Trial Outcomes & Findings for Pilot Study of Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD) (NCT NCT00286156)
NCT ID: NCT00286156
Last Updated: 2015-04-06
Results Overview
GFR (glomerular filtration rate) was measured by iothalamate. GFR is a key indicator of renal function.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
30 participants
Primary outcome timeframe
From baseline to 12 months
Results posted on
2015-04-06
Participant Flow
Participant milestones
| Measure |
Standard Rapamycin Dose (STD)
Arm 1 Rapamune dose 2-6mg aimed at maintaining trough levels 5-8 ng/ml
Rapamycin: Group 1- doses of Rapamune aimed at maintaining trough levels 5-8ng/ml
|
Low Dose Rapamycin (LD)
Arm 2 Rapamune dose 2-6 mg aimed at maintaining trough levels of 2-5ng/ml
Rapamycin: Group 2 - doses of Rapamune aimed at maintaining trough levels 2-5ng/ml
|
Standard Care
Standard Care: fluid intake primarily water of 2500-3000ml/24hrs, low sodium diet of 2300mg/24 hrs, caffeine avoidance, control of hypertension
|
|---|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
10
|
|
Overall Study
COMPLETED
|
8
|
9
|
9
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
1
|
Reasons for withdrawal
| Measure |
Standard Rapamycin Dose (STD)
Arm 1 Rapamune dose 2-6mg aimed at maintaining trough levels 5-8 ng/ml
Rapamycin: Group 1- doses of Rapamune aimed at maintaining trough levels 5-8ng/ml
|
Low Dose Rapamycin (LD)
Arm 2 Rapamune dose 2-6 mg aimed at maintaining trough levels of 2-5ng/ml
Rapamycin: Group 2 - doses of Rapamune aimed at maintaining trough levels 2-5ng/ml
|
Standard Care
Standard Care: fluid intake primarily water of 2500-3000ml/24hrs, low sodium diet of 2300mg/24 hrs, caffeine avoidance, control of hypertension
|
|---|---|---|---|
|
Overall Study
Missed 12 month visit
|
0
|
0
|
1
|
|
Overall Study
AE: pulmonary embolus
|
0
|
1
|
0
|
|
Overall Study
AE: nephrotic-range proteinuruia
|
1
|
0
|
0
|
|
Overall Study
AE: pneumonia
|
1
|
0
|
0
|
Baseline Characteristics
Pilot Study of Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Baseline characteristics by cohort
| Measure |
Standard Rapamycin Dose (STD)
n=10 Participants
Arm 1 Rapamune dose 2-6mg aimed at maintaining trough levels 5-8 ng/ml
Rapamycin: Group 1- doses of Rapamune aimed at maintaining trough levels 5-8ng/ml
|
Low Dose Rapamycin (LD)
n=10 Participants
Arm 2 Rapamune dose 2-6 mg aimed at maintaining trough levels of 2-5ng/ml
Rapamycin: Group 2 - doses of Rapamune aimed at maintaining trough levels 2-5ng/ml
|
Standard Care
n=10 Participants
Standard Care: fluid intake primarily water of 2500-3000ml/24hrs, low sodium diet of 2300mg/24 hrs, caffeine avoidance, control of hypertension
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
53.2 years
STANDARD_DEVIATION 15.0 • n=5 Participants
|
44.9 years
STANDARD_DEVIATION 8.6 • n=7 Participants
|
49.4 years
STANDARD_DEVIATION 11.0 • n=5 Participants
|
49.3 years
STANDARD_DEVIATION 12.0 • n=4 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
29 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
10 participants
n=7 Participants
|
10 participants
n=5 Participants
|
30 participants
n=4 Participants
|
|
Baseline characteristics and risk factors
Hypertension
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
5 participants
n=5 Participants
|
11 participants
n=4 Participants
|
|
Baseline characteristics and risk factors
Family history of ESRD
|
4 participants
n=5 Participants
|
8 participants
n=7 Participants
|
7 participants
n=5 Participants
|
19 participants
n=4 Participants
|
|
Baseline characteristics and risk factors
Initial iGFR 25-59 ml/min per 1.73 m^2
|
3 participants
n=5 Participants
|
4 participants
n=7 Participants
|
2 participants
n=5 Participants
|
9 participants
n=4 Participants
|
|
Baseline characteristics and risk factors
Initial TKV>1500ml
|
6 participants
n=5 Participants
|
7 participants
n=7 Participants
|
6 participants
n=5 Participants
|
19 participants
n=4 Participants
|
|
Baseline characteristics and risk factors
Initial height-adjusted TKV>=600ml/m
|
6 participants
n=5 Participants
|
8 participants
n=7 Participants
|
6 participants
n=5 Participants
|
20 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: From baseline to 12 monthsGFR (glomerular filtration rate) was measured by iothalamate. GFR is a key indicator of renal function.
