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Trial record 1 of 1 for:    NCT00286156
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Pilot Study of Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD)

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ClinicalTrials.gov Identifier: NCT00286156
Recruitment Status : Completed
First Posted : February 3, 2006
Results First Posted : April 6, 2015
Last Update Posted : April 6, 2015
Sponsor:
Collaborator:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
The Cleveland Clinic

Tracking Information
First Submitted Date  ICMJE February 1, 2006
First Posted Date  ICMJE February 3, 2006
Results First Submitted Date  ICMJE March 31, 2015
Results First Posted Date  ICMJE April 6, 2015
Last Update Posted Date April 6, 2015
Study Start Date  ICMJE October 2006
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 31, 2015)
Change in GFR From Baseline to 12 Months [ Time Frame: From baseline to 12 months ]
GFR (glomerular filtration rate) was measured by iothalamate. GFR is a key indicator of renal function.
Original Primary Outcome Measures  ICMJE
 (submitted: February 1, 2006)
Change in Iothalamate GFR from baseline to 12 months
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 31, 2015)
Change in Total Kidney Volume as Measured by 3D-CT From Baseline to 12 Months [ Time Frame: From baseline to 12 months ]
Total kidney volume measured by CT from baseline to 12 months
Original Secondary Outcome Measures  ICMJE
 (submitted: February 1, 2006)
Change in total kidney volume as measured by 3D-CT from baseline to 12 months and adverse events.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pilot Study of Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Official Title  ICMJE Pilot Study of Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease
Brief Summary

This study is a prospective, randomized, open-label, pilot clinical trial designed to compare the effects of an agent that has antiproliferative (1,2), antiangiogenesis (3),and tumor-progression blocking capabilities (4), namely, rapamycin (Rapamune®), in the treatment of autosomal-dominant polycystic kidney disease (ADPKD).

Up to this time, only generic renal disease treatments for ADPKD have been in use, such as the treatment of hypertension, urinary tract infections, renal stones, renal call carcinomas, and replacement therapy with dialysis and/or renal transplantation. The fundamental aberrations in ADPKD are proliferation of cyst-forming tubuloepithelial cells, secretion of cytokine-rich fluid into those cysts, and progressive cyst expansion and release of inflammatory mediators that injure surrounding normal renal tissue. Consequently, therapy directed specifically at blocking the proliferation of tubuloepithelial cells and their tendency to malignant transformation, as well as impeding their blood supply, should have obvious merit.

General Procedures:

In Group I participants will have an iothalamate glomerular filtration rate (GFR) equal to or greater than 60 ml/min/1.73 m2, and in Group II participants will have a GFR less than 25-59 ml/min/1.73 m2. Both males and females with ADPKD who volunteer and qualify, will be randomly and prospectively assigned to treatment with rapamycin at either a high or low trough blood level or to standard care (each 1/3 of enrolled patients) for one year. The two treatment groups will receive rapamycin doses aimed at maintaining the 20- to 24-hour trough blood levels at either 2 to 5 ng/mL (low-dose), or greater than 5 to 8 ng/mL (high-dose). These trough levels are in the lower range of levels used when treating renal transplant recipients in whom trough levels are typically maintained between 5 and 15 ng/mL.

Detailed Description

This study is a prospective, randomized,open label, pilot clinical trial designed to compare the effects of an agent that has antiproliferative (1,2), antiangiogenesis (3),and tumor-progression blocking capabilities (4), namely, rapamycin (Rapamune®), in the treatment of autosomal-dominant polycystic kidney disease (ADPKD).

Up to this time, only generic renal disease treatments for ADPKD have been in use, such as the treatment of hypertension, urinary tract infections, renal stones, renal call carcinomas, and replacement therapy with dialysis and/or renal transplantation. The fundamental aberrations in ADPKD are proliferation of cyst-forming tubuloepithelial cells, secretion of cytokine-rich fluid into those cysts, and progressive cyst expansion and release of inflammatory mediators that injure surrounding normal renal tissue. Consequently, therapy directed specifically at blocking the proliferation of tubuloepithelial cells and their tendency to malignant transformation, as well as impeding their blood supply, should have obvious merit.

General Procedures:

In Group I participants will have an iothalamate glomerular filtration rate (GFR) equal to or greater than 60 ml/min/1.73 m2, and in Group II participants will have a GFR less than 25-59 ml/min/1.73 m2. Both males and females with ADPKD who volunteer and qualify, will be randomly and prospectively assigned to treatment with rapamycin at either a high or low trough blood level or to standard care (each 1/3 of enrolled patients) for one year. The two treatment groups will receive rapamycin doses aimed at maintaining the 20- to 24-hour trough blood levels at either 2 to 5 ng/mL (low-dose), or greater than 5 to 8 ng/mL (high-dose). These trough levels are in the lower range of levels used when treating renal transplant recipients in whom trough levels are typically maintained between 5 and 15 ng/mL.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Polycystic Kidney Diseases
Intervention  ICMJE Drug: Rapamune
Group 1- doses of Rapamune aimed at maintaining trough levels 5-8ng/ml Group 2 - doses of Rapamune aimed at maintaining trough levels 2-5ng/ml Group 3- Standard Care
Other Name: Rapamycin
Study Arms  ICMJE
  • Experimental: 1
    Arm 1 Rapamune dose 2-6mg aimed at maintaining trough levels 5-8 ng/ml
    Intervention: Drug: Rapamune
  • Experimental: 2
    Arm 2 Rapamune dose 2-6 mg aimed at maintaining trough levels of 2-5ng/ml
    Intervention: Drug: Rapamune
  • No Intervention: 3
    Standard Care
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 14, 2010)
30
Original Enrollment  ICMJE
 (submitted: February 1, 2006)
45
Actual Study Completion Date  ICMJE December 2014
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • ADPKD
  • > 18 y.o. GFR greater than or equal to 25. Willingness to be randomized to any treatment group Willingness to follow protocol requirements-frequent testing and follow-up required at Cleveland Clinic(Cleveland, OH) signed informed consent Willingness to use birth control(male and female)

Exclusion Criteria:

  • Pregnancy
  • post partum
  • lactating
  • system illness with renal involvement
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00286156
Other Study ID Numbers  ICMJE 7736
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party The Cleveland Clinic
Study Sponsor  ICMJE The Cleveland Clinic
Collaborators  ICMJE Wyeth is now a wholly owned subsidiary of Pfizer
Investigators  ICMJE
Principal Investigator: William E. Braun, MD The Cleveland Clinic
PRS Account The Cleveland Clinic
Verification Date March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP