- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00346918
Sirolimus (Rapamune®) for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
February 26, 2014 updated by: University of Zurich
Sirolimus (Rapamune®) for Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD): a Randomized Controlled Study.
The aim of our study is to investigate whether Rapamune used at a low dose (2 mg/d) retards cyst growth and slows renal functional deterioration in patients with ADPKD.
Study Overview
Status
Completed
Intervention / Treatment
Detailed Description
Currently there is no treatment for ADPKD other than supportive care and blood pressure control.
Usually dialytic treatment or renal transplantation becomes necessary when the disease has progressed to end-stage renal failure.We and others could demonstrate that rapamycin, a classical mTOR inhibitor, retards cyst growth and preserves renal function in a rodent model of ADPKD.
The aim of our study is to investigate whether Rapamune (2 mg/d) retards cyst growth and slows renal functional deterioration in patients with ADPKD.
We anticipate that we can slow disease progression and delay the need for chronic renal replacement therapy by the inhibition of mTOR with Rapamune.
This is a 24-month prospective, controlled, open label study with 2 parallel groups in patients with ADPKD.
Patients will be randomized at a 1:1 ratio to one of the 2 treatment arms.
Primary endpoint is percentage change of renal volume measured by high resolution magnetic resolution imaging.
Study Type
Interventional
Enrollment (Actual)
100
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Zurich, Switzerland, 8091
- University Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 40 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male or female ADPKD patient between 18 and 40 years of age
- measured GFR higher than 70 ml/min 1.73m2
- documented kidney volume progression
- informed consent
Exclusion Criteria:
- Female of childbearing potential who is planning to become pregnant, who is pregnant and/or lactating, who is unwilling to use effective means of contraception
- increased liver enzymes (2-fold above normal values)
- hypercholesterolemia (fasting cholesterol > 8 mmol/l) or hypertriglyceridaemia (> 5 mmol/l) not controlled by lipid lowering therapy
- granulocytopenia (white blood cell < 3,000/mm3) or thrombocytopenia (platelets < 100,000/mm3),
- infection with hepatitis B or C, HIV
- any past or present malignancy
- mental illness that interfere with the patient ability to comply with the protocol
- drug or alcohol abuse within one year of baseline
- co-medication with strong inhibitor of CYP3A4 and or P-gp like voriconazole, ketoconazole, diltiazem, verapamil, erythromycin
- co-medication with strong CYP3A4 and or P-gp inductor like rifampicin
- known hypersensitivity to macrolides or Rapamune
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: 1
Treatment of hypertension, cyst infections and flank pain
|
Standard
Other Names:
|
Active Comparator: 2
Sirolimus plus Standard Treatment
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Standard plus Sirolimus
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
renal volume measured by high resolution magnetic resolution imaging
Time Frame: 1.5 yrs
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1.5 yrs
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
GFR
Time Frame: 1.5 yrs
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1.5 yrs
|
Adverse event
Time Frame: 1.5 yrs
|
1.5 yrs
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Andreas L. Serra, MD, University of Zurich
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Wahl PR, Serra AL, Le Hir M, Molle KD, Hall MN, Wuthrich RP. Inhibition of mTOR with sirolimus slows disease progression in Han:SPRD rats with autosomal dominant polycystic kidney disease (ADPKD). Nephrol Dial Transplant. 2006 Mar;21(3):598-604. doi: 10.1093/ndt/gfi181. Epub 2005 Oct 12.
- Serra AL, Poster D, Kistler AD, Krauer F, Raina S, Young J, Rentsch KM, Spanaus KS, Senn O, Kristanto P, Scheffel H, Weishaupt D, Wuthrich RP. Sirolimus and kidney growth in autosomal dominant polycystic kidney disease. N Engl J Med. 2010 Aug 26;363(9):820-9. doi: 10.1056/NEJMoa0907419. Epub 2010 Jun 26.
- Braun M, Young J, Reiner CS, Poster D, Wuthrich RP, Serra AL. Ovarian toxicity from sirolimus. N Engl J Med. 2012 Mar 15;366(11):1062-4. doi: 10.1056/NEJMc1113145. No abstract available.
- Braun M, Young J, Reiner CS, Poster D, Krauer F, Kistler AD, Kristanto P, Wang X, Liu Y, Loffing J, Andreisek G, von Eckardstein A, Senn O, Wuthrich RP, Serra AL. Low-dose oral sirolimus and the risk of menstrual-cycle disturbances and ovarian cysts: analysis of the randomized controlled SUISSE ADPKD trial. PLoS One. 2012;7(10):e45868. doi: 10.1371/journal.pone.0045868. Epub 2012 Oct 10.
- Serra AL, Kistler AD, Poster D, Krauer F, Senn O, Raina S, Pavik I, Rentsch K, Regeniter A, Weishaupt D, Wuthrich RP. Safety and tolerability of sirolimus treatment in patients with autosomal dominant polycystic kidney disease. Nephrol Dial Transplant. 2009 Nov;24(11):3334-42. doi: 10.1093/ndt/gfp280. Epub 2009 Jun 13.
- Serra AL, Kistler AD, Poster D, Struker M, Wuthrich RP, Weishaupt D, Tschirch F. Clinical proof-of-concept trial to assess the therapeutic effect of sirolimus in patients with autosomal dominant polycystic kidney disease: SUISSE ADPKD study. BMC Nephrol. 2007 Sep 15;8:13. doi: 10.1186/1471-2369-8-13.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2006
Primary Completion (Actual)
January 1, 2010
Study Completion (Actual)
June 1, 2010
Study Registration Dates
First Submitted
June 22, 2006
First Submitted That Met QC Criteria
June 28, 2006
First Posted (Estimate)
June 30, 2006
Study Record Updates
Last Update Posted (Estimate)
February 27, 2014
Last Update Submitted That Met QC Criteria
February 26, 2014
Last Verified
February 1, 2014
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Urologic Diseases
- Congenital Abnormalities
- Genetic Diseases, Inborn
- Joint Diseases
- Musculoskeletal Diseases
- Muscular Diseases
- Musculoskeletal Abnormalities
- Abnormalities, Multiple
- Kidney Diseases, Cystic
- Ciliopathies
- Kidney Diseases
- Polycystic Kidney Diseases
- Polycystic Kidney, Autosomal Dominant
- Arthrogryposis
- Physiological Effects of Drugs
- Anti-Infective Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antifungal Agents
- Sirolimus
Other Study ID Numbers
- EK-1246
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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