Metabolic SyndromePhase 2/3NCT03355469
Exercise Dose and Metformin for Vascular Health in Metabolic Syndrome
A Phase 2/3 study testing Metformin, Low Intensity Exercise and High Intensity Exercise in people with Metabolic Syndrome, run by Rutgers University at 1 site in United States.
Trial summary
Health organizations recommend exercise in an intensity based manner to promote cardiovascular adaptation and prevent disease. Metformin is a common anti-diabetes medication that reduces future type 2 diabetes and cardiovascular disease (CVD) risk. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Metabolic Syndrome
- What is being tested?
- Metformin, Low Intensity Exercise and High Intensity Exercise
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 91 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Aug 2017to 23 May 2024
- Phase
- Phase 2/3
- 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 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female ≥40 and ≤80 years old.
- Has a body mass index ≥25 and ≤47 kg/m2.
- Not diagnosed with Type 2 or Type 1 diabetes
- Not currently engaged in > 150 min/wk of exercise
- Weight stable (<2kg weight change in past 3 months)
- Non-smoking >5 years
Show all 22Show fewer
- At minimum, subject will have abdominal obesity (increased waist circumference as defined below) and may have any additional National Cholesterol Education Adult Treatment Panel III Metabolic Syndrome criteria:
- Increased waist circumference (≥102 cm in men; ≥88 cm in women)
- Elevated triglycerides (≥150 mg/dl), or on medication for treating the condition
- Reduced HDL-cholesterol (<40mg/dl in men, <50 mg/dl in women), or on medication for treating the condition
- High blood pressure (≥130 mmHg systolic or ≥85mmHg diastolic), or on medication for treating the condition
- Elevated fasting glucose (≥100 mg/dl), or on medication for treating the condition
- Other major risk factors to be noted based on the Framingham Risk Score
- HbA1c 5.7-6.4%
- LDL > 130 mg/dL
- Family history of type 2 diabetes (immediate family, i.e. parent/sibling)
- History of gestational diabetes
- History of Polycystic Ovarian Syndrome
- Family history of pre-mature cardiovascular disease (immediate family i.e. parent/sibling) before 55 for males or 65 for females that can include heart attack, peripheral arterial disease, abdominal aortic aneurysm, symptomatic carotid artery disease or clinical coronary heart disease)
- Age ( > 45 years old for men; > 55 years old for women)
- Black/African American, Mexican, Asian, and/or Hispanic
- Subjects currently taking medications that affect heart rate and rhythm (i.e. Ca++ channel blockers, nitrates, alpha- or beta-blockers)
Who cannot join
- Subjects prescribed metformin or have taken metformin within 1 year.
- Subjects with abnormal estimated glomerular filtration rate (eGFR).
- Hypertriglyceridemic (>400 mg/dl) and hypercholesterolemic (>260 mg/dl) subjects
- Hypertensive (>160/100 mmHg)
- Subjects with a history of significant metabolic, cardiac, congestive heart failure, cerebrovascular, hematological, pulmonary, gastrointestinal, liver, renal, or endocrine disease or cancer that in the investigator's opinion would interfere with or alter the outcome measures, or impact subject safety.
- Pregnant (as evidenced by positive pregnancy test) or nursing women
Show all 10Show fewer
- Subjects with contraindications to participation in an exercise training program
- Currently taking active weight suppression medication (e.g. phentermine,orlistat, lorcaserin, naltrexone-bupropion in combination, liraglutide, benzphetamine, diethylpropion, phendimetrazine)
- Known hypersensitivity to perflutren (contained in Definity)
- Subjects who are considered non-English speaking individuals
Trial locations and contacts
1 site in 1 country.
