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Use of Low Dose Pioglitazone to Treat Autosomal Dominant Polycystic Kidney Disease (PIOPKD)

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ClinicalTrials.gov Identifier: NCT02697617
Recruitment Status : Completed
First Posted : March 3, 2016
Results First Posted : January 15, 2021
Last Update Posted : January 15, 2021
Sponsor:
Information provided by (Responsible Party):
Sharon Moe, Indiana University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Polycystic Kidney Disease
Interventions Drug: Pioglitazone
Drug: Placebo
Enrollment 18
Recruitment Details Age 18-55 years old, with known autosomal dominant polycystic kidney disease (ADPKD), estimated glomerular filtration rate (eGFR) > 50 ml/min/m2 on recent labs, and no history of diabetes were identified using international disease codes (ICD-9) code for cystic kidney disease by search of electronic medical records or through advertisements and letters sent to Nephrologists.
Pre-assignment Details Patients who fulfilled the initial screening underwent further screening with a baseline magnetic resonance imaging (MRI) and randomized to pioglitazone or placebo providing the total kidney volume (TKV) was ≥675 ml (18-25 years old), ≥ 900 ml (26-35 years old), and ≥ 1350 ml (36-55 years old).
Arm/Group Title PIO Then PLACEBO Placebo Then PIO
Hide Arm/Group Description Sequence Pioglitazone then Placebo sequence placebo then pioglitazone
Period Title: Overall Study
Started 9 9
Completed 8 [1] 7
Not Completed 1 2
Reason Not Completed
Withdrawal by Subject             0             2
Pregnancy             1             0
[1]
15 completed both arms
Arm/Group Title All Study Participants
Hide Arm/Group Description at randomization to sequence 1 (pioglitazone 15 mg) or placebo for cross over study
Overall Number of Baseline Participants 18
Hide Baseline Analysis Population Description
18 patients randomized to either pioglitazone for 12 months and then placebo for 12 months and then cross over to the other arm. So baseline data represents both arms
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants
<=18 years
0
   0.0%
Between 18 and 65 years
18
 100.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants
34.2  (7.54)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants
Female
11
  61.1%
Male
7
  38.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
13
  72.2%
Unknown or Not Reported
5
  27.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
13
  72.2%
More than one race
0
   0.0%
Unknown or Not Reported
5
  27.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 18 participants
18
estimated glomerular filtration rate (eGFR) by CKD-epi  
Mean (Standard Deviation)
Unit of measure:  Ml/min/m2
Number Analyzed 18 participants
86  (27)
right kidney volume  
Mean (Standard Deviation)
Unit of measure:  Ml
Number Analyzed 18 participants
965  (636)
left kidney volume  
Mean (Standard Deviation)
Unit of measure:  Ml
Number Analyzed 18 participants
1078  (652)
1.Primary Outcome
Title Safety: Total Body Water
Hide Description Bioimpedance analysis (BIA)(Ohms); Increase in BIA in Ohms indicates a decrease in total body water
Time Frame average of 4 measures in each 12 month arm
Hide Outcome Measure Data
Hide Analysis Population Description
All patients randomized
Arm/Group Title Pioglitazone Placebo
Hide Arm/Group Description:
Total body water
Total Body Water
Overall Number of Participants Analyzed 18 18
Mean (95% Confidence Interval)
Unit of Measure: Ohms
45.78
(39.19 to 52.36)
44.17
(37.96 to 50.39)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.024
Comments First analyzed using a Linear Mixed Model to assess if there were carryover effects and then subsequently analyzed using paired t-tests to compare the mean differences between treatments.
Method Paired t-test
Comments [Not Specified]
2.Primary Outcome
Title Efficacy: Percent Change in Total Kidney Volume
Hide Description Change in total kidney volume by Magnetic Resonance Imaging (MRI) from beginning to end of the 12 months
Time Frame Baseline, end of year 1, and end of year 2
Hide Outcome Measure Data
Hide Analysis Population Description
Those who completed both arms
Arm/Group Title Pioglitazone 15 mg Daily Placebo po Daily
Hide Arm/Group Description:
Patients who completed both arms, data from the 12 months of pioglitazone treatment
of patients who finished both arms, the results from the placebo arm
Overall Number of Participants Analyzed 15 15
Mean (95% Confidence Interval)
Unit of Measure: percentage of change
4.35
(0.84 to 7.86)
7.85
(3.6 to 12.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg Daily, Placebo po Daily
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.14
Comments First analyzed using a Linear Mixed Model to assess if there were carryover effects and then subsequently analyzed using paired t-tests to compare the mean differences between treatments.
