Pulsed Oral Sirolimus in Autosomal Dominant Polycystic Kidney Disease

NCT ID: NCT02055079

Last Updated: 2018-10-31

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2019-12-31

Brief Summary

Sirolimus (SIR) has lead to a reduction of overall kidney size, a decrease in cyst density and general tubular cell proliferation in animal models, and to a reduction of the increase in creatinine and blood urea nitrogen by 34 and 39 percent respectively, as well as a reduction of cyst proliferation, expressed by a 30 percent reduction of overall kidney enlargement, a reduction in general cyst volume, and a reduction of the cyst volume density in the renal cortex in humans.

However, despite promising data from animal- and in vivo studies, most mammalian target of rapamycin inhibitor (mTOR-I) studies in patients with autosomal-dominant polycystic kidney disease (ADPKD) produced only subtle if any clinically relevant effects on cyst growth and the preservation of renal function.

In this study we will investigate if pulsed administration of SIR in a fixed weekly oral dose of 3 mg over 24 months compared to placebo significantly reduces cyst growth and preserves excretory renal function in patients with ADPKD and an estimated glomerular filtration (eGFR) rate below 60 mL/min per 1.73m2.

Conditions

Polycystic Kidney, Type 1 Autosomal Dominant Disease; Polycystic Kidney, Type 2 Autosomal Dominant Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Sirolimus

Fixed oral dose of 3 mg Sirolimus (blinded) once weekly for 24 months.

Group Type: EXPERIMENTAL

Sirolimus

Intervention Type: DRUG

Fixed oral dose of 3 mg sirolimus (blinded) once weekly for 24 months.

Placebo

Fixed oral dose of placebo (blinded) once weekly for 24 months.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Fixed oral dose of 3 mg placebo (blinded) once weekly for 24 months.

Interventions

Sirolimus

Fixed oral dose of 3 mg sirolimus (blinded) once weekly for 24 months.

Intervention Type: DRUG

Placebo

Fixed oral dose of 3 mg placebo (blinded) once weekly for 24 months.

Intervention Type: DRUG

Other Intervention Names

Rapamune

Eligibility Criteria

Inclusion Criteria

• ADPKD, as confirmed by history, ultrasound, computed- or magnetic resonance tomography
• Eighteen years of age, or older
• Baseline eGFR below 60 mL/min per 1.73m2
• Negative serum pregnancy test prior to administration of sirolimus and agreement to use contraception throughout the study and three months after
• Written informed consent

Exclusion Criteria

• Need for renal replacement therapy
• Pregnancy/lactation
• Plans to become pregnant in the near future
• Refusal to use sufficient contraception
• Proteinuria as defined as protein:creatinine ratio >1000 or >1g/d, respectively
• History of life threatening complications of ADPKD
• Evidence of active systemic- or localized major infection
• Evidence of infiltrate or consolidation on chest X-ray
• Use of any investigational drug or -treatment up to 4 weeks prior to enrolment and during the study
• Known allergy/hypersensitivity to sirolimus and its derivatives
• Medication that will interfere with the cytochrome P450 (CYP3A4/CYP3A5) system
• Total white blood cell count below or equal to 3000/mm3
• Platelet count below or equal to 100.000/mm3
• Fasting triglycerides above or equal to 400 mg/dL
• Fasting total cholesterol above or equal to 300 mg/dL
• Concomitant glomerular diseases
• Psychiatric disorders and any condition that might prevent full comprehension of the purposes and risks of the study
• History of malignancy, with the exception of adequately treated basal cell- and squamous cell carcinoma of the skin
• HIV positivity

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Markus Riegersperger, MD

Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Markus Riegersperger, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Gere Sunder-Plassmann, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Locations

Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna

Vienna, , Austria

Site Status: RECRUITING

Countries

Austria

Central Contacts

Markus Riegersperger, MD

Role: CONTACT

markus.riegersperger@gmail.com

0043140400 ext. 4391

Gere Sunder-Plassmann, MD

Role: CONTACT

gere.sunder-plassmann@meduniwien.ac.at

0043140400 ext. 4391

Facility Contacts

Markus Riegersperger, MD

Role: primary

markus.riegersperger@gmail.com

0043140400 ext. 4391

Gere Sunder-Plassmann, MD

Role: backup

gere.sunder-plassmann@meduniwien.ac.at

0043140400 ext. 4391

References

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.

Reference Type: DERIVED

PMID: 39356039 (View on PubMed)

Riegersperger M, Herkner H, Sunder-Plassmann G. Pulsed oral sirolimus in advanced autosomal-dominant polycystic kidney disease (Vienna RAP Study): study protocol for a randomized controlled trial. Trials. 2015 Apr 23;16:182. doi: 10.1186/s13063-015-0692-3.

Reference Type: DERIVED

PMID: 25899445 (View on PubMed)

Other Identifiers

2012-000550-60

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

15170

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

1060/2012

Identifier Type: OTHER

Identifier Source: secondary_id

V5.1/20.1.2013

Identifier Type: -

Identifier Source: org_study_id