03836144
• Other Study ID Numbers: EuropeanGPH
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Marie Courbebaisse, European Georges Pompidou Hospital
• Study Sponsor: European Georges Pompidou Hospital

Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France
• Sponsor Name Pending

• Investigators: Not Provided
• PRS Account: European Georges Pompidou Hospital
• Verification Date: February 2019