Metabolic SyndromeEJB044NCT02633488
Effect of Metformin on Insulin Sensitivity and Pan-Arterial Vascular Function in Adults With Metabolic Syndrome
A study testing metformin in people with Metabolic Syndrome and Insulin Sensitivity, run by University of Virginia at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Metabolic Syndrome, Insulin Sensitivity
- What is being tested?
- metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2014to Jul 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Show all 15Show fewer
- 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
Who cannot join
- 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.
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia
Charlottesville, Virginia, 22903
About this study
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.
Read the 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.
- Conditions
- Metabolic Syndrome, Insulin Sensitivity
- Being tested
- Placebos, metformin
- Medical subject headings
- Metabolic Syndrome, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlacebosDrug
Also called inactive substance
A 12 week single blind placebos
metforminDrug
Also called glucophage
A 12 week single blind metformin
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 12 weeks of Placebo tablet 3 x daily Receives: Drug: Placebos |
| Metformin | Experimental | 12 weeks of Metformin tablet 850 mg 3 x daily Receives: Drug: metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Flow Mediated Dilation - Endothelial Function
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
Measured: before and after 12 weeks on placebo or metformin
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2015 (estimated)
- Study startJun 2014
- Primary completionJul 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (45)Papers the sponsor has linked to this study.
- Other trials for Metabolic SyndromeStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Eugene Barrett, University of Virginia
- Investigators
- Eugene Barett, MD, PhD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02633488
- Sponsor's protocol ID
- 16121
- Acronym
- EJB044
- Status last verified
- Mar 2020
- First submitted
- 26 Sep 2014
- Last updated
- 23 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: Data will be reported as composite for the entire population. In some figures individual data point are displayed but not identified with individual subjects.
Publications
ACCORD Study Group; Cushman WC, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr, Cutler JA, Simons-Morton DG, Basile JN, Corson MA, Probstfield JL, Katz L, Peterson KA, Friedewald WT, Buse JB, Bigger JT, Gerstein HC, Ismail-Beigi F. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010 Apr 29;362(17):1575-85. doi: 10.1056/NEJMoa1001286. Epub 2010 Mar 14.
PubMed 20228401Brown A, Reynolds LR, Bruemmer D. Intensive glycemic control and cardiovascular disease: an update. Nat Rev Cardiol. 2010 Jul;7(7):369-75. doi: 10.1038/nrcardio.2010.35. Epub 2010 Apr 20.
PubMed 20404853Cooper-DeHoff RM, Gong Y, Handberg EM, Bavry AA, Denardo SJ, Bakris GL, Pepine CJ. Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease. JAMA. 2010 Jul 7;304(1):61-8. doi: 10.1001/jama.2010.884.
PubMed 20606150Steinberg HO, Paradisi G, Hook G, Crowder K, Cronin J, Baron AD. Free fatty acid elevation impairs insulin-mediated vasodilation and nitric oxide production. Diabetes. 2000 Jul;49(7):1231-8. doi: 10.2337/diabetes.49.7.1231.
PubMed 10909983Steinberg HO, Tarshoby M, Monestel R, Hook G, Cronin J, Johnson A, Bayazeed B, Baron AD. Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. J Clin Invest. 1997 Sep 1;100(5):1230-9. doi: 10.1172/JCI119636.
PubMed 9276741Tripathy D, Mohanty P, Dhindsa S, Syed T, Ghanim H, Aljada A, Dandona P. Elevation of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects. Diabetes. 2003 Dec;52(12):2882-7. doi: 10.2337/diabetes.52.12.2882.
PubMed 14633847de Jongh RT, Serne EH, Ijzerman RG, de Vries G, Stehouwer CD. Free fatty acid levels modulate microvascular function: relevance for obesity-associated insulin resistance, hypertension, and microangiopathy. Diabetes. 2004 Nov;53(11):2873-82. doi: 10.2337/diabetes.53.11.2873.