United States1 site
Rutgers University Loree Gymnasium
New Brunswick, New Jersey, 08901
About this study
Official title: Exercise Dose and Metformin for Vascular Health in Adults With Metabolic Syndrome
Health organizations recommend exercise in an intensity based manner to promote cardiovascular adaptation and prevent disease. Metformin is a common anti-diabetes medication that reduces future type 2 diabetes and cardiovascular disease (CVD) risk. However, the optimal dose of exercise to be combined with metformin for vascular health remains unknown. The purpose of this study is to evaluate whether combining high or low intensity exercise with metformin has the potential to outperform either exercise intensity alone on blood flow across the arterial tree as well as impact insulin action in individuals with metabolic syndrome. Identification of such outcomes will indicate 1) whether and how metformin should be combined with physical activity for CVD prevention, 2) provide the first indication of whether exercise intensity reduces CVD risk via multi-level vasculature function vs. metabolic insulin action, and 3) provide a rational early treatment for people with metabolic syndrome to prevent/treat type 2 diabetes and CVD.
- Conditions
- Metabolic Syndrome
- Being tested
- Metformin, Placebo, Low Intensity Exercise, High Intensity Exercise
- Medical subject headings
- Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Oral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d.
PlaceboDrug
Oral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets.
Low Intensity ExerciseBehavioural
Also called LoEx
Low intensity exercise will consist of 16 weeks of walking at ~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
High Intensity ExerciseBehavioural
Also called HiEx
High intensity exercise will consist of 16 weeks of walking at ~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions.
| Study group | Role | What they receive |
|---|---|---|
| LoEx with Placebo | Placebo comparator | Low intensity exercise with placebo. Receives: Drug: Placebo; Behavioral: Low Intensity Exercise |
| HiEx with Placebo | Placebo comparator | High intensity exercise with placebo. Receives: Drug: Placebo; Behavioral: High Intensity Exercise |
| LoEx with Metformin | Active comparator | Low intensity exercise with metformin. Receives: Drug: Metformin; Behavioral: Low Intensity Exercise |
| HiEx with Metformin | Active comparator | High intensity exercise with metformin. Receives: Drug: Metformin; Behavioral: High Intensity Exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Fasting Unscaled Flow Mediated Dilation (FMD) of the Brachial Artery
Endothelial function assessed as a percentage change in brachial artery diameter from baseline to deflation (5 minutes after artery occlusion by blood pressure cuff inflation). Delta = Week 16 - Week 0. Higher values and positive change scores following the intervention indicate a better outcome.
Measured: 0 and 16 weeks
Secondary outcomes (5)
Change in Metabolic Insulin Sensitivity. Glucose Infusion Rate Normalized to Steady-State Insulin (GIR).
The glucose infusion rate (mg/kg/min) divided by steady-state insulin (uU/mL) during a 120 minute euglycemic-hyperinsulinemic clamp provides an index of metabolic insulin sensitivity. Delta = Week 16 - Week 0. Higher values and positive change scores following the intervention indicate a better outcome.
Measured: 0 and 16 weeks
Change in Fasting Augmentation Index
Measure of Arterial Stiffness calculated by dividing the augmentation pressure by the pulse pressure, then multiplying by 100 and normalizing to a heart rate of 75 bpm (AIx75). Delta = Week 16 - Week 0. Lower values and negative change scores following the intervention indicate a better outcome.
Measured: 0 and 16 weeks
Change in Insulin-stimulated Microvascular Blood Flow (MBF) of the Forearm.
Product of microvascular blood volume (VI; video intensity units) and microvascular flow velocity (sec^-1). Insulin-stimulated microvascular blood flow is the change during a 120 minute euglycemic-hyperinsulinemic clamp (120-0 minutes). Delta = Week 16 - Week 0. Higher values and positive change scores following the intervention indicate a better outcome.
Measured: 0 and 16 weeks
Change in Insulin-stimulated Microvascular Flow Velocity (MFV) of the Forearm.
Replenishment curves of the forearm flexor muscle acquired during steady-state infusion of Definity microbubbles. Insulin-stimulated microvascular flow velocity is the change during a 120 minute euglycemic-hyperinsulinemic clamp (120-0 minutes). Delta = Week 16 - Week 0. Higher values and positive change scores following the intervention indicate a better outcome.
Measured: 0 and 16 weeks
Change in Insulin-stimulated Microvascular Blood Volume (MBV) of the Forearm.
