Back to resultsSirolimus (Rapamune®) for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Primary Purpose
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Status
Completed
Phase
Phase 3
Locations
Switzerland
Study Type
Interventional
Intervention
Sirolimus
Standard
Sponsored by
About this trial
This is an interventional treatment trial for Autosomal Dominant Polycystic Kidney Disease (ADPKD) focused on measuring ADPKD, autosomal dominant polycystic kidney disease, Sirolimus, volumetry
Eligibility Criteria
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
Sites / Locations
- University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
1
2
Arm Description
Treatment of hypertension, cyst infections and flank pain
Sirolimus plus Standard Treatment
Outcomes
Primary Outcome Measures
renal volume measured by high resolution magnetic resolution imaging
Secondary Outcome Measures
GFR
Adverse event
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00346918
Brief Title
Sirolimus (Rapamune®) for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Official Title
Sirolimus (Rapamune®) for Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD): a Randomized Controlled Study.
Study Type
Interventional
2. Study Status
Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
June 2006 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
June 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Zurich
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Keywords
ADPKD, autosomal dominant polycystic kidney disease, Sirolimus, volumetry
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Description
Treatment of hypertension, cyst infections and flank pain
Arm Title
2
Arm Type
Active Comparator
Arm Description
Sirolimus plus Standard Treatment
Intervention Type
Drug
Intervention Name(s)
Sirolimus
Other Intervention Name(s)
Rapamune (R)
Intervention Description
Standard plus Sirolimus
Intervention Type
Other
Intervention Name(s)
Standard
Other Intervention Name(s)
Treatment of hypertension, cyst infections and flank pain
Intervention Description
Standard
Primary Outcome Measure Information:
Title
renal volume measured by high resolution magnetic resolution imaging
Time Frame
1.5 yrs
Secondary Outcome Measure Information:
Title
GFR
Time Frame
1.5 yrs
Title
Adverse event
Time Frame
1.5 yrs
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andreas L. Serra, MD
Organizational Affiliation
University of Zurich
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital
City
Zurich
ZIP/Postal Code
8091
Country
Switzerland
12. IPD Sharing Statement
Citations:
PubMed Identifier
16221708
Citation
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.
Results Reference
result
PubMed Identifier
20581391
Citation
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.
Results Reference
result
PubMed Identifier
22417271
Citation
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.
Results Reference
result
PubMed Identifier
23071528
Citation
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.
Results Reference
result
PubMed Identifier
19525519
Citation
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.
Results Reference
derived
PubMed Identifier
17868472
Citation
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.
Results Reference
derived
Links:
URL
http://www.zystennieren.ch
Description
Homepage Study Center
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Sirolimus (Rapamune®) for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
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