Pilot Study of Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Condition: Polycystic Kidney Diseases
MeSH terms: Kidney Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): Rapamune
Intervention type(s): Drug
Intervention description(s): 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 intervention name(s): Rapamycin
Intervention MeSH terms: Sirolimus
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: ADPKD