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

Sponsored by:	University of Zurich
Information provided by:	University of Zurich
ClinicalTrials.gov Identifier:	NCT00346918

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 III

Genetics Home Reference related topics: polycystic kidney disease

Drug Information available for: Sirolimus

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Single Blind (Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study
Official Title:	Sirolimus (Rapamune®) for Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD): a Randomized Controlled Study.

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 ]

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

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

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

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

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 of Results:

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. Epub 2005 Oct 12.

Publications indexed to this study:

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.

Responsible Party:	University Hospital Zurich ( Andreas L. Serra, MD )
Study ID Numbers:	EK-1246
Study First Received:	June 22, 2006
Last Updated:	November 25, 2008
ClinicalTrials.gov Identifier:	NCT00346918
Health Authority:	Switzerland: Swissmedic

Keywords provided by University of Zurich:

ADPKD
autosomal dominant polycystic kidney disease
Sirolimus
volumetry

Study placed in the following topic categories:

Sirolimus
Urologic Diseases
Clotrimazole
Polycystic Kidney, Autosomal Dominant
Miconazole

Kidney Diseases, Cystic
Tioconazole
Polycystic Kidney Diseases
Kidney Diseases

Additional relevant MeSH terms:

Anti-Bacterial Agents
Anti-Infective Agents
Immunologic Factors
Antineoplastic Agents
Antifungal Agents

Therapeutic Uses
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Immunosuppressive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009