The Effects of Metformin on Blood Vessel Structure and Function

• Sponsor: National Institute on Aging (NIA) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00105066
• Collaborator: (none)
• Enrollment: 77
• Location: 1
• Arms: 2
• Duration (Months): 52
• Patients Per Site Per Month: 1.5

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Obesity; Hypertension; Hypercholesterolemia; Hyperglycemia	Drug: Metformin; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 77 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Effects of Metformin on Vascular Structure and Function in Subjects With the Metabolic Syndrome (MET Trial)
• Study Start Date: Jan 1, 2004
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: May 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo placebo	Drug: Placebo; placebo tablet once a day for one month, then twice a day for 3 months
Experimental: Metformin Metformin 850 mg twice daily	Drug: Metformin; 850mg tablet once a day for one month, then twice a day for 3 months; Other Names: Fortamet®; Glucophage®; Glumetza™; Riomet™

Outcome Measures

Primary Outcome Measures

1. Change in Arterial Stiffness Compared to Baseline [Baseline and 4.5 months]

2. Change in Flow Mediated Dilation (FMD) [Baseline and 4.5 months]

   to evaluate improvement in endothelial function

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institute on Aging (NIA), Harbor Hospital	Baltimore	Maryland	United States	21225

Sponsors and Collaborators

• National Institute on Aging (NIA)

Investigators

• Principal Investigator: Luigi Ferrucci, MD, National Institute on Aging (NIA)
• Principal Investigator: James Strait, M.D., Ph.D., National Institute on Aging (NIA)

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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. Erratum in: Lancet 1998 Nov 7;352(9139):1558.
• 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.
• 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.

• Responsible Party: National Institute on Aging (NIA)
• ClinicalTrials.gov Identifier: NCT00105066
• Other Study ID Numbers: AG0017
• First Posted: Mar 4, 2005
• Last Update Posted: Jan 18, 2017
• Last Verified: Jan 1, 2017

• Keywords provided by National Institute on Aging (NIA): Metabolic Syndrome; triglycerides; HDL; LDL; High Blood Pressure; High Cholesterol; High Blood Sugar
• Additional relevant MeSH terms: Hypercholesterolemia; Hyperglycemia; Metformin

Study Results

Participant Flow

Arm/Group Title	Placebo	Metformin
Arm/Group Description	Placebo : placebo tablet once a day for one month, then twice a day for 3 months	Metformin : 850mg tablet once a day for one month, then twice a day for 3 months
Period Title: Overall Study
STARTED	27	50
COMPLETED	25	45
NOT COMPLETED	2	5

Baseline Characteristics

Arm/Group Title	Placebo	Metformin	Total
Arm/Group Description	Placebo : placebo tablet once a day for one month, then twice a day for 3 months	Metformin : 850mg tablet once a day for one month, then twice a day for 3 months	Total of all reporting groups
Overall Participants	27	49	76
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.6 (13.5)	55.1 (11.8)	54.4 (12.7)
Gender (Count of Participants)
Female	19 70.4%	34 69.4%	53 69.7%
Male	8 29.6%	15 30.6%	23 30.3%
Carotid Femoral Pulse Wave Velocity (meters/second) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [meters/second]	6.8 (2.1)	6.8 (2.1)	6.8 (2.1)
FMD (percentage) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage]	7.6 (4.4)	9.3 (6.1)	8.5 (5.3)
HOMA-S (HOMA Score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [HOMA Score]	52.9 (26.9)	52.3 (23.1)	52.5 (24.5)

Outcome Measures

1. Primary Outcome

Title	Change in Arterial Stiffness Compared to Baseline
Time Frame	Baseline and 4.5 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Metformin
Arm/Group Description	Placebo : placebo tablet once a day for one month, then twice a day for 3 months	Metformin : 850mg tablet once a day for one month, then twice a day for 3 months
Measure Participants	25	45
Mean (Standard Deviation) [meters / second]	-7.2 (2.1)	-7.3 (1.8)

2. Primary Outcome

Title	Change in Flow Mediated Dilation (FMD)
Description	to evaluate improvement in endothelial function
Time Frame	Baseline and 4.5 months

Outcome Measure Data

Analysis Population Description

Participants with complete data.

Arm/Group Title	Placebo	Metformin
Arm/Group Description	Placebo : placebo tablet once a day for one month, then twice a day for 3 months	Metformin : 850mg tablet once a day for one month, then twice a day for 3 months
Measure Participants	23	39
Mean (Standard Deviation) [percentage change in diameter]	8.8 (7.0)	10.5 (8.0)

3. Post-Hoc Outcome

Title	Homa Insulin Sensitivity
Description	Homeostatic Model Assessment of insulin sensitivity
Time Frame	4.5 months

Outcome Measure Data

Analysis Population Description

Participants with complete data.

Arm/Group Title	Placebo	Metformin
Arm/Group Description	Placebo : placebo tablet once a day for one month, then twice a day for 3 months	Metformin : 850mg tablet once a day for one month, then twice a day for 3 months
Measure Participants	23	39
Mean (Standard Deviation) [HOMA Score]	57.4 (36.3)	64.5 (27.7)

Adverse Events

Arm/Group Title	Placebo		Metformin
Arm/Group Description	Placebo : placebo tablet once a day for one month, then twice a day for 3 months		Metformin : 850mg tablet once a day for one month, then twice a day for 3 months
All Cause Mortality
	Placebo		Metformin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Metformin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/50 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Metformin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/27 (3.7%)		6/50 (12%)
Gastrointestinal disorders
Nausea	1/27 (3.7%)	1	6/50 (12%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.