Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01632605
Other study ID # 003/2008/1.0
Secondary ID
Status Completed
Phase N/A
First received May 13, 2012
Last updated June 28, 2012
Start date November 2009
Est. completion date April 2012

Study information

Verified date June 2012
Source Medical University of Vienna
Contact n/a
Is FDA regulated No
Health authority Austria: Agency for Health and Food SafetyAustria: EthikkommissionEuropean Union: European Medicines Agency
Study type Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety of a daily single oral dose of sirolimus in patients with advanced autosomal dominant polycystic kidney disease.


Description:

Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of renal cystic diseases, affecting all ethnic groups with an incidence of 1 in 400 to 1.000. In Austria an estimated 8.000 to 21.000 people, and an estimated 670.000 to 1.675.000 people worldwide are affected by ADPKD, although statements of up to 6.000.000 affected individuals have been made. ADPKD is responsible for 5 to 10 percent of patients on chronic hemodialysis. Individuals with ADPKD usually present in the 3rd to 4th decade of life, progressing to end-stage renal disease within 5 to 10 years after the onset of renal insufficiency. Usually renal replacement therapy, either by chronic dialysis or renal transplantation, becomes necessary. Currently there is no treatment for ADPKD other than blood pressure control and supportive care.

Thus, novel therapies for ADPKD are of great importance.

The formation of cysts in ADPKD follows a mutation located within either the polycystic kidney disease 1 or -2 gene on chromosomes 16 and 4, which are coding for polycystin 1 (PC1) and -2 (PC2), respectively. PC1 and PC2 are members of the polycystin family of integral membrane proteins. PC1 acts as a G-protein coupled receptor and is suggested to mediate cell-cell and cell-matrix interactions. PC2 acts as a nonselective cation channel and is supposed to act in ion exchange mechanisms. Among other pathways PC1 and 2 are functioning via a mammalian target of rapamycin (mTOR) pathway, which is essential in protein translation, cell proliferation and -growth. Inhibition of the mTOR-pathway has reduced kidney enlargement in rodent polycystic kidney disease models and has shown to reduce the volume of cysts in human polycystic kidney- and polycystic liver disease. Thus, we hypothesize that the mTOR inhibitor sirolimus, an immunosuppressant drug with strong anti-proliferative effects, will delay the progression of renal insufficiency in patients with ADPKD in advanced stages of the disease.

Before conducting a large multicenter randomized controlled trial in this population we will demonstrate that therapy with mTOR-I does not accelerate the decline in renal function (as natural course of the disease), as well as mTOR-I does not aggravate prevalent-, or cause new onset of proteinuria, as expressed by the protein/creatinine ratio, in patients with ADPKD and an eGFR between 20 and 40 mL/min per 1.73sqm, compared to a historic cohort of patients with ADPKD and an eGFR between 20 and 40 mL/min per 1.73sqm, treated at the Department of Medicine III, Division of Nephrology and Dialysis, Medical University Vienna.


Recruitment information / eligibility

Status Completed
Enrollment 8
Est. completion date April 2012
Est. primary completion date April 2012
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility Inclusion Criteria:

- ADPKD

- Eighteen years of age, or older.

- Baseline eGFR of 20-40mL/min per 1.73m2.

- Negative serum pregnancy test prior to administration of sirolimus and agreement to use contraception throughout the pilot safety study and three months after. Any participant who is getting pregnant during the pilot safety study period will have to discontinue.

- Written informed consent.

Exclusion Criteria:

- Pregnancy or lactation or plans to become pregnant in the near future or disagreement to use contraception.

- History of life threatening complications of ADPKD.

- Evidence of active systemic- or localized major infection.

- Evidence of infiltrate, cavities or consolidation on chest X-ray.

- Use of any investigational drug or -treatment up to 4 weeks prior to the enrolment and during the pilot safety study.

- Known hypersensitivity to sirolimus and its derivatives.

- Treatment with substances known to interfere with the cytochrome p-450 (CYP) 3A4/3A5 systems.

- Screening/baseline total white blood cell count below or equal to 3000/mm3.

- Screening/baseline platelet count below or equal to 100.000/mm3.

- Screening/baseline fasting triglycerides above or equal to 400 mg/dL.

- Screening/baseline fasting total cholesterol above or equal to 300 mg/dL.

- Concomitant glomerular diseases.

