Hypercholesterolemia, Hyperglycemia, Hypertension, Obesity
Conditions
Keywords
Metabolic Syndrome, triglycerides, HDL, LDL, High Blood Pressure, High Cholesterol, High Blood Sugar
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.
Interventions
DRUGMetformin
850mg tablet once a day for one month, then twice a day for 3 months
DRUGPlacebo
placebo tablet once a day for one month, then twice a day for 3 months
Sponsors
National Institute on Aging (NIA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Arterial Stiffness Compared to Baseline | Baseline and 4.5 months | — |
| Change in Flow Mediated Dilation (FMD) | Baseline and 4.5 months | to evaluate improvement in endothelial function |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo : placebo tablet once a day for one month, then twice a day for 3 months | 27 |
| Metformin Metformin : 850mg tablet once a day for one month, then twice a day for 3 months | 49 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 5 |
Baseline characteristics
| Characteristic | Placebo | Metformin | Total |
|---|---|---|---|
| Age, Continuous | 53.6 years STANDARD_DEVIATION 13.5 | 55.1 years STANDARD_DEVIATION 11.8 | 54.4 years STANDARD_DEVIATION 12.7 |
| Carotid Femoral Pulse Wave Velocity | 6.8 meters/second STANDARD_DEVIATION 2.1 | 6.8 meters/second STANDARD_DEVIATION 2.1 | 6.8 meters/second STANDARD_DEVIATION 2.1 |
| FMD | 7.6 percentage STANDARD_DEVIATION 4.4 | 9.3 percentage STANDARD_DEVIATION 6.1 | 8.5 percentage STANDARD_DEVIATION 5.3 |
| Gender Female | 19 Participants | 34 Participants | 53 Participants |
| Gender Male | 8 Participants | 15 Participants | 23 Participants |
| HOMA-S | 52.9 HOMA Score STANDARD_DEVIATION 26.9 | 52.3 HOMA Score STANDARD_DEVIATION 23.1 | 52.5 HOMA Score STANDARD_DEVIATION 24.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 27 | 6 / 50 |
| serious Total, serious adverse events | 0 / 27 | 0 / 50 |
Outcome results
Primary
Change in Arterial Stiffness Compared to Baseline
Time frame: Baseline and 4.5 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Arterial Stiffness Compared to Baseline | -7.2 meters / second | Standard Deviation 2.1 |
| Metformin | Change in Arterial Stiffness Compared to Baseline | -7.3 meters / second | Standard Deviation 1.8 |
Primary
Change in Flow Mediated Dilation (FMD)
to evaluate improvement in endothelial function
Time frame: Baseline and 4.5 months
Population: Participants with complete data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Flow Mediated Dilation (FMD) | 8.8 percentage change in diameter | Standard Deviation 7 |
| Metformin | Change in Flow Mediated Dilation (FMD) | 10.5 percentage change in diameter | Standard Deviation 8 |
Post Hoc
Homa Insulin Sensitivity
Homeostatic Model Assessment of insulin sensitivity
Time frame: 4.5 months
Population: Participants with complete data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Homa Insulin Sensitivity | 57.4 HOMA Score | Standard Deviation 36.3 |
| Metformin | Homa Insulin Sensitivity | 64.5 HOMA Score | Standard Deviation 27.7 |