Autosomal Dominant Polycystic Kidney Disease (ADPKD)Phase 3NCT00346918
Sirolimus (Rapamune®) for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
A Phase 3 study testing Sirolimus and Standard in people with Autosomal Dominant Polycystic Kidney Disease (ADPKD), run by University of Zurich at 1 site in Switzerland.
Trial summary
The aim of our study is to investigate whether Rapamune used at a low dose (2 mg/d) retards cyst growth and slows renal functional deterioration in patients with ADPKD. Read more about this study
- Who is it for?
- Ages 18 to 40 years
- Conditions the study is for
- Autosomal Dominant Polycystic Kidney Disease (ADPKD)
- What is being tested?
- Sirolimus and Standard
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jun 2006to Jun 2010
- Phase
- Phase 3
- 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 to 40 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male or female ADPKD patient between 18 and 40 years of age
- measured GFR higher than 70 ml/min 1.73m2
- documented kidney volume progression
- informed consent
Who cannot join
- Female of childbearing potential who is planning to become pregnant, who is pregnant and/or lactating, who is unwilling to use effective means of contraception
- increased liver enzymes (2-fold above normal values)
- hypercholesterolemia (fasting cholesterol > 8 mmol/l) or hypertriglyceridaemia (> 5 mmol/l) not controlled by lipid lowering therapy
- granulocytopenia (white blood cell < 3,000/mm3) or thrombocytopenia (platelets < 100,000/mm3),
- infection with hepatitis B or C, HIV
- any past or present malignancy
Show all 11Show fewer
- mental illness that interfere with the patient ability to comply with the protocol
- drug or alcohol abuse within one year of baseline
- co-medication with strong inhibitor of CYP3A4 and or P-gp like voriconazole, ketoconazole, diltiazem, verapamil, erythromycin
- co-medication with strong CYP3A4 and or P-gp inductor like rifampicin
- known hypersensitivity to macrolides or Rapamune
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Sirolimus (Rapamune®) for Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD): a Randomized Controlled Study.
The aim of our study is to investigate whether Rapamune used at a low dose (2 mg/d) retards cyst growth and slows renal functional deterioration in patients with ADPKD.
Read the detailed description
Currently there is no treatment for ADPKD other than supportive care and blood pressure control. Usually dialytic treatment or renal transplantation becomes necessary when the disease has progressed to end-stage renal failure.We and others could demonstrate that rapamycin, a classical mTOR inhibitor, retards cyst growth and preserves renal function in a rodent model of ADPKD. The aim of our study is to investigate whether Rapamune (2 mg/d) retards cyst growth and slows renal functional deterioration in patients with ADPKD. We anticipate that we can slow disease progression and delay the need for chronic renal replacement therapy by the inhibition of mTOR with Rapamune. This is a 24-month prospective, controlled, open label study with 2 parallel groups in patients with ADPKD. Patients will be randomized at a 1:1 ratio to one of the 2 treatment arms. Primary endpoint is percentage change of renal volume measured by high resolution magnetic resolution imaging.
- Being tested
- Sirolimus, Standard
- Keywords
- ADPKD, autosomal dominant polycystic kidney disease, Sirolimus, volumetry
- Medical subject headings
- Polycystic Kidney, Autosomal Dominant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamune (R)
Standard plus Sirolimus
StandardOther
Also called Treatment of hypertension, cyst infections and flank pain
Standard
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Treatment of hypertension, cyst infections and flank pain Receives: Other: Standard |
| 2 | Active comparator | Sirolimus plus Standard Treatment Receives: Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
renal volume measured by high resolution magnetic resolution imaging
Measured: 1.5 yrs
Secondary outcomes (2)
GFR
Measured: 1.5 yrs
Adverse event
Measured: 1.5 yrs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2006 (estimated)
- Study startJun 2006
- Primary completionJan 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Autosomal Dominant Polycystic Kidney Disease (ADPKD)Studies of the same condition, open and under way.
