Sirolimus (Rapamune®) for Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Autosomal Dominant Polycystic Kidney Disease (ADPKD) Clinical Trial

Official title:

Sirolimus (Rapamune®) for Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD): a Randomized Controlled Study.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00346918
• Other study ID #: EK-1246
• Status: Completed
• Phase: Phase 3
• First received: June 22, 2006
• Last updated: February 26, 2014
• Start date: June 2006
• Est. completion date: June 2010

Study information

• Verified date: February 2014
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: June 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 40 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Autosomal Dominant Polycystic Kidney Disease (ADPKD)
• Kidney Diseases
• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Intervention

Drug:
• Sirolimus
Standard plus Sirolimus

Other:
• Standard
Standard

Locations

Country	Name	City	State
Switzerland	University Hospital	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
University of Zurich

Country where clinical trial is conducted

Switzerland, 

References & Publications (4)

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: anal — View Citation

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. — View 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, Wüthrich RP. Sirolimus and kidney growth in autosomal dominant polycystic kidney disease. N Engl J Med. 2010 Aug 26;363(9):82 — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	renal volume measured by high resolution magnetic resolution imaging		1.5 yrs	No
Secondary	GFR		1.5 yrs	Yes
Secondary	Adverse event		1.5 yrs	Yes

External Links

•   Homepage Study Center