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

This study is currently recruiting participants.
Verified April 2014 by Markus Riegersperger, MD, Medical University of Vienna
Sponsor:
ClinicalTrials.gov Identifier:
NCT02055079
First Posted: February 4, 2014
Last Update Posted: April 9, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Markus Riegersperger, MD, Medical University of Vienna
  Purpose

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 Intervention Phase
Polycystic Kidney, Type 1 Autosomal Dominant Disease Polycystic Kidney, Type 2 Autosomal Dominant Disease Drug: Sirolimus Drug: Placebo Phase 3

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Markus Riegersperger, MD, Medical University of Vienna:

Primary Outcome Measures:
  • 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:
  • 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.


Estimated Enrollment: 68
Study Start Date: April 2014
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02055079


Contacts
Contact: Markus Riegersperger, MD 0043140400 ext 4391 markus.riegersperger@meduniwien.ac.at
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@meduniwien.ac.at   
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):
Responsible Party: Markus Riegersperger, MD, Dr., Medical University of Vienna
ClinicalTrials.gov Identifier: NCT02055079     History of Changes
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 Submitted: January 31, 2014
First Posted: February 4, 2014
Last Update Posted: April 9, 2014
Last Verified: April 2014

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:
Polycystic Kidney Diseases
Polycystic Kidney, Autosomal Dominant
Kidney Diseases
Urologic Diseases
Kidney Diseases, Cystic
Abnormalities, Multiple
Congenital Abnormalities
Genetic Diseases, Inborn
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs