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Pilot Study of Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD)

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ClinicalTrials.gov Identifier: NCT00286156
Recruitment Status : Completed
First Posted : February 3, 2006
Results First Posted : April 6, 2015
Last Update Posted : April 6, 2015
Sponsor:
Collaborator:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
The Cleveland Clinic

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Factorial Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Polycystic Kidney Diseases
Intervention Drug: Rapamune
Enrollment 30

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Standard Rapamycin Dose (STD) Low Dose Rapamycin (LD) Standard Care
Hide Arm/Group Description

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

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: fluid intake primarily water of 2500-3000ml/24hrs, low sodium diet of 2300mg/24 hrs, caffeine avoidance, control of hypertension
Period Title: Overall Study
Started 10 10 10
Completed 8 9 9
Not Completed 2 1 1
Reason Not Completed
Missed 12 month visit             0             0             1
AE: pulmonary embolus             0             1             0
AE: nephrotic-range proteinuruia             1             0             0
AE: pneumonia             1             0             0
Arm/Group Title Standard Rapamycin Dose (STD) Low Dose Rapamycin (LD) Standard Care Total
Hide Arm/Group Description

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

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: fluid intake primarily water of 2500-3000ml/24hrs, low sodium diet of 2300mg/24 hrs, caffeine avoidance, control of hypertension Total of all reporting groups
Overall Number of Baseline Participants 10 10 10 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 10 participants 10 participants 30 participants
53.2  (15.0) 44.9  (8.6) 49.4  (11.0) 49.3  (12.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 30 participants
Female
5
  50.0%
5
  50.0%
3
  30.0%
13
  43.3%
Male
5
  50.0%
5
  50.0%
7
  70.0%
17
  56.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 30 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
1
  10.0%
1
   3.3%
White
10
 100.0%
10
 100.0%
9
  90.0%
29
  96.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 10 participants 10 participants 10 participants 30 participants
10 10 10 30
Baseline characteristics and risk factors   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 30 participants
Hypertension 3 3 5 11
Family history of ESRD 4 8 7 19
Initial iGFR 25-59 ml/min per 1.73 m^2 3 4 2 9
Initial TKV>1500ml 6 7 6 19
Initial height-adjusted TKV>=600ml/m 6 8 6 20
[1]
Measure Description: ADPKD, autosomal dominant polycystic kidney disease; iGFR, 125I-iothalamate GFR; TKV, total kidney volume; Hypertension is a BP >= 140/90 mmHg before 35 years old; family history of ESRD occurs from ADPKD before 56 years old
1.Primary Outcome
Title Change in GFR From Baseline to 12 Months
Hide Description GFR (glomerular filtration rate) was measured by iothalamate. GFR is a key indicator of renal function.
Time Frame From baseline to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Standard Rapamycin Dose (STD) Low Dose Rapamycin (LD) Standard Care
Hide Arm/Group Description:

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

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: fluid intake primarily water of 2500-3000ml/24hrs, low sodium diet of 2300mg/24 hrs, caffeine avoidance, control of hypertension
Overall Number of Participants Analyzed 8 9 9
Mean (Standard Deviation)
Unit of Measure: ml/min/1.73m^2
Baseline iGFR 72.8  (25.7) 70.3  (27.0) 73.1  (20.3)
12 month iGFR 74.4  (34.4) 78.0  (35.0) 61.9  (15.6)
Change in iGFR 1.6  (12.1) 7.7  (12.5) -11.2  (9.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Standard Rapamycin Dose (STD), Low Dose Rapamycin (LD), Standard Care
Comments Null hypothesis: no difference between groups in iGFR
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments Pairwise comparisons adjusted for multiple testing (Tukey)
Method ANOVA
Comments [Not Specified]
2.Secondary Outcome
Title Change in Total Kidney Volume as Measured by 3D-CT From Baseline to 12 Months
Hide Description Total kidney volume measured by CT from baseline to 12 months
Time Frame From baseline to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Standard Rapamycin Dose (STD) Low Dose Rapamycin (LD) Standard Care
Hide Arm/Group Description:

