Does Thiazolidinedione Therapy Improve Endothelial Function and Preserve Renal Function

• Sponsor: Mayo Clinic (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00586261
• Collaborator: (none)
• Enrollment: 36
• Location: 1
• Arms: 2
• Duration (Months): 40
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease	Drug: Pioglitazone; Drug: Placebo; Drug: Nitroglycerin	N/A

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Does Chronic Thiazolidinedione Therapy Improve Endothelial Function and Preserve Renal Function in Non-Diabetic Patients With Chronic Kidney Disease?
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo 30 mg daily for 6 months, nitroglycerin was given to check the brachial reactivity.	Drug: Placebo; Placebo 30 mg daily for 6 months; Drug: Nitroglycerin; 0.4 mg sublingual nitroglycerin tablet was given to all patients without a contraindication to check the brachial reactivity.; Other Names: Nitrostat
Active Comparator: Pioglitazone Pioglitazone 30 mg daily for 6 months, nitroglycerin was given to check the brachial reactivity.	Drug: Pioglitazone; Pioglitazone 30 mg daily for 6 months; Other Names: Actos ; Drug: Nitroglycerin; 0.4 mg sublingual nitroglycerin tablet was given to all patients without a contraindication to check the brachial reactivity.; Other Names: Nitrostat

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic

Investigators

• Principal Investigator: Patricia M. Best, M.D., Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

None provided.

• Responsible Party: Patricia J M Best, MD, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00586261
• Other Study ID Numbers: 06-002245
• First Posted: Jan 4, 2008
• Last Update Posted: Mar 15, 2013
• Last Verified: Mar 1, 2013

• Keywords provided by Patricia J M Best, MD, Mayo Clinic: Kidney Failure, Chronic; Renal Insufficiency, Chronic; Proteinuria; Albuminuria
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Pioglitazone; Nitroglycerin

Study Results

Participant Flow

Recruitment Details	Patients were recruited from the Mayo Clinic, Rochester, Minnesota.

Arm/Group Title	Pioglitazone	Placebo
Arm/Group Description	Pioglitazone 30 mg daily for 6 months	Placebo 30 mg daily for 6 months
Period Title: Overall Study
STARTED	17	19
COMPLETED	17	19
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Pioglitazone Arm	Placebo Arm	Total
Arm/Group Description	study the specific dose of pioglitazone 30 mg daily for 6 months pioglitazone : pioglitazone 30 mg daily for 6 months	study the specific dose of placebo 30 mg daily for 6 months placebo : placebo 30 mg daily for 6 months	Total of all reporting groups
Overall Participants	17	19	36
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 17.6%	4 21.1%	7 19.4%
>=65 years	14 82.4%	15 78.9%	29 80.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	74.2 (7.4)	72.1 (8.3)	73.1 (7.9)
Sex: Female, Male (Count of Participants)
Female	7 41.2%	9 47.4%	16 44.4%
Male	10 58.8%	10 52.6%	20 55.6%
Region of Enrollment (participants) [Number]
United States	17 100%	19 100%	36 100%

Outcome Measures

1. Primary Outcome

Title	Change in Brachial Arterial Reactivity
Description	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

Outcome Measure Data

Analysis Population Description

The study was stopped early due to low recruitment and no evidence of an effect in this analysis.

Arm/Group Title	Pioglitazone Arm	Placebo Arm
Arm/Group Description	study the specific dose of pioglitazone 30 mg daily for 6 months pioglitazone : pioglitazone 30 mg daily for 6 months	study the specific dose of placebo 30 mg daily for 6 months placebo : placebo 30 mg daily for 6 months
Measure Participants	17	19
Mean (Standard Error) [mm]	0.8476 (1.35)	2.6058 (1.35)

Adverse Events

Arm/Group Title	Pioglitazone		Placebo
Arm/Group Description	Pioglitazone 30 mg daily for six months		Placebo 30 mg daily for six months
All Cause Mortality
	Pioglitazone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pioglitazone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/17 (5.9%)		0/19 (0%)
Endocrine disorders
hypoglycemia	1/17 (5.9%)	1	0/19 (0%)	0
Other (Not Including Serious) Adverse Events
	Pioglitazone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/17 (5.9%)		0/19 (0%)
Vascular disorders
edema	1/17 (5.9%)	1	0/19 (0%)	0

Limitations/Caveats

The study was stopped early due to low enrollment because of the specifics of the inclusion criteria.

More Information

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.