Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD): The Role of Biomarkers in Predicting a Response to Therapy

• ClinicalTrials.gov Identifier: NCT00920309
• Recruitment Status: Terminated
• First Posted: June 15, 2009
• Results First Posted: April 14, 2014
• Last Update Posted: April 14, 2014
• Sponsor: Yale University
• Information provided by (Responsible Party): Yale University

Tracking Information

• First Submitted Date: June 12, 2009
• First Posted Date: June 15, 2009
• Results First Submitted Date: August 29, 2013
• Results First Posted Date: April 14, 2014
• Last Update Posted Date: April 14, 2014
• Study Start Date: June 2009
• Actual Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 7, 2014): Total Kidney Volume (mL) [ Time Frame: 2 years ]
• Original Primary Outcome Measures (submitted: June 12, 2009): combined kidney volume [ Time Frame: 2 years ]
• Current Secondary Outcome Measures (submitted: March 7, 2014): Glomerular Filtration Rate (Kidney Function) [ Time Frame: 2 years ]

Original Secondary Outcome Measures (submitted: June 12, 2009)

• kidney function [ Time Frame: 2 years ]
• change in biomarkers [ Time Frame: 2 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD): The Role of Biomarkers in Predicting a Response to Therapy
• Official Title: Rapamycin as Treatment for ADPKD: The Role of Biomarkers in Predicting a Response to Therapy

Brief Summary

Currently the only approved use for rapamycin (sirolimus) is for immunosuppression after renal transplantation.

This trial is designed to determine whether rapamycin is safe and effective treatment for patients with polycystic kidney disease (ADPKD). Patients will be followed by volumetric magnetic resonance imaging (MRI) to observe for change in kidney (and cyst) size. Blood and urine samples will also be collected to evaluate for change in biomarkers with treatment.

• Detailed Description: This is a 2 year, open label trial to evaluate the role of rapamycin as treatment for ADPKD. Patients will be randomized 2:1 to the rapamycin arm or to standard therapy. The dose of rapamycin will be adjusted so that patients obtain 24 trough levels of 4-6ng/ml. There will be a volumetric MRI measurement at the start and end of the treatment period. Patients will be monitored every 4 months throughout the study.
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Autosomal Dominant Polycystic Kidney Disease

Intervention

• Drug: Rapamycin
  The starting dose of rapamycin will be 1 mg daily. The dose will be increased as needed to achieve a 24 hour trough level of 4-6 ng/ml.
  Other Name: sirolimus
• Other: Standard of Care-Placebo

Study Arms

• Experimental: Rapamycin

  Drug: Rapamycin

  Other Names:

  sirolimus The starting dose of rapamycin will be 1 mg daily. The dose will be increased as needed to achieve a 24 hour trough level of 4-6 ng/ml.

  Intervention: Drug: Rapamycin
• Placebo Comparator: Standard of Care-Placebo
  Standard of Care
  Intervention: Other: Standard of Care-Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 7, 2014): 21
• Original Estimated Enrollment (submitted: June 12, 2009): 45
• Actual Study Completion Date: July 2010
• Actual Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• adult ADPKD patients aged 18-70
• combined kidney volume >1200 ml
• estimated creatinine clearance >60 ml/min
• absence of implanted ferromagnetic objects

Exclusion Criteria:

• Age >70
• uncontrolled hyperlipidemia
• Proteinuria >500 mg/day
• unstable cerebral aneurysm
• active coronary artery disease
• diagnosis of another systemic condition affecting kidney function (ie: diabetes, hepatitis B or C, HIV)
• diagnosis of cancer other than skin cancer
• pregnancy or lactation
• presence of implanted ferromagnetic objects

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00920309
• Other Study ID Numbers: HIC#0903004934
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Yale University
• Study Sponsor: Yale University
• Collaborators: Not Provided

Investigators

• Principal Investigator: Neera K Dahl, MD, PhD; Yale University

• PRS Account: Yale University
• Verification Date: March 2014