Statin Induced ProteinuriaNCT00464503
Statins and the Urinary Proteome
A study testing Rosuvastatin-Crestor and Pravastatin-Pravasine in people with Statin Induced Proteinuria, run by Universiteit Antwerpen at 1 site in Belgium.
Trial summary
This study aims to investigate whether statines (rosuva- and pravastatin) induce tubular proteinuria. Read more about this study
- Who is it for?
- Ages 25 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Statin Induced Proteinuria
- What is being tested?
- Rosuvastatin-Crestor and Pravastatin-Pravasine
- How many people
- 7 participants
- Where
- 1 siteBelgium
- Study dates
- Sep 2007to Oct 2007
- Phase
- Interventional
- 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 25 to 65 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male, age range: 25 - 65 years
- Non-smoker
- Proteinuria: < 60 mg/24 hours
- Dipstick negative hematuria
- Bloodpressure: < 135 mm systolic, < 85 mm dyastolic
- Waist circumference: < 94 cm
Who cannot join
- Treatment with lipid-lowering drugs <1 year prior to the study
- Known history of diabetes or fasting glucose level: < 110 mg/dl
- Anti-hypertensive medication
- Life-expectancy < 1 year
- Pharmacological treatment with inotropes
- Acute or chronic inflammatory process, use if anti-inflammatory drugs or immunosuppression
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- Clinically active malignant disease
- Administration of any investigational drug within 30 days preceding study start and during the study
- Known intolerance to rosuvastatin or other statins
- Acute or chronic liver disease or ALAT>2.0 x upper limit of normal (ULN) at enrolment visit.
- Chronic muscle disease such as dermatomyositis or polymyositis or unexplained creatinine kinase (CK) above 3 x ULN at enrolment.
- Uncontrolled hypothyroidism as indicated by a thyroid stimulating hormone (TSH) > 2 x ULN at enrolment.
- Renal insufficiency: creatinine > 2.0mg/dl
- Known or suspect alcohol or drug abuse.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Statins on the Urinary Proteome
This study aims to investigate whether statines (rosuva- and pravastatin) induce tubular proteinuria.
Read the detailed description
The proximal tubular cells of the kidney are responsible for reabsorption of proteins from the tubular lumen. In a study using Opossum kidney (OK) cells, receptor-mediated protein endocytosis was reduced by statins, inhibitors of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, which are widely used for therapeutic reduction of plasma cholesterol levels (1). In a subsequent in vitro study protein endocytosis in human mixed proximal/distal kidney tubular cells was investigated in the presence and absence of statins to explore the possible clinical relevance of the observations in OK cells (2). The uptake of FITC-labeled albumin in these cultures occurred selectively into proximal tubular cells while it was absent in distal tubular/collecting duct cells. Three statins (simvastatin, pravastatin, and rosuvastatin) significantly inhibited the uptake of protein in a concentration-dependent way. This inhibitory effect of statins could be prevented by the co-addition of mevalonate, the product of HMG-CoA reductase. This effect was not the result of a statin-induced cytotoxicity since cell-viability was unaffected.
These data suggest that statins have the potential to inhibit albumin uptake by the human proximal nephron as a result of inhibition of HMG-CoA reductase in the proximal tubule cells. A reduced prenylation of some proteins critically involved in endocytosis has been put forward as the underlying mechanism.
Knowing these data it has been suggested that the occurrence of proteinuria in some patients treated with high statin doses is the result of a reduced tubular reabsorption/endocytosis of normally filtered proteins. To further explore the clinical relevance of such a mechanism, the composition of the urinary proteome under statin treatment will be investigated in normal healthy volunteers by two-dimensional gel electrophoresis based proteomics analysis.
- Conditions
- Statin Induced Proteinuria
- Being tested
- Rosuvastatin-Crestor, Pravastatin-Pravasine
- Keywords
- statins, proteinuria, proteomic analysis, healthy volunteers
- Medical subject headings
- Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rosuvastatin-CrestorDrug
Pravastatin-PravasineDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
The urinary protein pattern observed by difference gel electrophoresis based proteomics analysis in healthy subjects before and after the administration of rosuvastatin (Crestor®).
Secondary outcomes (4)
The urinary protein pattern observed by difference gel electrophoresis based proteomics analysis in healthy subjects before and during the administration of pravastatin (Pravasine®).
The urinary protein pattern observed by difference gel electrophoresis based proteomics analysis in healthy subjects during the administration of rosuvastatin (Crestor®) vs pravastatin (Pravasine®).
The urinary protein pattern observed by difference gel electrophoresis based proteomics analysis in healthy subjects during the administration of rosuvastatin (Crestor®) or pravastatin (Pravasine®) and after wash-out of these compounds.