Outcome measures
| Measure |
Standard Rapamycin Dose (STD)
n=8 Participants
Arm 1 Rapamune dose 2-6mg aimed at maintaining trough levels 5-8 ng/ml
Rapamycin: Group 1- doses of Rapamune aimed at maintaining trough levels 5-8ng/ml
|
Low Dose Rapamycin (LD)
n=9 Participants
Arm 2 Rapamune dose 2-6 mg aimed at maintaining trough levels of 2-5ng/ml
Rapamycin: Group 2 - doses of Rapamune aimed at maintaining trough levels 2-5ng/ml
|
Standard Care
n=9 Participants
Standard Care: fluid intake primarily water of 2500-3000ml/24hrs, low sodium diet of 2300mg/24 hrs, caffeine avoidance, control of hypertension
|
|---|---|---|---|
|
Change in GFR From Baseline to 12 Months
Baseline iGFR
|
72.8 ml/min/1.73m^2
Standard Deviation 25.7
|
70.3 ml/min/1.73m^2
Standard Deviation 27.0
|
73.1 ml/min/1.73m^2
Standard Deviation 20.3
|
|
Change in GFR From Baseline to 12 Months
12 month iGFR
|
74.4 ml/min/1.73m^2
Standard Deviation 34.4
|
78.0 ml/min/1.73m^2
Standard Deviation 35.0
|
61.9 ml/min/1.73m^2
Standard Deviation 15.6
|
|
Change in GFR From Baseline to 12 Months
Change in iGFR
|
1.6 ml/min/1.73m^2
Standard Deviation 12.1
|
7.7 ml/min/1.73m^2
Standard Deviation 12.5
|
-11.2 ml/min/1.73m^2
Standard Deviation 9.1
|
SECONDARY outcome
Timeframe: From baseline to 12 monthsTotal kidney volume measured by CT from baseline to 12 months
Outcome measures
| Measure |
Standard Rapamycin Dose (STD)
n=8 Participants
Arm 1 Rapamune dose 2-6mg aimed at maintaining trough levels 5-8 ng/ml
Rapamycin: Group 1- doses of Rapamune aimed at maintaining trough levels 5-8ng/ml
|
Low Dose Rapamycin (LD)
n=9 Participants
Arm 2 Rapamune dose 2-6 mg aimed at maintaining trough levels of 2-5ng/ml
Rapamycin: Group 2 - doses of Rapamune aimed at maintaining trough levels 2-5ng/ml
|
Standard Care
n=9 Participants
Standard Care: fluid intake primarily water of 2500-3000ml/24hrs, low sodium diet of 2300mg/24 hrs, caffeine avoidance, control of hypertension
|
|---|---|---|---|
|
Change in Total Kidney Volume as Measured by 3D-CT From Baseline to 12 Months
Baseline TKV
|
1454.1 ml
Standard Deviation 801.5
|
1919.1 ml
Standard Deviation 903.6
|
1907.1 ml
Standard Deviation 1126.8
|
|
Change in Total Kidney Volume as Measured by 3D-CT From Baseline to 12 Months
12 month TKV
|
1537 ml
Standard Deviation 864.3
|
2115.8 ml
Standard Deviation 1035.0
|
2059.8 ml
Standard Deviation 1236.0
|
|
Change in Total Kidney Volume as Measured by 3D-CT From Baseline to 12 Months
Change in TKV
|
82.9 ml
Standard Deviation 111.3
|
197.7 ml
Standard Deviation 201.2
|
152.7 ml
Standard Deviation 129.4
|
Adverse Events
Standard Rapamycin Dose (STD)
Serious events: 2 serious events
Other events: 10 other events
Deaths: 0 deaths
Low Dose Rapamycin (LD)
