Clincosm LogoSign in Get a demo

EJB044: Effect of Metformin on Insulin Sensitivity and Pan-Arterial Vascular Function in Adults With Metabolic Syndrome

Sponsor
University of Virginia (Other)
Overall Status
Completed
CT.gov ID
NCT02633488
Collaborator
(none)
19
Enrollment
1
Location
2
Arms
25
Duration (Months)
0.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to look at how insulin (a hormone that helps the cells get energy from sugar) in our body affects blood vessels (elasticity in the bigger blood vessels and blood flow in the smaller blood vessels in the arm) and how Metformin (a drug that makes you more sensitive to insulin) affects insulin's action on the blood vessels.

Condition or Disease Intervention/Treatment Phase
N/A

Detailed Description

In our protocol, we will study vascular function using pulse wave velocity (PWV) augmentation index (AI), flow mediated dilation (FMD) and contrast enhanced ultrasound (CEU) as well as insulin sensitivity (euglycemic clamp) in 50 adults with metabolic syndrome, age 18-60 years. They will each be studied 4 times,before and after two 12-wk interventions (randomly assigned) as follows: 1) Placebos and 2) Metformin . This is a cross-over design.

Study Design

Study Type:
Interventional
Actual Enrollment :
19 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Single (Participant)
Primary Purpose:
Treatment
Official Title:
Effect of Metformin on Insulin Sensitivity and Pan-Arterial Vascular Function in Adults With Metabolic Syndrome
Study Start Date :
Jun 1, 2014
Actual Primary Completion Date :
Jul 1, 2016
Actual Study Completion Date :
Jul 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

12 weeks of Placebo tablet 3 x daily

Drug: Placebos
A 12 week single blind placebos
Other Names:
  • inactive substance

    		•
    Experimental: Metformin

    12 weeks of Metformin tablet 850 mg 3 x daily

    Drug: metformin
    A 12 week single blind metformin
    Other Names:
  • glucophage

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Flow Mediated Dilation - Endothelial Function [before and after 12 weeks on placebo or metformin]

      brachial artery ultrasonography % flow-mediated dilatation (FMD) for assessing endothelial function before and after an insulin clamp to assess insulin's effect on the vasculature

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Age 18-60

    • No smoking the past 6 months

    • Normal screening labs or no clinically significant values-except those listed below

    • Must have 3 of the following 4 characteristics established by NCEP-AHA-NHLBI

    • Males waist circumference greater than 40 inches, females greater than 35 inches

    • Blood pressure greater than 130/85 or on treatment with one or more antihypertensive agent

    • Fasting plasma triglycerides >150 or HDL <40 (males) <50 (females)

    • Fasting blood sugar >100 but <126

    • Subject may participate if on the following drugs, provided the drugs can remain at stable doses throughout the 12 week treatment interval.

    • Ace inhibitor

    • ARB

    • HMG CoA reductase inhibitor

    • Beta blocker

    • Calcium channel blockers

    • Alpha-adrenergic antagonist

    Exclusion Criteria:

    • Smoking presently or in the past 6 months

    • HbA1c ≥ 6.5

    • Glucocorticoids-eg: prednisone, dexamethasone

    • Any known sensitivity or intolerance to Metformin

    • Any chronic GI disorders such as Irritable Bowel Syndrome or Crohns disease

    • History of congestive heart failure, ischemic heart disease, severe pulmonary disease, liver or kidney disease.

    • History of malignant or metabolic disorders including diabetes

    • Presence of an intracardiac or intrapulmonary shunt (we will screen for this by auscultation during the physical exam by PI)

    • Hypersensitivity to perflutren (contained in Definity)

    • Pregnant or breastfeeding

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Virginia Charlottesville Virginia United States 22903

    Sponsors and Collaborators

    • University of Virginia

    Investigators

    • Principal Investigator: Eugene Barett, MD, PhD, University of Virginia

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Eugene Barrett, MD PhD, University of Virginia
    ClinicalTrials.gov Identifier:
    NCT02633488
    Other Study ID Numbers:
    • 16121
    First Posted:
    Dec 17, 2015
    Last Update Posted:
    Mar 23, 2020
    Last Verified:
    Mar 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Additional relevant MeSH terms:
    Metabolic Syndrome
    Insulin Resistance
    Hypersensitivity
    Syndrome
    Metformin

