Effect of a Fibrate and a Statin on Endothelial Dysfunction

• Sponsor: Boston University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00491400
• Collaborator: (none)
• Enrollment: 28
• Location: 1
• Arms: 2
• Duration (Months): 39
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The study will compare the effect of atorvastatin to the effect of fenofibrate on endothelial function in patients with diabetes mellitus or the metabolic syndrome.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus; Metabolic Syndrome	Drug: Fenofibrate; Drug: Atorvastatin	N/A

Detailed Description

The study will compare the effect of atorvastatin to the effect of fenofibrate on endothelial function in patients with diabetes mellitus or the metabolic syndrome. The study is a double blind, placebo controlled, crossover study with the order of treatment randomized. Patients will receive each treatment for 8 weeks with a 1 week rest period between treatment periods. Endothelial function will be tested using non-invasive techniques before and after each treatments. A total of 40 subjects with diabetes or the metabolic syndrome will be enrolled at Boston Medical Center.

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Effect of a Fibrate (Fenofibrate) and a Statin (Atorvastatin) and on Endothelial Dysfunction in Diabetes Mellitus and the Metabolic Syndrome
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Fenofibrate First Fenofibrate 145 mg/day for 8 weeks First and Atorvastatin 20 mg/day for 8 weeks Second	Drug: Fenofibrate; 140 mg/day for 8 weeks; Other Names: Tricor ; Drug: Atorvastatin; 20 mg/day for 8 weeks; Other Names: Lipitor
Active Comparator: Atorvastatin First Atorvastatin 20 mg/day for 8 weeks First and Fenofibrate 145 mg/day for 8 weeks Second	Drug: Fenofibrate; 140 mg/day for 8 weeks; Other Names: Tricor ; Drug: Atorvastatin; 20 mg/day for 8 weeks; Other Names: Lipitor

Outcome Measures

Primary Outcome Measures

1. Brachial Artery Flow-mediated Dilation [8 weeks]

   Endothelial function was assessed as brachial artery flow-mediated dilation (FMD) using ultrasound. FMD is calculated as the difference in brachial diameter during hyperemic flow and brachial diameter at baseline divided by brachial diameter at baseline and expressed as percent dilation.

Secondary Outcome Measures

1. Serum Lipids [8 weeks]

   Effect of the intervention on total cholesterol, HDL, and triglycerides

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age greater than 30 years

• Adult-onset DM (defined as fasting glucose greater than 125 mg/dl or by ongoing treatment with an oral hypoglycemic agent) or metabolic syndrome (defined as at least 3 of the following: 1. HDL less than 40 mg/dl for men or less than 50 mg/dl for women;

1. triglycerides greater than 150 mg/dl; 3. waist circumference greater than 40 inches for men and greater than 35 inches for women; 4. fasting glucose greater than 100 mg/dl).

• LDL cholesterol level less than 140 mg/dl

• Able to provide informed consent and complete study procedures

Exclusion Criteria:

• Change in therapy for glucose control or blood pressure less than 1 month before entry

• Hemoglobin A1C greater than 8.0%.

• Renal insufficiency (serum creatinine greater than 1.6 mg/dl in men or 1.5 mg/dl in women.

• Any investigational drug less than 1 month before entry.

• Pregnancy (excluded by urine pregnancy test at study entry with ongoing use of reliable form of birth control) or lactation

• Liver function tests or serum creatinine kinase (CK) greater than 3 times upper limit of normal.

• Clinically evident major illnesses or other problem that would make participation inappropriate

• Clinical history of symptomatic cholelithiasis

• Patients with coronary artery disease, peripheral arterial disease, or cerebral vascular disease will not be enrolled if they are currently taking lipid-lowering therapy

• Patients taking more than 40 mg/day of atorvastatin will be excluded. There is no "ceiling" level for patients taking fibrates.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Boston Medical Center	Boston	Massachusetts	United States	02118

Sponsors and Collaborators

• Boston University

Investigators

• Principal Investigator: Joseph A Vita, MD, Boston University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Joseph A. Vita, Professor of Medicine, Boston University
• ClinicalTrials.gov Identifier: NCT00491400
• Other Study ID Numbers: H-23185
• First Posted: Jun 26, 2007
• Last Update Posted: Oct 24, 2012
• Last Verified: Sep 1, 2012

• Keywords provided by Joseph A. Vita, Professor of Medicine, Boston University: endothelium; obesity; diabetes mellitus; dyslipidemia
• Additional relevant MeSH terms: Diabetes Mellitus; Metabolic Syndrome; Syndrome; Atorvastatin; Fenofibrate

Study Results

Participant Flow

Recruitment Details	Patients meeting the entry criteria were recruited at Boston Medical Center.
Pre-assignment Detail	101 patients were consented and underwent screening. 73 were excluded because testing demonstrated that they were ineligible. 28 Entered the study 9 withdrew from the study

Arm/Group Title	Fenofibrate First	Atorvastatin First
Arm/Group Description	Participants randomized to receive fenofibrate first and atorvastatin second	Participants randomized to receive atorvastatin first and fenofibrate second
Period Title: Overall Study
STARTED	15	13
Started First Treatment	14	13
Completed First Treatment	14	9
Started Second Treatment	12	9
Finished Second Treatment	10	9
COMPLETED	10	9
NOT COMPLETED	5	4

Baseline Characteristics

Arm/Group Title	Fenofibrate First	Atorvastatin First	Total
Arm/Group Description	Fenofibrate First and Atorvastatin Second	Atorvastatin First and Fenofibrate Second	Total of all reporting groups
Overall Participants	15	13	28
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 100%	13 100%	28 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	10 66.7%	9 69.2%	19 67.9%
Male	5 33.3%	4 30.8%	9 32.1%
Region of Enrollment (participants) [Number]
United States	15 100%	13 100%	28 100%

Outcome Measures

1. Primary Outcome

Title	Brachial Artery Flow-mediated Dilation
Description	Endothelial function was assessed as brachial artery flow-mediated dilation (FMD) using ultrasound. FMD is calculated as the difference in brachial diameter during hyperemic flow and brachial diameter at baseline divided by brachial diameter at baseline and expressed as percent dilation.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

The number of participants is too few for meaningful analysis.

Arm/Group Title	Fenofibrate Treatment	Atorvastatin Treatment
Arm/Group Description	Effect of fenofibrate on brachial artery FMD	Effect of atorvastatin on brachial artery FMD
Measure Participants	0	0

2. Secondary Outcome

Title	Serum Lipids
Description	Effect of the intervention on total cholesterol, HDL, and triglycerides
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Enrollment was insufficient and there are too few subjects for meaningful analysis

Arm/Group Title	Fenofibrate	Atorvastatin
Arm/Group Description	Effect of fenofibrate treatment on lipid profile	Effect of atorvastatin treatment on lipid profile
Measure Participants	0	0

Adverse Events

Arm/Group Title	Fenofibrate First		Atorvastatin First
Arm/Group Description	Fenofibrate First and Atorvastatin Second		Atorvastatin First and Fenofibrate Second
All Cause Mortality
	Fenofibrate First		Atorvastatin First
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Fenofibrate First		Atorvastatin First
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Fenofibrate First		Atorvastatin First
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/13 (0%)

Limitations/Caveats

Early termination due to inadequate enrollment

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.