ADPKDRAPNCT01632605
The Vienna RAP Pilot Study
A study testing Sirolimus in people with ADPKD, run by Medical University of Vienna at 1 site in Austria.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ADPKD
- What is being tested?
- Sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteAustria
- Study dates
- Nov 2009to Apr 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 15Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Austria1 site
Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna
Vienna, State of Vienna, 1090
About this study
Official title: Rapamycin in Advanced Polycystic Kidney Disease Pilot Study
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.
Read the detailed 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.
- Conditions
- ADPKD
- Being tested
- Sirolimus
- Keywords
- ADPKD, Autosomal dominant polycystic kidney disease, Sirolimus, Rapamune, Polycystic liver disease, Rapamycin, Mammalian target of rapamycin, m-TOR, m-TOR inhibition
- Medical subject headings
- Polycystic Kidney, Autosomal Dominant, Polycystic liver disease, Hereditary Sensory and Autonomic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called RAPAMUNE
Coated tablets, 1mg and 2mg available. Daily oral single dose with trough levels of 4-8ng/mL. Total intake for 6 months.
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus | Experimental | Daily single oral dose of 1-3mg sirolimus with an initial loading dose of 6mg. Receives: Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Six months
Secondary outcomes (6)
Leucopenia
Drop in WBC below 4 G/L
Measured: 6 months
Thrombopenia
Drop in platelets below 150 G/L
Measured: 6 months
Aphthae
New onset of aphthaeous stomatitis under therapy with sirolimus
Measured: 6 months
Dysfunctional wound healing
Dysfunctional and/or prolonged wound healing attributed to sirolimus therapy
Measured: 6 months
Pneumonitis
Persisting cough and infiltrates on chest x-ray
Measured: 6 months
Acne
Acne attributed to sirolimus therapy
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2012 (estimated)
- Study startNov 2009
- Primary completionApr 2012
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ADPKDStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gere Sunder-Plassmann, Medical University of Vienna
- Investigators
- Gere Sunder-Plassmann, MD, Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01632605
- Sponsor's protocol ID
- 003/2008/1.0
- Acronym
- RAP
- Status last verified
- Jun 2012
- First submitted
- 13 May 2012
- Last updated
- 3 Jul 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rapamycin in Advanced Polycystic Kidney Disease Pilot Study
- ClinicalTrials.gov ID
- NCT01632605
- Acronym / sponsor ID
- RAP / 003/2008/1.0
- Conditions
- ADPKD
- Keywords
- ADPKD, Autosomal dominant polycystic kidney disease, Sirolimus, Rapamune, Polycystic liver disease, Rapamycin, Mammalian target of rapamycin, m-TOR
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- Nov 2009
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 3 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sirolimus | Experimental | Drug: SirolimusDaily single oral dose of 1-3mg sirolimus with an initial loading dose of 6mg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SirolimusAlso: RAPAMUNECoated tablets, 1mg and 2mg available. Daily oral single dose with trough levels of 4-8ng/mL. Total intake for 6 months. | Drug | Sirolimus |
Primary outcome
Slope in estimated glomerular filtration rate (eGFR; 4 variables MDRD equation) and proteinuria within six months of exposure to sirolimus.
Time frame: Six months
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).
6 secondary outcomes
Leucopenia
Time frame: 6 months
Thrombopenia
Time frame: 6 months
Aphthae
Time frame: 6 months
Dysfunctional wound healing
Time frame: 6 months
Pneumonitis
Time frame: 6 months
Acne
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2012.
Related trials for ADPKD
Active, not recruitingObservational study
Polycystic Kidney Disease 1 (PKD1) Gene Variant Groups in Autosomal Dominant Polycystic Kidney Disease
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GBP-213 in Patients With Autosomal Dominant Polycystic Kidney Disease
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Safety, Tolerability and Pharmacokinetics of AZD1613 in Adults With Autosomal Dominant Polycystic Kidney Disease
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Absorption, Distribution, Metabolism, and Excretion of 14C-VX-407 After a Single Oral Dose
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ANCHOR Study: A Study to Assess the Safety and Efficacy of ABBV-CLS-628 in Adult Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Autosomal Dominant Polycystic Kidney Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gere Sunder-Plassmann, MD principal investigator
Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sirolimus in people with ADPKD, run by Medical University of Vienna at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Slope in estimated glomerular filtration rate (eGFR; 4 variables MDRD equation) and proteinuria within six months of exposure to sirolimus. (time frame: Six months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2012.