Method Paired t-test
Comments [Not Specified]
3.Secondary Outcome
Title Safety: Hypoglycemia
Hide Description number of patients with blood sugar < 70 mg/dl
Time Frame measured quarterly for 12 months in pioglitazone and same in placebo
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Pioglitazone 15 mg Placebo
Hide Arm/Group Description:
All patients taking pioglitazone
all patients taking placebo
Overall Number of Participants Analyzed 18 18
Measure Type: Count of Participants
Unit of Measure: Participants
1
   5.6%
1
   5.6%
4.Secondary Outcome
Title Safety: Elevated Liver Function Tests
Hide Description Number of patients with elevated liver test (ALT or AST) > 2 times upper limit of normal
Time Frame measured quarterly over 12 months for each arm
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who were randomized, regardless of whether they completed both arms
Arm/Group Title Pioglitazone 15 mg Placebo
Hide Arm/Group Description:
All patients taking pioglitazone
all patients taking placebo
Overall Number of Participants Analyzed 18 18
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
1
   5.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Other Statistical Analysis comparison by paired t-test
5.Secondary Outcome
Title Efficacy: Glomerular Filtration Rate
Hide Description average estimated glomerular filtration rate by chronic kidney disease (CKD) epidemiologic (epi) formula measured quarterly
Time Frame average of 4 values over 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All patients that completed both arms.
Arm/Group Title Pioglitazone 15 mg Placebo
Hide Arm/Group Description:
All patients taking pioglitazone
all patients taking placebo
Overall Number of Participants Analyzed 15 15
Mean (95% Confidence Interval)
Unit of Measure: ml/min/m2
75.5
(62 to 89)
78.1
(64 to 92)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments First analyzed using a Linear Mixed Model to assess if there were carryover effects and then subsequently analyzed using paired t-tests to compare the mean differences between treatments.
Method Paired t-test
Comments [Not Specified]
6.Secondary Outcome
Title Efficacy Blood Pressure
Hide Description mean systolic and diastolic blood pressure
Time Frame average of 4 measures over 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All patients that completed both arms
Arm/Group Title Pioglitazone 15 mg Placebo
Hide Arm/Group Description:
All patients taking pioglitazone
all patients taking placebo
Overall Number of Participants Analyzed 15 15
Mean (95% Confidence Interval)
Unit of Measure: mmHg
systolic blood pressure
127
(124 to 130)
129
(124 to 134)
diastolic blood pressure
83
(81 to 86)
82
(82 to 89)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone 15 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4
Comments First analyzed using a Linear Mixed Model to assess if there were carryover effects and then subsequently analyzed using paired t-tests to compare the mean differences between treatments.
Method paired t test
Comments [Not Specified]
7.Secondary Outcome
Title Bone Marrow Fat
Hide Description We will assess change in bone marrow fat by MR spectroscopy as an ancillary study to be done at the same time as MRI; will not be done due to person leaving institution.
Time Frame Baseline, end of year 1, and end of year 2
Hide Outcome Measure Data
Hide Analysis Population Description
The MRIs were done, but could not be analyzed as requires special expertise and software.
Arm/Group Title Pioglitazone 15 mg Daily Placebo po Daily
Hide Arm/Group Description:
Patients who completed both arms, data from the 12 months of pioglitazone treatment
of patients who finished both arms, the results from the placebo arm
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame 2 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Pioglitazone Placebo
Hide Arm/Group Description 15 mg po daily Over encapsulated (identical appearing) placebo
All-Cause Mortality
Pioglitazone Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/18 (0.00%)      0/18 (0.00%)    
Hide Serious Adverse Events
Pioglitazone Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/18 (0.00%)      3/18 (16.67%)    
Gastrointestinal disorders     
surgery * [1]  0/18 (0.00%)  0 1/18 (5.56%)  1
Hepatobiliary disorders     
hospitalization * [2]  0/18 (0.00%)  0 1/18 (5.56%)  1
Infections and infestations     
pyelonephritis *  0/18 (0.00%)  0 1/18 (5.56%)  1
*
Indicates events were collected by non-systematic assessment
[1]
elective surgery/gastric banding
[2]
pancreatitis
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pioglitazone Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/18 (72.22%)      15/18 (83.33%)    
Gastrointestinal disorders     
gastrointestinal symptom *  6/18 (33.33%)  9 5/18 (27.78%)  10
General disorders     
urinary tract infection or pain * [1]  7/18 (38.89%)  12 9/18 (50.00%)  18
Infections and infestations     
infection *  13/18 (72.22%)  38 15/18 (83.33%)  30
Musculoskeletal and connective tissue disorders     
musculoskeletal pain *  7/18 (38.89%)  17 9/18 (50.00%)  23
Nervous system disorders     
headache *  8/18 (44.44%)  12 9/18 (50.00%)  11
dizziness *  4/18 (22.22%)  6 3/18 (16.67%)  6
*
Indicates events were collected by non-systematic assessment
[1]
or cyst rupture
The major limitation is the small sample size.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Sharon Moe
Organization: Indiana University School of Medicine
Phone: 317 278 2868
EMail: smoe@iu.edu
Layout table for additonal information
Responsible Party: Sharon Moe, Indiana University
ClinicalTrials.gov Identifier: NCT02697617    
Other Study ID Numbers: IndianaU 1308084213
FD-R-004826-01-A2 ( Other Identifier: FDA Orphan Products Development Ad Hoc Panel Review )
First Submitted: October 30, 2015
First Posted: March 3, 2016
Results First Submitted: October 19, 2020
Results First Posted: January 15, 2021
Last Update Posted: January 15, 2021