Sirolimus (Rapamune®) for Autosomal Dominant Polycystic Kidney Disease (ADPKD) - Full Text View

Purpose

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.

Condition	Intervention	Phase
Autosomal Dominant Polycystic Kidney Disease (ADPKD)	Drug: Sirolimus Other: Standard	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Sirolimus (Rapamune®) for Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD): a Randomized Controlled Study.

Resource links provided by NLM:

Genetics Home Reference related topics: polycystic kidney disease

MedlinePlus related topics: High Blood Pressure Kidney Diseases

Drug Information available for: Sirolimus Everolimus Temsirolimus

U.S. FDA Resources

Further study details as provided by University of Zurich:

Primary Outcome Measures:

renal volume measured by high resolution magnetic resolution imaging [ Time Frame: 1.5 yrs ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

GFR [ Time Frame: 1.5 yrs ] [ Designated as safety issue: Yes ]
Adverse event [ Time Frame: 1.5 yrs ] [ Designated as safety issue: Yes ]


Enrollment:	100
Study Start Date:	June 2006
Study Completion Date:	June 2010
Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Treatment of hypertension, cyst infections and flank pain	Other: Standard Standard Other Name: Treatment of hypertension, cyst infections and flank pain
Active Comparator: 2 Sirolimus plus Standard Treatment	Drug: Sirolimus Standard plus Sirolimus Other Name: Rapamune (R)

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.

Eligibility


Ages Eligible for Study:	18 Years to 40 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00346918

Locations


Switzerland
University Hospital
Zurich, Switzerland, 8091

Sponsors and Collaborators

University of Zurich

Investigators


Principal Investigator:	Andreas L. Serra, MD	University of Zurich

More Information

Additional Information:

Homepage Clinic for Nephrology, University Hospital Zurich This link exits the ClinicalTrials.gov site

Homepage Study Center This link exits the ClinicalTrials.gov site

Publications:

Wahl PR, Serra AL, Le Hir M, Molle KD, Hall MN, Wüthrich 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. 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, Wüthrich 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, Wüthrich RP, Serra AL. Ovarian toxicity from sirolimus. N Engl J Med. 2012 Mar 15;366(11):1062-4. doi: 10.1056/NEJMc1113145.

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, Wüthrich 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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Serra AL, Kistler AD, Poster D, Krauer F, Senn O, Raina S, Pavik I, Rentsch K, Regeniter A, Weishaupt D, Wüthrich 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, Wüthrich 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.


Responsible Party:	University of Zurich
ClinicalTrials.gov Identifier:	NCT00346918 History of Changes
Other Study ID Numbers:	EK-1246
Study First Received:	June 22, 2006
Last Updated:	February 26, 2014
Health Authority:	Switzerland: Swissmedic

Keywords provided by University of Zurich:


ADPKD autosomal dominant polycystic kidney disease Sirolimus volumetry

Additional relevant MeSH terms:


Kidney Diseases Multicystic Dysplastic Kidney Polycystic Kidney Diseases Polycystic Kidney, Autosomal Dominant Congenital Abnormalities Kidney Diseases, Cystic Urogenital Abnormalities Urologic Diseases Everolimus Sirolimus	Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Antifungal Agents Antineoplastic Agents Immunologic Factors Immunosuppressive Agents Pharmacologic Actions Physiological Effects of Drugs Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015