- More trials run by University of ZurichThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andreas L. Serra, MD, Principal investigator, University of Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00346918
- Sponsor's protocol ID
- EK-1246
- Status last verified
- Feb 2014
- First submitted
- 22 Jun 2006
- Last updated
- 27 Feb 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Wahl PR, Serra AL, Le Hir M, Molle KD, Hall MN, Wuthrich RP. Inhibition of mTOR with sirolimus slows disease progression in Han:SPRD rats with autosomal dominant polycystic kidney disease (ADPKD). Nephrol Dial Transplant. 2006 Mar;21(3):598-604. doi: 10.1093/ndt/gfi181. Epub 2005 Oct 12.
PubMed 16221708Serra AL, Poster D, Kistler AD, Krauer F, Raina S, Young J, Rentsch KM, Spanaus KS, Senn O, Kristanto P, Scheffel H, Weishaupt D, Wuthrich RP. Sirolimus and kidney growth in autosomal dominant polycystic kidney disease. N Engl J Med. 2010 Aug 26;363(9):820-9. doi: 10.1056/NEJMoa0907419. Epub 2010 Jun 26.
PubMed 20581391Braun M, Young J, Reiner CS, Poster D, Wuthrich RP, Serra AL. Ovarian toxicity from sirolimus. N Engl J Med. 2012 Mar 15;366(11):1062-4. doi: 10.1056/NEJMc1113145. No abstract available.
PubMed 22417271Braun M, Young J, Reiner CS, Poster D, Krauer F, Kistler AD, Kristanto P, Wang X, Liu Y, Loffing J, Andreisek G, von Eckardstein A, Senn O, Wuthrich RP, Serra AL. Low-dose oral sirolimus and the risk of menstrual-cycle disturbances and ovarian cysts: analysis of the randomized controlled SUISSE ADPKD trial. PLoS One. 2012;7(10):e45868. doi: 10.1371/journal.pone.0045868. Epub 2012 Oct 10.
PubMed 23071528St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
PubMed 39356039Serra AL, Kistler AD, Poster D, Krauer F, Senn O, Raina S, Pavik I, Rentsch K, Regeniter A, Weishaupt D, Wuthrich RP. Safety and tolerability of sirolimus treatment in patients with autosomal dominant polycystic kidney disease. Nephrol Dial Transplant. 2009 Nov;24(11):3334-42. doi: 10.1093/ndt/gfp280. Epub 2009 Jun 13.
PubMed 19525519Serra AL, Kistler AD, Poster D, Struker M, Wuthrich RP, Weishaupt D, Tschirch F. Clinical proof-of-concept trial to assess the therapeutic effect of sirolimus in patients with autosomal dominant polycystic kidney disease: SUISSE ADPKD study. BMC Nephrol. 2007 Sep 15;8:13. doi: 10.1186/1471-2369-8-13.
PubMed 17868472
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sirolimus (Rapamune®) for Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD): a Randomized Controlled Study.
- ClinicalTrials.gov ID
- NCT00346918
- Acronym / sponsor ID
- EK-1246
- Keywords
- ADPKD, autosomal dominant polycystic kidney disease, Sirolimus, volumetry
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Study start
- Jun 2006
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 30 Jun 2006 (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 aim of our study is to investigate whether Rapamune used at a low dose (2 mg/d) retards cyst growth and slows renal functional deterioration in patients with ADPKD.
Detailed description
Currently there is no treatment for ADPKD other than supportive care and blood pressure control. Usually dialytic treatment or renal transplantation becomes necessary when the disease has progressed to end-stage renal failure.We and others could demonstrate that rapamycin, a classical mTOR inhibitor, retards cyst growth and preserves renal function in a rodent model of ADPKD. The aim of our study is to investigate whether Rapamune (2 mg/d) retards cyst growth and slows renal functional deterioration in patients with ADPKD. We anticipate that we can slow disease progression and delay the need for chronic renal replacement therapy by the inhibition of mTOR with Rapamune. This is a 24-month prospective, controlled, open label study with 2 parallel groups in patients with ADPKD. Patients will be randomized at a 1:1 ratio to one of the 2 treatment arms. Primary endpoint is percentage change of renal volume measured by high resolution magnetic resolution imaging.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Other: StandardTreatment of hypertension, cyst infections and flank pain |
| 2 | Active comparator | Drug: SirolimusSirolimus plus Standard Treatment |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Male or female ADPKD patient between 18 and 40 years of age
- measured GFR higher than 70 ml/min 1.73m2
- documented kidney volume progression
- informed consent
Key exclusion criteria (11 listed)
- Female of childbearing potential who is planning to become pregnant, who is pregnant and/or lactating, who is unwilling to use effective means of contraception
- increased liver enzymes (2-fold above normal values)
- hypercholesterolemia (fasting cholesterol > 8 mmol/l) or hypertriglyceridaemia (> 5 mmol/l) not controlled by lipid lowering therapy
- granulocytopenia (white blood cell < 3,000/mm3) or thrombocytopenia (platelets < 100,000/mm3),
- infection with hepatitis B or C, HIV
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: Rapamune (R)Standard plus Sirolimus | Drug | 2 |
| StandardAlso: Treatment of hypertension, cyst infections and flank painStandard | Other | 1 |
Primary outcome
renal volume measured by high resolution magnetic resolution imaging
Time frame: 1.5 yrs
2 secondary outcomes
GFR
Time frame: 1.5 yrs
Adverse event
Time frame: 1.5 yrs
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 27 Feb 2014.
