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

NCT00346918 | Completed Phase 3 DMC

• 1 other identifier: EK-1246
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Keywords

ADPKD; autosomal dominant polycystic kidney disease; Sirolimus; volumetry

Outcome Measures

Primary Outcomes (1)

• renal volume measured by high resolution magnetic resolution imaging

  1.5 yrs

Secondary Outcomes (2)

• GFR

  1.5 yrs

• Adverse event

  1.5 yrs

Study Arms (2)

1

ACTIVE COMPARATOR

Treatment of hypertension, cyst infections and flank pain

Other: Standard

2

ACTIVE COMPARATOR

Sirolimus plus Standard Treatment

Drug: Sirolimus

Interventions

Sirolimus DRUG

Standard plus Sirolimus

Also known as: Rapamune (R)

2

Standard OTHER

Standard

Also known as: Treatment of hypertension, cyst infections and flank pain

1

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Zurich: lead

Study Sites (1)

University Hospital

Zurich, Canton of Zurich, 8091, Switzerland

Location

Related Publications (7)

• 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.

  PMID: 16221708 RESULT

• 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.

  PMID: 20581391 RESULT

• 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.

  PMID: 22417271 RESULT

• 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.

  PMID: 23071528 RESULT

• St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.

  PMID: 39356039 DERIVED

• 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.

  PMID: 19525519 DERIVED

• 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.

  PMID: 17868472 DERIVED

Related Links

• Homepage Study Center

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Polycystic Kidney Diseases; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Andreas L. Serra, MD

  University of Zurich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2006
• First Posted: June 30, 2006
• Study Start: June 1, 2006
• Primary Completion: January 1, 2010
• Study Completion: June 1, 2010
• Last Updated: February 27, 2014

Record last verified: 2014-02

Locations

CH (1)