Pulsed Oral Sirolimus in Autosomal Dominant Polycystic Kidney Disease (RAP)

• ClinicalTrials.gov Identifier: NCT02055079
• Recruitment Status: Unknown
• First Posted: February 4, 2014
• Last Update Posted: October 31, 2018
• Sponsor: Medical University of Vienna
• Information provided by (Responsible Party): Markus Riegersperger, MD, Medical University of Vienna

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Polycystic Kidney, Type 1 Autosomal Dominant Disease; Polycystic Kidney, Type 2 Autosomal Dominant Disease	Drug: Sirolimus; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 68 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Pulsed Oral Sirolimus in Autosomal Dominant Polycystic Kidney Disease - The Vienna RAP Study
• Study Start Date: April 2014
• Estimated Primary Completion Date: April 2019
• Estimated Study Completion Date: December 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Sirolimus; Fixed oral dose of 3 mg Sirolimus (blinded) once weekly for 24 months.	Drug: Sirolimus; Fixed oral dose of 3 mg sirolimus (blinded) once weekly for 24 months.; Other Name: Rapamune
Placebo Comparator: Placebo; Fixed oral dose of placebo (blinded) once weekly for 24 months.	Drug: Placebo; Fixed oral dose of 3 mg placebo (blinded) once weekly for 24 months.

Outcome Measures

Primary Outcome Measures :

1. Change in kidney function from baseline to month 24 [ Time Frame: Baseline, 24 months ]
   Fifty percent reduction in doubling of serum creatinine, or initiation of dialysis over a period of two years. Less or equal than 1.5 fold increase in serum creatinine without initiation of dialysis over two years is considered a beneficial outcome, increases in serum creatinine greater than 1.5 over two years or initiation of dialysis are considered a non-beneficial outcome.

Secondary Outcome Measures :

1. Change of safety parameters from baseline to month 24 [ Time Frame: Baseline, 24 months ]
   Safety, change in proteinuria, as indicated by albumin/creatinine- and protein/creatinine ratio, respectively.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Markus Riegersperger, MD; 0043140400 ext 4391; markus.riegersperger@gmail.com

Contact: Gere Sunder-Plassmann, MD; 0043140400 ext 4391; gere.sunder-plassmann@meduniwien.ac.at

Locations

Austria

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

Vienna, Austria, 1090

Contact: Markus Riegersperger, MD 0043140400 ext 4391 markus.riegersperger@gmail.com

Contact: Gere Sunder-Plassmann, MD 0043140400 ext 4391 gere.sunder-plassmann@meduniwien.ac.at

Principal Investigator: Markus Riegersperger, MD

Sub-Investigator: Gere Sunder-Plassmann, MD

Sponsors and Collaborators

Medical University of Vienna

Investigators

• Principal Investigator: Markus Riegersperger, MD; Medical University of Vienna
• Principal Investigator: Gere Sunder-Plassmann, MD; Medical University of Vienna

More Information

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

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.

• Responsible Party: Markus Riegersperger, MD, Dr., Medical University of Vienna
• ClinicalTrials.gov Identifier: NCT02055079
• Other Study ID Numbers: V5.1/20.1.2013; 2012-000550-60 ( EudraCT Number ); 15170 ( Other Grant/Funding Number: Oesterreichische Nationalbank ); 1060/2012 ( Other Identifier: Ethics committee Medical University of Vienna )
• First Posted: February 4, 2014
• Last Update Posted: October 31, 2018
• Last Verified: October 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Markus Riegersperger, MD, Medical University of Vienna:

ADPKD; PKD; Polycystic kidney disease; Mammalian target of rapamycin; mTOR-I; Sirolimus

Additional relevant MeSH terms:

Arthrogryposis; Kidney Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Urologic Diseases; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Musculoskeletal Abnormalities; Congenital Abnormalities; Kidney Diseases, Cystic; Abnormalities, Multiple; Ciliopathies; Genetic Diseases, Inborn; Sirolimus; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Antifungal Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs