Chronic Kidney Disease
Conditions
Keywords
Kidney Failure, Chronic, Renal Insufficiency, Chronic, Proteinuria, Albuminuria
Brief summary
The hypothesis of the current proposal is that chronic pioglitazone therapy will result in improved endothelial function, decreased inflammation, and preservation of renal function in patients with CKD but without diabetes.
Detailed description
Despite continued improvements in the outcomes of patients with cardiovascular disease, similar improvements have not been seen in patients with chronic kidney disease (CKD). CKD constitutes one of the highest risk populations for cardiovascular disease. When the creatinine clearance is ≤ 60 ml/min the risk for cardiovascular events is greater than that of diabetes. However, few studies have focused on the prevention or treatment of coronary artery disease (CAD) in CKD patients. The development of endothelial dysfunction and increased inflammation appear to be critical in the development of atherosclerosis and cardiovascular disease. The broad long-term objective of this grant proposal is to determine unique therapies to reduce endothelial dysfunction and inflammation, and thereby help to prevent cardiovascular disease and preserve renal function in patients with CKD. Thiazolidinediones such as pioglitazone appear to improve endothelial function and decrease inflammation, an effect that may be present in patients with or without diabetes. To address this hypothesis the following Specific Aims are proposed: 1. To determine the effects of chronic pioglitazone therapy on endothelial function in non-diabetic patients with CKD (creatinine clearance ≤ 60 ml/ min, but not on dialysis) 2. To determine the effects chronic pioglitazone therapy on inflammation and oxidative stress in non-diabetic patients with CKD 3. To determine the effects chronic pioglitazone therapy on progression of renal disease in non-diabetic patients with CKD
Interventions
DRUGPioglitazone
Pioglitazone 30 mg daily for 6 months
DRUGPlacebo
Placebo 30 mg daily for 6 months
DRUGNitroglycerin
0.4 mg sublingual nitroglycerin tablet was given to all patients without a contraindication to check the brachial reactivity.
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age over 18 years. * Creatinine clearance ≤ 60 ml/min by the Cockcroft-Gault equation * Patients not anticipated to go on dialysis or have renal transplantation in the next 6 months * Ability to provide informed consent * Life expectancy greater than 12 months
Exclusion criteria
* Diabetes mellitus or a fasting blood glucose ≥ 110 mg/dL * Acute renal failure * Class 3 or 4 heart failure * Liver failure, ascites, or an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) two times the upper limit of normal * Hemoglobin less than 9 mg/dL * Multiple myeloma * Premenopausal women not using at least 1 form of birth control * Pregnant or nursing women * Prisoners * Known allergy to pioglitazone
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Brachial Arterial Reactivity | After 6 months of treatment | Brachial arterial reactivity was measured by ultrasound. A blood pressure cuff was placed around the right forearm. Using the ultrasound probe of the ultrasound, 2-dimensional images clearly defining the anterior and posterior intimal wall of the brachial artery were collected. Flow velocities were then measured using pulsed wave Doppler. The blood pressure cuff previously placed around the patient's right forearm was inflated to 200 mmHg. The cuff remained inflated for 5 minutes as the patient remained motionless and quiet. Prior to deflation, the patient was asked to remain still as flow velocities and 2-dimensional images were obtained immediately following cuff deflation. Then a 0.4 mg sublingual nitroglycerin tablet was given to all patients without a contraindication and all measurements were repeated. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from the Mayo Clinic, Rochester, Minnesota.
Participants by arm
| Arm | Count |
|---|---|
| Pioglitazone Arm study the specific dose of pioglitazone 30 mg daily for 6 months
pioglitazone : pioglitazone 30 mg daily for 6 months | 17 |
| Placebo Arm study the specific dose of placebo 30 mg daily for 6 months
placebo : placebo 30 mg daily for 6 months | 19 |
| Total | 36 |
Baseline characteristics
| Characteristic | Placebo Arm | Pioglitazone Arm | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 15 Participants | 14 Participants | 29 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 3 Participants | 7 Participants |
| Age Continuous | 72.1 years STANDARD_DEVIATION 8.3 | 74.2 years STANDARD_DEVIATION 7.4 | 73.1 years STANDARD_DEVIATION 7.9 |
| Region of Enrollment United States | 19 participants | 17 participants | 36 participants |
| Sex: Female, Male Female | 9 Participants | 7 Participants | 16 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 17 | 0 / 19 |
| serious Total, serious adverse events | 1 / 17 | 0 / 19 |
Outcome results
Primary
Change in Brachial Arterial Reactivity
Brachial arterial reactivity was measured by ultrasound. A blood pressure cuff was placed around the right forearm. Using the ultrasound probe of the ultrasound, 2-dimensional images clearly defining the anterior and posterior intimal wall of the brachial artery were collected. Flow velocities were then measured using pulsed wave Doppler. The blood pressure cuff previously placed around the patient's right forearm was inflated to 200 mmHg. The cuff remained inflated for 5 minutes as the patient remained motionless and quiet. Prior to deflation, the patient was asked to remain still as flow velocities and 2-dimensional images were obtained immediately following cuff deflation. Then a 0.4 mg sublingual nitroglycerin tablet was given to all patients without a contraindication and all measurements were repeated.
Time frame: After 6 months of treatment
Population: The study was stopped early due to low recruitment and no evidence of an effect in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Arm | Change in Brachial Arterial Reactivity | 0.8476 mm | Standard Error 1.35 |
| Placebo Arm | Change in Brachial Arterial Reactivity | 2.6058 mm | Standard Error 1.35 |