The urinary albumin and retinol binding protein concentration before in healthy subjects, during and after administration of rosuvastatin (Crestor®) or pravastatin (Pravasine®).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2007 (estimated)
- Study startSep 2007
- Primary completionOct 2007
- Study completionOct 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Statin Induced ProteinuriaStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universiteit Antwerpen
- Sponsor type
- University, hospital or other
- Investigators
- Patrick C D'Haese, Prof, Study director, Universiteit Antwerpen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00464503
- Sponsor's protocol ID
- STAT-AZ-01
- Status last verified
- Apr 2008
- First submitted
- 20 Apr 2007
- Last updated
- 8 Apr 2008
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Statins on the Urinary Proteome
- ClinicalTrials.gov ID
- NCT00464503
- Acronym / sponsor ID
- STAT-AZ-01
- Conditions
- Statin Induced Proteinuria
- Keywords
- statins, proteinuria, proteomic analysis, healthy volunteers
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Universiteit AntwerpenUniversity, hospital or other
- Study start
- Sep 2007
- Primary completion
- Oct 2007 (actual)
- Study completion
- Oct 2007 (actual)
- First posted
- 23 Apr 2007 (estimated)
- 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.
This study aims to investigate whether statines (rosuva- and pravastatin) induce tubular proteinuria.
Detailed description
The proximal tubular cells of the kidney are responsible for reabsorption of proteins from the tubular lumen. In a study using Opossum kidney (OK) cells, receptor-mediated protein endocytosis was reduced by statins, inhibitors of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, which are widely used for therapeutic reduction of plasma cholesterol levels (1). In a subsequent in vitro study protein endocytosis in human mixed proximal/distal kidney tubular cells was investigated in the presence and absence of statins to explore the possible clinical relevance of the observations in OK cells (2). The uptake of FITC-labeled albumin in these cultures occurred selectively into proximal tubular cells while it was absent in distal tubular/collecting duct cells. Three statins (simvastatin, pravastatin, and rosuvastatin) significantly inhibited the uptake of protein in a concentration-dependent way. This inhibitory effect of statins could be prevented by the co-addition of mevalonate, the product of HMG-CoA reductase. This effect was not the result of a statin-induced cytotoxicity since cell-viability was unaffected.
These data suggest that statins have the potential to inhibit albumin uptake by the human proximal nephron as a result of inhibition of HMG-CoA reductase in the proximal tubule cells. A reduced prenylation of some proteins critically involved in endocytosis has been put forward as the underlying mechanism.
Knowing these data it has been suggested that the occurrence of proteinuria in some patients treated with high statin doses is the result of a reduced tubular reabsorption/endocytosis of normally filtered proteins. To further explore the clinical relevance of such a mechanism, the composition of the urinary proteome under statin treatment will be investigated in normal healthy volunteers by two-dimensional gel electrophoresis based proteomics analysis.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
Who may qualify
- Ages
- 25 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male, age range: 25 - 65 years
- Non-smoker
- Proteinuria: < 60 mg/24 hours
- Dipstick negative hematuria
- Bloodpressure: < 135 mm systolic, < 85 mm dyastolic
Key exclusion criteria (14 listed)
- Treatment with lipid-lowering drugs <1 year prior to the study
- Known history of diabetes or fasting glucose level: < 110 mg/dl
- Anti-hypertensive medication
- Life-expectancy < 1 year
- Pharmacological treatment with inotropes
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 |
|---|---|---|
| Rosuvastatin-Crestor | Drug | – |
| Pravastatin-Pravasine | Drug | – |
Primary outcome
The urinary protein pattern observed by difference gel electrophoresis based proteomics analysis in healthy subjects before and after the administration of rosuvastatin (Crestor®).
4 secondary outcomes
The urinary protein pattern observed by difference gel electrophoresis based proteomics analysis in healthy subjects before and during the administration of pravastatin (Pravasine®).
The urinary protein pattern observed by difference gel electrophoresis based proteomics analysis in healthy subjects during the administration of rosuvastatin (Crestor®) vs pravastatin (Pravasine®).
The urinary protein pattern observed by difference gel electrophoresis based proteomics analysis in healthy subjects during the administration of rosuvastatin (Crestor®) or pravastatin (Pravasine®) and after wash-out of these compounds.
The urinary albumin and retinol binding protein concentration before in healthy subjects, during and after administration of rosuvastatin (Crestor®) or pravastatin (Pravasine®).
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 8 Apr 2008.
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.
Patrick C D'Haese, Prof study director
Universiteit Antwerpen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Rosuvastatin-Crestor and Pravastatin-Pravasine in people with Statin Induced Proteinuria, run by Universiteit Antwerpen at 1 site in Belgium.
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 14 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 8 Apr 2008. 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 Belgium. 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?
The urinary protein pattern observed by difference gel electrophoresis based proteomics analysis in healthy subjects before and after the administration of rosuvastatin (Crestor®).. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Apr 2008.