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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
The Cleveland Clinic
ClinicalTrials.gov Identifier:
NCT00286156
First received: February 1, 2006
Last updated: February 17, 2014
Last verified: February 2014

February 1, 2006
February 17, 2014
October 2006
March 2012   (final data collection date for primary outcome measure)
Change in GFR from baseline to 12 months [ Time Frame: From study enrollment ] [ Designated as safety issue: No ]
Change in Iothalamate GFR from baseline to 12 months
Complete list of historical versions of study NCT00286156 on ClinicalTrials.gov Archive Site
Change in total kidney volume as measured by 3D-CT from baseline to 12 months and adverse events. [ Time Frame: from study enrollment ] [ Designated as safety issue: No ]
Change in total kidney volume as measured by 3D-CT from baseline to 12 months and adverse events.
Not Provided
Not Provided
 
Pilot Study of Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Pilot Study of Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Polycystic Kidney Diseases
Drug: Rapamycin
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: Rapamune
  • Experimental: 1
    Arm 1 Rapamune dose 2-6mg aimed at maintaining trough levels 5-8 ng/ml
    Intervention: Drug: Rapamycin
  • Experimental: 2
    Arm 2 Rapamune dose 2-6 mg aimed at maintaining trough levels of 2-5ng/ml
    Intervention: Drug: Rapamycin
  • No Intervention: 3
    Standard Care
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
30
November 2014
March 2012   (final data collection date for primary outcome measure)

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
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00286156
7736
Yes
The Cleveland Clinic
The Cleveland Clinic
Wyeth is now a wholly owned subsidiary of Pfizer
Principal Investigator: William E. Braun, MD The Cleveland Clinic
The Cleveland Clinic
February 2014

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