CystinuriaNCT03836144
Effect of Urine Alkalinazation on Urinary Inflammatory Markers in Patients With Cystinuria
An observational study of Cystinuria and Renal Lithiasis, run by European Georges Pompidou Hospital at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cystinuria, Renal Lithiasis, Glomerulonephritis
- What is being tested?
- Potassium citrate
- Type of treatment
- Pill or oral medicine
- How many people
- 63 participants
- Where
- 1 siteFrance
- Study dates
- 2 Apr 2015to 31 Dec 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- Cystinuric patient already treated (whatever the treatment)
Trial locations and contacts
1 site in 1 country.
France1 site
Eurpean Georges Pompidou Hospital
Paris, Île-de-France Region, 75015
About this study
Official title: Effect of Urine Alkalinazation on Urinary Inflammatory Markers Analyzed Using Mass Spectrometry in Patients With Cystinuria
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.
- Being tested
- Potassium citrate
- Keywords
- Mass spectrometry, Cystinuria, Inflammation, Nephrolithiasis
- Medical subject headings
- Cystinuria, Nephrolithiasis, Glomerulonephritis, Nephritis, Interstitial, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Potassium citrateDietary supplement
Also called Sodium bicarbonate
| Study group | Role | What they receive |
|---|---|---|
| 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 . Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline urine inflammatory profile after 3 months of alkalizing treatment using mass spectrometry in 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.
Measured: at inclusion and after three months of the usual alkalizing treatment for the patients with cystinuria
Secondary outcomes (2)
Assessment of urine inflammatory profile in controls groups using mass spectrometry.
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.
Measured: 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 crystalluria (presence of crystals in urine) to assess nephrolithiasis activity.
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.
Measured: at inclusion for these two groups and after three months of the usual alkalizing treatment for the patients with cystinuria
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2019
- Study start2 Apr 2015
- Primary completion31 Jan 2020
- Study completion31 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for CystinuriaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- European Georges Pompidou Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Sponsor Name Pending
- Responsible party
- Principal investigator, Marie Courbebaisse, European Georges Pompidou Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03836144
- Sponsor's protocol ID
- EuropeanGPH
- Status last verified
- Mar 2022
- First submitted
- 21 Jan 2019
- Last updated
- 22 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 25365230Prot-Bertoye C, Lebbah S, Daudon M, Tostivint I, Bataille P, Bridoux F, Brignon P, Choquenet C, Cochat P, Combe C, Conort P, Decramer S, Dore B, Dussol B, Essig M, Gaunez N, Joly D, Le Toquin-Bernard S, Mejean A, Meria P, Morin D, N'Guyen HV, Noel 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.
PubMed 25717071
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Urine Alkalinazation on Urinary Inflammatory Markers Analyzed Using Mass Spectrometry in Patients With Cystinuria
- ClinicalTrials.gov ID
- NCT03836144
- Acronym / sponsor ID
- EuropeanGPH
- Keywords
- Mass spectrometry, Cystinuria, Inflammation, Nephrolithiasis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- European Georges Pompidou HospitalUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Sponsor Name Pending
- Study start
- 2 Apr 2015 (actual)
- Primary completion
- 31 Jan 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 11 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cystinuria | – | Dietary Supplement: Potassium citrate10 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 . |
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (1 listed)
- Cystinuric patient already treated (whatever the treatment)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Potassium citrateAlso: Sodium bicarbonate | Dietary supplement | Cystinuria |
Primary outcome
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.
2 secondary outcomes
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 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2022.
- Results publication: PubMed 25365230Bourderioux 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.
- Results publication: PubMed 25717071Prot-Bertoye C, Lebbah S, Daudon M, Tostivint I, Bataille P, Bridoux F, Brignon P, Choquenet C, Cochat P, Combe C, Conort P, Decramer S, Dore B, Dussol B, Essig M, Gaunez N, Joly D, Le Toquin-Bernard S, Mejean A, Meria P, Morin D, N'Guyen HV, Noel 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cystinuria and Renal Lithiasis, run by European Georges Pompidou Hospital at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03836144, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2022.