Trial Outcomes & Findings for Use of Low Dose Pioglitazone to Treat Autosomal Dominant Polycystic Kidney Disease (NCT NCT02697617)

NCT ID: NCT02697617

Last Updated: 2021-01-15

Results Overview

Bioimpedance analysis (BIA)(Ohms); Increase in BIA in Ohms indicates a decrease in total body water

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 18 participants
• Primary outcome timeframe: average of 4 measures in each 12 month arm
• Results posted on: 2021-01-15

Participant Flow

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.

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).

Participant milestones

Measure	PIO Then PLACEBO Sequence Pioglitazone then Placebo	Placebo Then PIO sequence placebo then pioglitazone
Overall Study STARTED	9	9
Overall Study COMPLETED	8	7
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Measure	PIO Then PLACEBO Sequence Pioglitazone then Placebo	Placebo Then PIO sequence placebo then pioglitazone
Overall Study Withdrawal by Subject	0	2
Overall Study Pregnancy	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	All Study Participants n=18 Participants at randomization to sequence 1 (pioglitazone 15 mg) or placebo for cross over study
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	18 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	34.2 years STANDARD_DEVIATION 7.54 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	13 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants
Region of Enrollment United States	18 participants n=5 Participants
estimated glomerular filtration rate (eGFR) by CKD-epi	86 ml/min/m2 STANDARD_DEVIATION 27 • n=5 Participants
right kidney volume	965 ml STANDARD_DEVIATION 636 • n=5 Participants
left kidney volume	1078 ml STANDARD_DEVIATION 652 • n=5 Participants

PRIMARY outcome

Timeframe: average of 4 measures in each 12 month arm

Population: All patients randomized

Bioimpedance analysis (BIA)(Ohms); Increase in BIA in Ohms indicates a decrease in total body water

Outcome measures

Measure	Pioglitazone n=18 Participants Total body water	Placebo n=18 Participants Total Body Water
Safety: Total Body Water	45.78 Ohms Interval 39.19 to 52.36	44.17 Ohms Interval 37.96 to 50.39

PRIMARY outcome

Timeframe: Baseline, end of year 1, and end of year 2

Population: Those who completed both arms

Change in total kidney volume by Magnetic Resonance Imaging (MRI) from beginning to end of the 12 months

Outcome measures

Measure	Pioglitazone n=15 Participants Total body water	Placebo n=15 Participants Total Body Water
Efficacy: Percent Change in Total Kidney Volume	4.35 percentage of change Interval 0.84 to 7.86	7.85 percentage of change Interval 3.6 to 12.11

SECONDARY outcome

Timeframe: measured quarterly for 12 months in pioglitazone and same in placebo

Population: All randomized participants

number of patients with blood sugar < 70 mg/dl

Outcome measures

Measure	Pioglitazone n=18 Participants Total body water	Placebo n=18 Participants Total Body Water
Safety: Hypoglycemia	1 Participants	1 Participants

SECONDARY outcome

Timeframe: measured quarterly over 12 months for each arm

Population: All patients who were randomized, regardless of whether they completed both arms

Number of patients with elevated liver test (ALT or AST) > 2 times upper limit of normal

Outcome measures

Measure	Pioglitazone n=18 Participants Total body water	Placebo n=18 Participants Total Body Water
Safety: Elevated Liver Function Tests	0 Participants	1 Participants

SECONDARY outcome

Timeframe: average of 4 values over 12 months

Population: All patients that completed both arms.

average estimated glomerular filtration rate by chronic kidney disease (CKD) epidemiologic (epi) formula measured quarterly

Outcome measures

Measure	Pioglitazone n=15 Participants Total body water	Placebo n=15 Participants Total Body Water
Efficacy: Glomerular Filtration Rate	75.5 ml/min/m2 Interval 62.0 to 89.0	78.1 ml/min/m2 Interval 64.0 to 92.0

SECONDARY outcome

Timeframe: average of 4 measures over 12 months

Population: All patients that completed both arms

mean systolic and diastolic blood pressure

Outcome measures

Measure	Pioglitazone n=15 Participants Total body water	Placebo n=15 Participants Total Body Water
Efficacy Blood Pressure systolic blood pressure	127 mmHg Interval 124.0 to 130.0	129 mmHg Interval 124.0 to 134.0
Efficacy Blood Pressure diastolic blood pressure	83 mmHg Interval 81.0 to 86.0	82 mmHg Interval 82.0 to 89.0

SECONDARY outcome

Timeframe: Baseline, end of year 1, and end of year 2

Population: The MRIs were done, but could not be analyzed as requires special expertise and software.

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.

Outcome measures

Outcome data not reported

Adverse Events

Pioglitazone

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pioglitazone n=18 participants at risk 15 mg po daily	Placebo n=18 participants at risk Over encapsulated (identical appearing) placebo
Hepatobiliary disorders hospitalization	0.00% 0/18 • 2 years	5.6% 1/18 • Number of events 1 • 2 years
Infections and infestations pyelonephritis	0.00% 0/18 • 2 years	5.6% 1/18 • Number of events 1 • 2 years
Gastrointestinal disorders surgery	0.00% 0/18 • 2 years	5.6% 1/18 • Number of events 1 • 2 years

Other adverse events

Measure	Pioglitazone n=18 participants at risk 15 mg po daily	Placebo n=18 participants at risk Over encapsulated (identical appearing) placebo
Nervous system disorders headache	44.4% 8/18 • Number of events 12 • 2 years	50.0% 9/18 • Number of events 11 • 2 years
Nervous system disorders dizziness	22.2% 4/18 • Number of events 6 • 2 years	16.7% 3/18 • Number of events 6 • 2 years
Infections and infestations infection	72.2% 13/18 • Number of events 38 • 2 years	83.3% 15/18 • Number of events 30 • 2 years
Gastrointestinal disorders gastrointestinal symptom	33.3% 6/18 • Number of events 9 • 2 years	27.8% 5/18 • Number of events 10 • 2 years
Musculoskeletal and connective tissue disorders musculoskeletal pain	38.9% 7/18 • Number of events 17 • 2 years	50.0% 9/18 • Number of events 23 • 2 years
General disorders urinary tract infection or pain	38.9% 7/18 • Number of events 12 • 2 years	50.0% 9/18 • Number of events 18 • 2 years

Additional Information

Dr. Sharon Moe

Indiana University School of Medicine

Phone: 317 278 2868

Email: smoe@iu.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place