Autosomal Dominant Polycystic Kidney Disease
Conditions
Keywords
Autosomal Dominant Polycystic Kidney Disease, rapamycin, ADPKD
Brief summary
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.
Detailed 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.
Interventions
DRUGRapamycin
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.
OTHERStandard of Care-Placebo
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Total Kidney Volume (mL) | 2 years |
Secondary
| Measure | Time frame |
|---|---|
| Glomerular Filtration Rate (Kidney Function) | 2 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rapamycin 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. | 14 |
| Standard of Care-Placebo | 7 |
| Total | 21 |
Baseline characteristics
| Characteristic | Rapamycin | Standard of Care-Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 7 Participants | 20 Participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 9 Participants | 5 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 14 | 0 / 7 |
| serious Total, serious adverse events | 3 / 14 | 0 / 7 |
Outcome results
Primary
Total Kidney Volume (mL)
Time frame: 2 years
Population: Outcome Measures were not analyzed due to study termination
Secondary
Glomerular Filtration Rate (Kidney Function)
Time frame: 2 years
Population: Outcome measures were not analyzed due to study termination