Pulsed Oral Sirolimus in Autosomal Dominant Polycystic Kidney Disease (RAP)
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| ClinicalTrials.gov Identifier: NCT02055079 |
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Recruitment Status :
Recruiting
First Posted : February 4, 2014
Last Update Posted : October 31, 2018
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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 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 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Sirolimus
Fixed oral dose of 3 mg Sirolimus (blinded) once weekly for 24 months.
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Drug: Sirolimus
Fixed oral dose of 3 mg sirolimus (blinded) once weekly for 24 months.
Other Name: Rapamune |
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Placebo Comparator: Placebo
Fixed oral dose of placebo (blinded) once weekly for 24 months.
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Drug: Placebo
Fixed oral dose of 3 mg placebo (blinded) once weekly for 24 months. |
- 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.
- 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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
| 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 |
| 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 | |
| Principal Investigator: | Markus Riegersperger, MD | Medical University of Vienna | |
| Principal Investigator: | Gere Sunder-Plassmann, MD | Medical University of Vienna |
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 Posted: | February 4, 2014 Key Record Dates |
| Last Update Posted: | October 31, 2018 |
| Last Verified: | October 2018 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
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ADPKD PKD Polycystic kidney disease |
Mammalian target of rapamycin mTOR-I Sirolimus |
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Kidney Diseases Polycystic Kidney Diseases Polycystic Kidney, Autosomal Dominant Urologic Diseases Kidney Diseases, Cystic Abnormalities, Multiple Congenital Abnormalities Ciliopathies 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 |