- Psychiatric disorders or any condition that might prevent the full comprehension of the purposes and risks of the pilot safety study.

- History of malignancies with the exception of adequately treated basal- and squamous-cell carcinomas of the skin.

- HIV infection.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label


Related Conditions & MeSH terms


Intervention

Drug:
Sirolimus
Coated tablets, 1mg and 2mg available. Daily oral single dose with trough levels of 4-8ng/mL. Total intake for 6 months.

Locations

Country Name City State
Austria Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna Vienna

Sponsors (1)

Lead Sponsor Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type Measure Description Time frame Safety issue
Primary Slope in estimated glomerular filtration rate (eGFR; 4 variables MDRD equation) and proteinuria within six months of exposure to sirolimus. A single daily oral dose of sirolimus with trough levels of 4 to 8ng/dL in patients with advanced polycystic kidney disease and an eGFR of 20-40mL/min per 1.73m2 does not lead to a greater decline in kidney function as represented by the eGFR than -8.8mL/min per 1.73m2 within 6 months (one-sided) as well as it does not lead to an incline in proteinuria, as represented by the logarithm of the protein-creatinine ratio, greater than 0.39 within 6 months (one-sided). Six months Yes
Secondary Leucopenia Drop in WBC below 4 G/L 6 months Yes
Secondary Thrombopenia Drop in platelets below 150 G/L 6 months Yes
Secondary Aphthae New onset of aphthaeous stomatitis under therapy with sirolimus 6 months Yes
Secondary Dysfunctional wound healing Dysfunctional and/or prolonged wound healing attributed to sirolimus therapy 6 months Yes
Secondary Pneumonitis Persisting cough and infiltrates on chest x-ray 6 months Yes
Secondary Acne Acne attributed to sirolimus therapy 6 months Yes
See also
  Status Clinical Trial Phase
Recruiting NCT04310319 - Wishing to Decrease Aquaresis in ADPKD Patients Treated With a V2Ra; the Effect of Regulating Protein and Salt N/A
Completed NCT02776241 - Effect of Water Intake and Water Restriction on Total Kidney Volume in Autosomal Dominant Polycystic Kidney Disease N/A
Terminated NCT04152837 - Safety of Lixivaptan in Subjects Previously Treated With Tolvaptan for Autosomal Dominant Polycystic Kidney Disease Phase 3
Completed NCT03717883 - ADPKD Alterations in Hepatic Transporter Function
Recruiting NCT05014178 - Kidney Sodium Functional Imaging
Recruiting NCT05521191 - A Study of RGLS8429 in Patients With Autosomal Dominant Polycystic Kidney Disease Phase 1
Terminated NCT04064346 - Efficacy and Safety of Lixivaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease Phase 3
Completed NCT03203642 - Study of the Efficacy and Safety of Tesevatinib in Subjects With ADPKD Phase 2
Recruiting NCT04338048 - Autosomal Dominant Polycystic Kidney Disease (ADPKD) Study
Not yet recruiting NCT06100133 - Treat Autosomal Dominant Polycystic Kidney Disease With Oral Ketone Ester? Phase 2
Terminated NCT03918447 - A Trial of Bardoxolone Methyl in Patients With ADPKD - FALCON Phase 3
Recruiting NCT06416761 - Genetics in the Progression of Nephropathies
Not yet recruiting NCT05373264 - HYDROchlorothiazide to PROTECT Polycystic Kidney Disease Patients and Improve Their Quality of Life Phase 3
Recruiting NCT06085807 - Genetic Testing in Autosomal Dominant Polycystic Kidney Disease
Completed NCT01853553 - Mineralocorticoid Antagonism and Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney Disease (ADPKD) Phase 3
Completed NCT04472624 - Short Term Induction of Ketosis in PKD N/A
Not yet recruiting NCT03764605 - Metformin vs Tolvaptan for Treatment of Autosomal Dominant Polycystic Kidney Disease Phase 3
Completed NCT04680780 - Ketogenic Dietary Interventions in Autosomal Dominant Polycystic Kidney Disease (ADPKD) N/A
Completed NCT02161068 - Clinical Care of Autosomal Polycystic Kidney Disease: Retrospective Analysis and Prospective PKD Genotyping
Active, not recruiting NCT03273413 - Statin Therapy in Patients With Early Stage ADPKD Phase 4