PubMed 15504968Liu Z, Liu J, Jahn LA, Fowler DE, Barrett EJ. Infusing lipid raises plasma free fatty acids and induces insulin resistance in muscle microvasculature. J Clin Endocrinol Metab. 2009 Sep;94(9):3543-9. doi: 10.1210/jc.2009-0027. Epub 2009 Jun 30.
PubMed 19567533Westerbacka J, Seppala-Lindroos A, Yki-Jarvinen H. Resistance to acute insulin induced decreases in large artery stiffness accompanies the insulin resistance syndrome. J Clin Endocrinol Metab. 2001 Nov;86(11):5262-8. doi: 10.1210/jcem.86.11.8047.
PubMed 11701689Westerbacka J, Vehkavaara S, Bergholm R, Wilkinson I, Cockcroft J, Yki-Jarvinen H. Marked resistance of the ability of insulin to decrease arterial stiffness characterizes human obesity. Diabetes. 1999 Apr;48(4):821-7. doi: 10.2337/diabetes.48.4.821.
PubMed 10102699Baron AD, Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G. Insulin-mediated skeletal muscle vasodilation contributes to both insulin sensitivity and responsiveness in lean humans. J Clin Invest. 1995 Aug;96(2):786-92. doi: 10.1172/JCI118124.
PubMed 7635973Barrett EJ, Eggleston EM, Inyard AC, Wang H, Li G, Chai W, Liu Z. The vascular actions of insulin control its delivery to muscle and regulate the rate-limiting step in skeletal muscle insulin action. Diabetologia. 2009 May;52(5):752-64. doi: 10.1007/s00125-009-1313-z. Epub 2009 Mar 13.
PubMed 19283361Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G, Baron AD. Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Invest. 1996 Jun 1;97(11):2601-10. doi: 10.1172/JCI118709.
PubMed 8647954Rossi R, Cioni E, Nuzzo A, Origliani G, Modena MG. Endothelial-dependent vasodilation and incidence of type 2 diabetes in a population of healthy postmenopausal women. Diabetes Care. 2005 Mar;28(3):702-7. doi: 10.2337/diacare.28.3.702.
PubMed 15735211Goldfine AB, Beckman JA, Betensky RA, Devlin H, Hurley S, Varo N, Schonbeck U, Patti ME, Creager MA. Family history of diabetes is a major determinant of endothelial function. J Am Coll Cardiol. 2006 Jun 20;47(12):2456-61. doi: 10.1016/j.jacc.2006.02.045. Epub 2006 May 30.
PubMed 16781373
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Metformin on Insulin Sensitivity and Pan-Arterial Vascular Function in Adults With Metabolic Syndrome
- ClinicalTrials.gov ID
- NCT02633488
- Acronym / sponsor ID
- EJB044 / 16121
- Conditions
- Metabolic Syndrome, Insulin Sensitivity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Study start
- Jun 2014
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 17 Dec 2015 (estimated)
- Results
- Posted 23 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebos12 weeks of Placebo tablet 3 x daily |
| Metformin | Experimental | Drug: metformin12 weeks of Metformin tablet 850 mg 3 x daily |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Age 18-60
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlacebosAlso: inactive substanceA 12 week single blind placebos | Drug | Placebo |
| metforminAlso: glucophageA 12 week single blind metformin | Drug | Metformin |
Primary outcome
Flow Mediated Dilation - Endothelial Function
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20228401ACCORD Study Group; Cushman WC, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr, Cutler JA, Simons-Morton DG, Basile JN, Corson MA, Probstfield JL, Katz L, Peterson KA, Friedewald WT, Buse JB, Bigger JT, Gerstein HC, Ismail-Beigi F. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010 Apr 29;362(17):1575-85. doi: 10.1056/NEJMoa1001286. Epub 2010 Mar 14.
