Clinical trial NCT00105066: The Effects of Metformin on Blood Vessel Structure and Function
Official title: The Effects of Metformin on Vascular Structure and Function in Subjects With the Metabolic Syndrome (MET Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obesity
Hypertension
Hypercholesterolemia
Hyperglycemia
Keywords: Metabolic Syndrome
triglycerides
HDL
LDL
High Blood Pressure
High Cholesterol
High Blood Sugar
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2005-03-04
Enrollment: 77
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate whether the drug Metformin has beneficial effects on the blood vessels of individuals with the Metabolic Syndrome (MeS).

Detailed description: Individuals with the Metabolic Syndrome (MeS) are at increased risk for developing cardiovascular diseases. This increased risk may, in part, be related to abnormalities in the blood vessels. MeS is defined as having 3 or more of the following 5 criteria:

* Abdominal obesity (waist measurement \>39.8 inches in men, \>34.4 inches in women)
* Elevated triglycerides (\>150 mg/dl)
* Low HDL or "good" cholesterol (\<40 mg/dl in men or \<50 mg/dl in women)
* Elevated blood pressure (\>130/85) or treatment for high blood pressure
* Elevated fasting blood sugar (\>100 mg/dl)

Metformin is a medication that is approved by the Food and Drug Administration (FDA) for the treatment of diabetes; however, it can also be safely administered to non-diabetic subjects. We are evaluating whether Metformin reduces the stiffness of blood vessels and improves endothelial function.

This study requires 4 visits to the NIA Clinical Research Center (located on the premises of Harbor Hospital) over a 5-month period. At the initial visit, patients will be given a physical examination with blood and urine tests, and an EKG. They will be randomized into one of two groups; one group will receive Metformin (1700 mg per day), while the other group will receive a placebo. Participants will take the medication for 4 months. Subsequent visits will include additional blood tests, ultrasound and echo exams.

Taking part in this study is entirely voluntary. All testing and medications will be provided at no cost to the participant or their family.

Eligibility criteria: Inclusion Criteria:

Participants with the Metabolic Syndrome, which is defined as having 3 or more of the following 5 alterations:

* Abdominal obesity (waist measurement \>39.8 inches in men, \>34.4 inches in women)
* Elevated triglycerides (\>150 mg/dl)
* Low HDL or "good" cholesterol (\<40 mg/dl in men or \<50 mg/dl in women)
* Elevated blood pressure (\>130/85) or treatment for high blood pressure
* Elevated fasting blood sugar (\>100 mg/dl)

Exclusion Criteria:

* Diabetes treated with medication
* Blood pressure \>160/100 mmHg
* Clinical Congestive Heart Failure
* Anemia with hematocrit \<32%
* Asthma or Chronic Obstructive Pulmonary Disease (COPD) requiring daily medication or use of home oxygen therapy
* Major surgery planned within the next six months
* A recent, unexplained weight loss of \>10% of body weight in the past 6 months
* A known allergy or hypersensitivity to Metformin
* History of hepatitis or cirrhosis
* History of kidney disease (defined as serum creatinine \>1.4 mg/dL in men, \>1.3 mg/dL in women)
* Pregnancy or the absence of an effective method of contraception
* Illicit drug or alcohol abuse
* Cancer requiring treatment currently or recently completed treatment in the last 2 months

Primary outcomes:
measure: Change in Arterial Stiffness Compared to Baseline
timeFrame: Baseline and 4.5 months
measure: Change in Flow Mediated Dilation (FMD)
timeFrame: Baseline and 4.5 months
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: National Institute on Aging (NIA), Harbor Hospital
state: Maryland
Study officials:
affiliation: National Institute on Aging (NIA)
name: Luigi Ferrucci, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Institute on Aging (NIA)
name: James Strait, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403. doi: 10.1056/NEJMoa012512.
citation: Beisswenger PJ, Howell SK, Touchette AD, Lal S, Szwergold BS. Metformin reduces systemic methylglyoxal levels in type 2 diabetes. Diabetes. 1999 Jan;48(1):198-202. doi: 10.2337/diabetes.48.1.198.
citation: Mather KJ, Verma S, Anderson TJ. Improved endothelial function with metformin in type 2 diabetes mellitus. J Am Coll Cardiol. 2001 Apr;37(5):1344-50. doi: 10.1016/s0735-1097(01)01129-9.
citation: Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):854-65.