- Results publication: PubMed 16221708Wahl PR, Serra AL, Le Hir M, Molle KD, Hall MN, Wuthrich RP. Inhibition of mTOR with sirolimus slows disease progression in Han:SPRD rats with autosomal dominant polycystic kidney disease (ADPKD). Nephrol Dial Transplant. 2006 Mar;21(3):598-604. doi: 10.1093/ndt/gfi181. Epub 2005 Oct 12.
- Results publication: PubMed 20581391Serra AL, Poster D, Kistler AD, Krauer F, Raina S, Young J, Rentsch KM, Spanaus KS, Senn O, Kristanto P, Scheffel H, Weishaupt D, Wuthrich RP. Sirolimus and kidney growth in autosomal dominant polycystic kidney disease. N Engl J Med. 2010 Aug 26;363(9):820-9. doi: 10.1056/NEJMoa0907419. Epub 2010 Jun 26.
- Results publication: PubMed 22417271Braun M, Young J, Reiner CS, Poster D, Wuthrich RP, Serra AL. Ovarian toxicity from sirolimus. N Engl J Med. 2012 Mar 15;366(11):1062-4. doi: 10.1056/NEJMc1113145. No abstract available.
- Results publication: PubMed 23071528Braun M, Young J, Reiner CS, Poster D, Krauer F, Kistler AD, Kristanto P, Wang X, Liu Y, Loffing J, Andreisek G, von Eckardstein A, Senn O, Wuthrich RP, Serra AL. Low-dose oral sirolimus and the risk of menstrual-cycle disturbances and ovarian cysts: analysis of the randomized controlled SUISSE ADPKD trial. PLoS One. 2012;7(10):e45868. doi: 10.1371/journal.pone.0045868. Epub 2012 Oct 10.
- Derived from this study: PubMed 39356039St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
- Derived from this study: PubMed 19525519Serra AL, Kistler AD, Poster D, Krauer F, Senn O, Raina S, Pavik I, Rentsch K, Regeniter A, Weishaupt D, Wuthrich RP. Safety and tolerability of sirolimus treatment in patients with autosomal dominant polycystic kidney disease. Nephrol Dial Transplant. 2009 Nov;24(11):3334-42. doi: 10.1093/ndt/gfp280. Epub 2009 Jun 13.
- Derived from this study: PubMed 17868472Serra AL, Kistler AD, Poster D, Struker M, Wuthrich RP, Weishaupt D, Tschirch F. Clinical proof-of-concept trial to assess the therapeutic effect of sirolimus in patients with autosomal dominant polycystic kidney disease: SUISSE ADPKD study. BMC Nephrol. 2007 Sep 15;8:13. doi: 10.1186/1471-2369-8-13.
- Homepage Study CenterLink provided by the sponsor.
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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.
Andreas L. Serra, MD principal investigator
University of Zurich
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sirolimus and Standard in people with Autosomal Dominant Polycystic Kidney Disease (ADPKD), run by University of Zurich at 1 site in Switzerland.
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 4 inclusion and 11 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 27 Feb 2014. 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 Switzerland. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
renal volume measured by high resolution magnetic resolution imaging (time frame: 1.5 yrs). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00346918, which also lists 7 linked publications.
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 27 Feb 2014.