Pilot Study of Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Status:
Completed
Trial end date:
2014-12-01
Target enrollment:
Participant gender:
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.