Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD): The Role of Biomarkers in Predicting a Response to Therapy

Yale University

Status and phase: Terminated; Phase 3; Phase 2

Conditions: Autosomal Dominant Polycystic Kidney Disease

Treatments: Other: Standard of Care-Placebo; Drug: Rapamycin

Study type: Interventional

Funder types: Other

Identifiers

NCT00920309

HIC#0903004934

Details and patient eligibility

About

Currently the only approved use for rapamycin (sirolimus) is for immunosuppression after renal transplantation.

This trial is designed to determine whether rapamycin is safe and effective treatment for patients with polycystic kidney disease (ADPKD). Patients will be followed by volumetric magnetic resonance imaging (MRI) to observe for change in kidney (and cyst) size. Blood and urine samples will also be collected to evaluate for change in biomarkers with treatment.

Full description

This is a 2 year, open label trial to evaluate the role of rapamycin as treatment for ADPKD. Patients will be randomized 2:1 to the rapamycin arm or to standard therapy. The dose of rapamycin will be adjusted so that patients obtain 24 trough levels of 4-6ng/ml. There will be a volumetric MRI measurement at the start and end of the treatment period. Patients will be monitored every 4 months throughout the study.

Enrollment: 21 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• adult ADPKD patients aged 18-70
• combined kidney volume >1200 ml
• estimated creatinine clearance >60 ml/min
• absence of implanted ferromagnetic objects

Exclusion criteria

• Age >70
• uncontrolled hyperlipidemia
• Proteinuria >500 mg/day
• unstable cerebral aneurysm
• active coronary artery disease
• diagnosis of another systemic condition affecting kidney function (ie: diabetes, hepatitis B or C, HIV)
• diagnosis of cancer other than skin cancer
• pregnancy or lactation
• presence of implanted ferromagnetic objects

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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21 participants in 2 patient groups, including a placebo group

Rapamycin

Experimental group

Description:

Drug: Rapamycin Other Names: sirolimus The starting dose of rapamycin will be 1 mg daily. The dose will be increased as needed to achieve a 24 hour trough level of 4-6 ng/ml.

Treatment:

Drug: Rapamycin

Standard of Care-Placebo

Placebo Comparator group

Description:

Standard of Care

Treatment:

Other: Standard of Care-Placebo