Replenishment curves of the forearm flexor muscle acquired during steady-state infusion of Definity microbubbles. Insulin-stimulated microvascular blood volume is the change during a 120 minute euglycemic-hyperinsulinemic clamp (120-0 minutes). Delta = Week 16 - Week 0. Higher values and positive change scores following the intervention indicate a better outcome.
Measured: 0 and 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2017
- Study start7 Aug 2017
- Primary completion11 Mar 2024
- Study completion23 May 2024
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 (35)Papers the sponsor has linked to this study.
- Other trials for Metabolic SyndromeStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Each subject will be randomly assigned to receive low intensity exercise training + placebo, high intensity exercise training + placebo, or these exercise programs with metformin.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rutgers University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Steven K Malin, PhD, Rutgers University
- Investigators
- Steven K Malin, PhD, Principal investigator, Rutgers University - New Brunswick
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03355469
- Sponsor's protocol ID
- 19364
- Other IDs
- 1R01HL130296-01A1
- Status last verified
- Sep 2025
- First submitted
- 7 Nov 2017
- Last updated
- 22 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Laurent S, Katsahian S, Fassot C, Tropeano AI, Gautier I, Laloux B, Boutouyrie P. Aortic stiffness is an independent predictor of fatal stroke in essential hypertension. Stroke. 2003 May;34(5):1203-6. doi: 10.1161/01.STR.0000065428.03209.64. Epub 2003 Apr 3.
PubMed 12677025Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Fernando Costa. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement: Executive Summary. Crit Pathw Cardiol. 2005 Dec;4(4):198-203. doi: 10.1097/00132577-200512000-00018. No abstract available.
PubMed 18340209DeFronzo RA, Abdul-Ghani M. Assessment and treatment of cardiovascular risk in prediabetes: impaired glucose tolerance and impaired fasting glucose. Am J Cardiol. 2011 Aug 2;108(3 Suppl):3B-24B. doi: 10.1016/j.amjcard.2011.03.013.
PubMed 21802577Bateman LA, Slentz CA, Willis LH, Shields AT, Piner LW, Bales CW, Houmard JA, Kraus WE. Comparison of aerobic versus resistance exercise training effects on metabolic syndrome (from the Studies of a Targeted Risk Reduction Intervention Through Defined Exercise - STRRIDE-AT/RT). Am J Cardiol. 2011 Sep 15;108(6):838-44. doi: 10.1016/j.amjcard.2011.04.037. Epub 2011 Jul 7.
PubMed 21741606Malin SK, Nightingale J, Choi SE, Chipkin SR, Braun B. Metformin modifies the exercise training effects on risk factors for cardiovascular disease in impaired glucose tolerant adults. Obesity (Silver Spring). 2013 Jan;21(1):93-100. doi: 10.1002/oby.20235.
PubMed 23505172Malin SK, Niemi N, Solomon TP, Haus JM, Kelly KR, Filion J, Rocco M, Kashyap SR, Barkoukis H, Kirwan JP. Exercise training with weight loss and either a high- or low-glycemic index diet reduces metabolic syndrome severity in older adults. Ann Nutr Metab. 2012;61(2):135-41. doi: 10.1159/000342084.
PubMed 23036993Potteiger JA, Claytor RP, Hulver MW, Hughes MR, Carper MJ, Richmond S, Thyfault JP. Resistance exercise and aerobic exercise when paired with dietary energy restriction both reduce the clinical components of metabolic syndrome in previously physically inactive males. Eur J Appl Physiol. 2012 Jun;112(6):2035-44. doi: 10.1007/s00421-011-2174-y. Epub 2011 Sep 23.
PubMed 21947428Mestek ML, Westby CM, Van Guilder GP, Greiner JJ, Stauffer BL, DeSouza CA. Regular aerobic exercise, without weight loss, improves endothelium-dependent vasodilation in overweight and obese adults. Obesity (Silver Spring). 2010 Aug;18(8):1667-9. doi: 10.1038/oby.2009.467. Epub 2010 Jan 7.
PubMed 20057377Phillips SA, Mahmoud AM, Brown MD, Haus JM. Exercise interventions and peripheral arterial function: implications for cardio-metabolic disease. Prog Cardiovasc Dis. 2015 Mar-Apr;57(5):521-34. doi: 10.1016/j.pcad.2014.12.005. Epub 2014 Dec 18.