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 6 subjects failed the screening. 2 subjects voluntarily withdrew.
    Arm/Group Title Placebo, Then Metformin Metformin, Then Placebo
    Arm/Group Description 12 weeks of Placebo tablet 3 x daily then 8 week washout then 12 weeks of metformin 500 mg 3x daily 12 weeks of metformin 500 mg tablet 3 x daily then 8 week washout then 12 weeks of placebo 3x daily
    Period Title: Overall Study
    STARTED 6 5
    COMPLETED 6 5
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Placebo, Then Metformin Metformin, Then Placebo Total
    Arm/Group Description 12 weeks of Placebo tablet 3 x daily, then a 8 week washout, then 12 weeks Metformin tablet 3 X daily 12 weeks of Metformin tablet 850 mg 3 x daily, then 8 week washout , then 12 weeks Placebo tablet 3X daily Total of all reporting groups
    Overall Participants 6 5 11
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    6
    100%
    5
    100%
    11
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    3
    50%
    3
    60%
    6
    54.5%
    Male
    3
    50%
    2
    40%
    5
    45.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    6
    100%
    5
    100%
    11
    100%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    2
    33.3%
    0
    0%
    2
    18.2%
    White
    4
    66.7%
    5
    100%
    9
    81.8%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    6
    100%
    5
    100%
    11
    100%

    Outcome Measures

    1. Primary Outcome
    Title Flow Mediated Dilation - Endothelial Function
    Description brachial artery ultrasonography % flow-mediated dilatation (FMD) for assessing endothelial function before and after an insulin clamp to assess insulin's effect on the vasculature
    Time Frame before and after 12 weeks on placebo or metformin

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pre and Post Placebo 12 Weeks Pre and Post Metformin 12 Weeks
    Arm/Group Description measured % dilation in response to shear stress before and after 2 hour insulin clamp which is performed before and after 12 weeks of Placebo tablets 3X daily measured % dilation in response to shear stress before and after 2 hour insulin clamp which is performed before and after 12 weeks of Metformin tablets 3X daily
    Measure Participants 11 11
    Mean (Standard Error) [percentage of artery dilation]
    6.1
    (1.1)
    6.2
    (1.1)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pre and Post Placebo 12 Weeks, Pre and Post Metformin 12 Weeks
    Comments
    Type of Statistical Test Equivalence
    Comments equivalence defined as less that 2 SD in FMD between 2 treatments
    Statistical Test of Hypothesis p-Value >0.05
    Comments FMD % change exceeded the threshold of our statistical significance test, i.e. the null hypothesis that there was no effect of metformin remained tenable.
    Method t-test, 2 sided
    Comments

    Adverse Events

    Time Frame 32 weeks
    Adverse Event Reporting Description
    Arm/Group Title Placebo Metformin
    Arm/Group Description 12 weeks of Placebo tablet 3 x daily Placebos: A 12 week single blind placebos 12 weeks of Metformin tablet 850 mg 3 x daily metformin: A 12 week single blind metformin
    All Cause Mortality
    Placebo Metformin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/11 (0%) 0/11 (0%)
    Serious Adverse Events
    Placebo Metformin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/11 (0%) 0/11 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo Metformin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/11 (0%) 0/11 (0%)

    Limitations/Caveats

    [Not Specified]

    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.

    Results Point of Contact

    Name/Title Eugene J. Barrett MD PhD
    Organization University of Virginia
    Phone 434-924-1263
    Email ejb8x@virginia.edu
    Responsible Party:
    Eugene Barrett, MD PhD, University of Virginia
    ClinicalTrials.gov Identifier:
    NCT02633488
    Other Study ID Numbers:
    • 16121
    First Posted:
    Dec 17, 2015
    Last Update Posted:
    Mar 23, 2020
    Last Verified:
    Mar 1, 2020