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Standard Care
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Standard Rapamycin Dose (STD)
n=10 participants at risk
Arm 1 Rapamune dose 2-6mg aimed at maintaining trough levels 5-8 ng/ml
Rapamycin: Group 1- doses of Rapamune aimed at maintaining trough levels 5-8ng/ml
|
Low Dose Rapamycin (LD)
n=10 participants at risk
Arm 2 Rapamune dose 2-6 mg aimed at maintaining trough levels of 2-5ng/ml
Rapamycin: Group 2 - doses of Rapamune aimed at maintaining trough levels 2-5ng/ml
|
Standard Care
n=10 participants at risk
Standard Care: fluid intake primarily water of 2500-3000ml/24hrs, low sodium diet of 2300mg/24 hrs, caffeine avoidance, control of hypertension
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
pulmonary embolus
|
0.00%
0/10
|
10.0%
1/10
|
0.00%
0/10
|
|
Renal and urinary disorders
nephrotic range proteinuria
|
10.0%
1/10
|
0.00%
0/10
|
0.00%
0/10
|
|
Eye disorders
Decrease visual acuity
|
10.0%
1/10
|
0.00%
0/10
|
0.00%
0/10
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
0.00%
0/10
|
0.00%
0/10
|
10.0%
1/10
|
Other adverse events
| Measure |
Standard Rapamycin Dose (STD)
n=10 participants at risk
Arm 1 Rapamune dose 2-6mg aimed at maintaining trough levels 5-8 ng/ml
Rapamycin: Group 1- doses of Rapamune aimed at maintaining trough levels 5-8ng/ml
|
Low Dose Rapamycin (LD)
n=10 participants at risk
Arm 2 Rapamune dose 2-6 mg aimed at maintaining trough levels of 2-5ng/ml
Rapamycin: Group 2 - doses of Rapamune aimed at maintaining trough levels 2-5ng/ml
|
Standard Care
n=10 participants at risk
Standard Care: fluid intake primarily water of 2500-3000ml/24hrs, low sodium diet of 2300mg/24 hrs, caffeine avoidance, control of hypertension
|
|---|---|---|---|
|
Immune system disorders
Oral ulcerations
|
60.0%
6/10 • Number of events 6
|
20.0%
2/10 • Number of events 2
|
0.00%
0/10
|
|
Infections and infestations
Nonserious infections
|
60.0%
6/10 • Number of events 6
|
20.0%
2/10 • Number of events 2
|
50.0%
5/10 • Number of events 5
|
|
Blood and lymphatic system disorders
Edema
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
20.0%
2/10 • Number of events 2
|
|
Gastrointestinal disorders
Gastrointestinal symptoms
|
30.0%
3/10 • Number of events 3
|
10.0%
1/10 • Number of events 1
|
40.0%
4/10 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/10
|
20.0%
2/10 • Number of events 2
|
0.00%
0/10
|
|
General disorders
Miscellaneous/other
|
40.0%
4/10 • Number of events 7
|
20.0%
2/10 • Number of events 2
|
50.0%
5/10 • Number of events 7
|
Additional Information
Dr William Braun Consultant Staff Nephrology, Cleveland Clinic
Cleveland Clinic
Phone: 216/444/6995
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place