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

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: fluid intake primarily water of 2500-3000ml/24hrs, low sodium diet of 2300mg/24 hrs, caffeine avoidance, control of hypertension
Overall Number of Participants Analyzed 8 9 9
Mean (Standard Deviation)
Unit of Measure: ml
Baseline TKV 1454.1  (801.5) 1919.1  (903.6) 1907.1  (1126.8)
12 month TKV 1537  (864.3) 2115.8  (1035.0) 2059.8  (1236.0)
Change in TKV 82.9  (111.3) 197.7  (201.2) 152.7  (129.4)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Standard Rapamycin Dose (STD) Low Dose Rapamycin (LD) Standard Care
Hide Arm/Group Description

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

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: fluid intake primarily water of 2500-3000ml/24hrs, low sodium diet of 2300mg/24 hrs, caffeine avoidance, control of hypertension
All-Cause Mortality
Standard Rapamycin Dose (STD) Low Dose Rapamycin (LD) Standard Care
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Standard Rapamycin Dose (STD) Low Dose Rapamycin (LD) Standard Care
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/10 (20.00%)      1/10 (10.00%)      1/10 (10.00%)    
Eye disorders       
Decrease visual acuity [1]  1/10 (10.00%)  0/10 (0.00%)  0/10 (0.00%) 
Metabolism and nutrition disorders       
Hypoglycemia [2]  0/10 (0.00%)  0/10 (0.00%)  1/10 (10.00%) 
Renal and urinary disorders       
nephrotic range proteinuria [3]  1/10 (10.00%)  0/10 (0.00%)  0/10 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
pulmonary embolus [4]  0/10 (0.00%)  1/10 (10.00%)  0/10 (0.00%) 
[1]
Patient developed transient decrease in visual acuity. Neuro-ophthalmologist did not find any association with drug. Vision improved without specific treatment.
[2]
Hypoglycemia associated with excessive beer consumption.
[3]
Open renal biopsy showed FSGS. Primary glomerulopathies have been reported to be superimposed on underlying ADPKD.
[4]
Patient had massive polycystic kidneys (about 7500ml) and there was compression of the right iliac vein/IVC with clot formation. This has been reported in the literature, so it is not necessarily related to drug.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Standard Rapamycin Dose (STD) Low Dose Rapamycin (LD) Standard Care
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/10 (100.00%)      6/10 (60.00%)      8/10 (80.00%)    
Blood and lymphatic system disorders       
Edema  1/10 (10.00%)  1 0/10 (0.00%)  0 2/10 (20.00%)  2
Gastrointestinal disorders       
Gastrointestinal symptoms  3/10 (30.00%)  3 1/10 (10.00%)  1 4/10 (40.00%)  5
General disorders       
Miscellaneous/other [1]  4/10 (40.00%)  7 2/10 (20.00%)  2 5/10 (50.00%)  7
Immune system disorders       
Oral ulcerations  6/10 (60.00%)  6 2/10 (20.00%)  2 0/10 (0.00%)  0
Infections and infestations       
Nonserious infections  6/10 (60.00%)  6 2/10 (20.00%)  2 5/10 (50.00%)  5
Skin and subcutaneous tissue disorders       
Dermatitis  0/10 (0.00%)  0 2/10 (20.00%)  2 0/10 (0.00%)  0
[1]
The problems in this group were minor, extremely varied and transient.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr William Braun Consultant Staff Nephrology, Cleveland Clinic
Organization: Cleveland Clinic
Phone: 216/444/6995
Responsible Party: The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT00286156     History of Changes
Other Study ID Numbers: 7736
First Submitted: February 1, 2006
First Posted: February 3, 2006
Results First Submitted: March 31, 2015
Results First Posted: April 6, 2015
Last Update Posted: April 6, 2015