- Background: PubMed 20404853Brown A, Reynolds LR, Bruemmer D. Intensive glycemic control and cardiovascular disease: an update. Nat Rev Cardiol. 2010 Jul;7(7):369-75. doi: 10.1038/nrcardio.2010.35. Epub 2010 Apr 20.
- Background: PubMed 20606150Cooper-DeHoff RM, Gong Y, Handberg EM, Bavry AA, Denardo SJ, Bakris GL, Pepine CJ. Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease. JAMA. 2010 Jul 7;304(1):61-8. doi: 10.1001/jama.2010.884.
- Background: PubMed 10909983Steinberg HO, Paradisi G, Hook G, Crowder K, Cronin J, Baron AD. Free fatty acid elevation impairs insulin-mediated vasodilation and nitric oxide production. Diabetes. 2000 Jul;49(7):1231-8. doi: 10.2337/diabetes.49.7.1231.
- Background: PubMed 9276741Steinberg HO, Tarshoby M, Monestel R, Hook G, Cronin J, Johnson A, Bayazeed B, Baron AD. Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. J Clin Invest. 1997 Sep 1;100(5):1230-9. doi: 10.1172/JCI119636.
- Background: PubMed 14633847Tripathy D, Mohanty P, Dhindsa S, Syed T, Ghanim H, Aljada A, Dandona P. Elevation of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects. Diabetes. 2003 Dec;52(12):2882-7. doi: 10.2337/diabetes.52.12.2882.
- Background: PubMed 15504968de Jongh RT, Serne EH, Ijzerman RG, de Vries G, Stehouwer CD. Free fatty acid levels modulate microvascular function: relevance for obesity-associated insulin resistance, hypertension, and microangiopathy. Diabetes. 2004 Nov;53(11):2873-82. doi: 10.2337/diabetes.53.11.2873.
- Background: PubMed 19567533Liu Z, Liu J, Jahn LA, Fowler DE, Barrett EJ. Infusing lipid raises plasma free fatty acids and induces insulin resistance in muscle microvasculature. J Clin Endocrinol Metab. 2009 Sep;94(9):3543-9. doi: 10.1210/jc.2009-0027. Epub 2009 Jun 30.
- Background: PubMed 11701689Westerbacka J, Seppala-Lindroos A, Yki-Jarvinen H. Resistance to acute insulin induced decreases in large artery stiffness accompanies the insulin resistance syndrome. J Clin Endocrinol Metab. 2001 Nov;86(11):5262-8. doi: 10.1210/jcem.86.11.8047.
- Background: PubMed 10102699Westerbacka J, Vehkavaara S, Bergholm R, Wilkinson I, Cockcroft J, Yki-Jarvinen H. Marked resistance of the ability of insulin to decrease arterial stiffness characterizes human obesity. Diabetes. 1999 Apr;48(4):821-7. doi: 10.2337/diabetes.48.4.821.
- Background: PubMed 7635973Baron AD, Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G. Insulin-mediated skeletal muscle vasodilation contributes to both insulin sensitivity and responsiveness in lean humans. J Clin Invest. 1995 Aug;96(2):786-92. doi: 10.1172/JCI118124.
- Background: PubMed 19283361Barrett EJ, Eggleston EM, Inyard AC, Wang H, Li G, Chai W, Liu Z. The vascular actions of insulin control its delivery to muscle and regulate the rate-limiting step in skeletal muscle insulin action. Diabetologia. 2009 May;52(5):752-64. doi: 10.1007/s00125-009-1313-z. Epub 2009 Mar 13.
- Individual participant dataSharing planned: No. Data will be reported as composite for the entire population. In some figures individual data point are displayed but not identified with individual subjects.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eugene Barett, MD, PhD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing metformin in people with Metabolic Syndrome and Insulin Sensitivity, run by University of Virginia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Flow Mediated Dilation - Endothelial Function (time frame: before and after 12 weeks on placebo or metformin). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02633488, which also lists 45 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2020.