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Pilot Study of Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Primary Purpose

Polycystic Kidney Diseases

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Rapamune
Sponsored by
The Cleveland Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polycystic Kidney Diseases focused on measuring ADPKD

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The Cleveland Clinic- main campus

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

No Intervention

Arm Label

1

2

3

Arm Description

Arm 1 Rapamune dose 2-6mg aimed at maintaining trough levels 5-8 ng/ml

Arm 2 Rapamune dose 2-6 mg aimed at maintaining trough levels of 2-5ng/ml

Standard Care

Outcomes

Primary Outcome Measures

Change in GFR From Baseline to 12 Months
GFR (glomerular filtration rate) was measured by iothalamate. GFR is a key indicator of renal function.

Secondary Outcome Measures

Change in Total Kidney Volume as Measured by 3D-CT From Baseline to 12 Months
Total kidney volume measured by CT from baseline to 12 months

Full Information

First Posted
February 1, 2006
Last Updated
March 31, 2015
Sponsor
The Cleveland Clinic
Collaborators
Wyeth is now a wholly owned subsidiary of Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT00286156
Brief Title
Pilot Study of Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Official Title
Pilot Study of Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease
Study Type
Interventional

2. Study Status

Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
October 2006 (undefined)
Primary Completion Date
March 2012 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Cleveland Clinic
Collaborators
Wyeth is now a wholly owned subsidiary of Pfizer

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Kidney Diseases
Keywords
ADPKD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Arm 1 Rapamune dose 2-6mg aimed at maintaining trough levels 5-8 ng/ml
Arm Title
2
Arm Type
Experimental
Arm Description
Arm 2 Rapamune dose 2-6 mg aimed at maintaining trough levels of 2-5ng/ml
Arm Title
3
Arm Type
No Intervention
Arm Description
Standard Care
Intervention Type
Drug
Intervention Name(s)
Rapamune
Other Intervention Name(s)
Rapamycin
Intervention Description
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
Primary Outcome Measure Information:
Title
Change in GFR From Baseline to 12 Months
Description
GFR (glomerular filtration rate) was measured by iothalamate. GFR is a key indicator of renal function.
Time Frame
From baseline to 12 months
Secondary Outcome Measure Information:
Title
Change in Total Kidney Volume as Measured by 3D-CT From Baseline to 12 Months
Description
Total kidney volume measured by CT from baseline to 12 months
Time Frame
From baseline to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William E. Braun, MD
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Cleveland Clinic- main campus
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Pilot Study of Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD)

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