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

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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

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 Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Change in GFR From Baseline to 12 Months

Secondary Outcome

 Change in Total Kidney Volume as Measured by 3D-CT From Baseline to 12 Months

Condition

Polycystic Kidney Diseases

Intervention

Rapamune

Study Arms / Comparison Groups

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

30

Start Date

October 2006

Completion Date

December 2014

Primary Completion Date

March 2012

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
      

Gender

All

Ages

18 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

William E. Braun, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00286156

Organization ID

7736


Responsible Party

Sponsor

Study Sponsor

The Cleveland Clinic

Collaborators

 Wyeth is now a wholly owned subsidiary of Pfizer

Study Sponsor

William E. Braun, MD, Principal Investigator, The Cleveland Clinic


Verification Date

March 2014