PubMed 25529367Tjonna AE, Lee SJ, Rognmo O, Stolen TO, Bye A, Haram PM, Loennechen JP, Al-Share QY, Skogvoll E, Slordahl SA, Kemi OJ, Najjar SM, Wisloff U. Aerobic interval training versus continuous moderate exercise as a treatment for the metabolic syndrome: a pilot study. Circulation. 2008 Jul 22;118(4):346-54. doi: 10.1161/CIRCULATIONAHA.108.772822. Epub 2008 Jul 7.
PubMed 18606913Malin SK, Gerber R, Chipkin SR, Braun B. Independent and combined effects of exercise training and metformin on insulin sensitivity in individuals with prediabetes. Diabetes Care. 2012 Jan;35(1):131-6. doi: 10.2337/dc11-0925. Epub 2011 Oct 31.
PubMed 22040838Gokce N, Keaney JF Jr, Hunter LM, Watkins MT, Nedeljkovic ZS, Menzoian JO, Vita JA. Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease. J Am Coll Cardiol. 2003 May 21;41(10):1769-75. doi: 10.1016/s0735-1097(03)00333-4.
PubMed 12767663Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol. 2010 Mar 30;55(13):1318-27. doi: 10.1016/j.jacc.2009.10.061.
PubMed 20338492Eggleston EM, Jahn LA, Barrett EJ. Early microvascular recruitment modulates subsequent insulin-mediated skeletal muscle glucose metabolism during lipid infusion. Diabetes Care. 2013 Jan;36(1):104-10. doi: 10.2337/dc11-2399. Epub 2012 Sep 6.
PubMed 22961574Liu 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 19567533
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exercise Dose and Metformin for Vascular Health in Adults With Metabolic Syndrome
- ClinicalTrials.gov ID
- NCT03355469
- Acronym / sponsor ID
- 19364
- Conditions
- Metabolic Syndrome
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 91 participants (actual)
- Lead sponsor
- Rutgers UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 7 Aug 2017 (actual)
- Primary completion
- 11 Mar 2024 (actual)
- Study completion
- 23 May 2024 (actual)
- First posted
- 28 Nov 2017 (actual)
- Results
- Posted 22 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Health organizations recommend exercise in an intensity based manner to promote cardiovascular adaptation and prevent disease. Metformin is a common anti-diabetes medication that reduces future type 2 diabetes and cardiovascular disease (CVD) risk. However, the optimal dose of exercise to be combined with metformin for vascular health remains unknown. The purpose of this study is to evaluate whether combining high or low intensity exercise with metformin has the potential to outperform either exercise intensity alone on blood flow across the arterial tree as well as impact insulin action in individuals with metabolic syndrome. Identification of such outcomes will indicate 1) whether and how metformin should be combined with physical activity for CVD prevention, 2) provide the first indication of whether exercise intensity reduces CVD risk via multi-level vasculature function vs. metabolic insulin action, and 3) provide a rational early treatment for people with metabolic syndrome to prevent/treat type 2 diabetes and CVD.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Each subject will be randomly assigned to receive low intensity exercise training + placebo, high intensity exercise training + placebo, or these exercise programs with metformin.
| Arm | Type | Receives |
|---|---|---|
| LoEx with Placebo | Placebo comparator | Drug: Placebo, Behavioral: Low Intensity ExerciseLow intensity exercise with placebo. |
| HiEx with Placebo | Placebo comparator | Drug: Placebo, Behavioral: High Intensity ExerciseHigh intensity exercise with placebo. |
| LoEx with Metformin | Active comparator | Drug: Metformin, Behavioral: Low Intensity ExerciseLow intensity exercise with metformin. |
| HiEx with Metformin | Active comparator | Drug: Metformin, Behavioral: High Intensity ExerciseHigh intensity exercise with metformin. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Male or female ≥40 and ≤80 years old.
- Has a body mass index ≥25 and ≤47 kg/m2.
- Not diagnosed with Type 2 or Type 1 diabetes
- Not currently engaged in > 150 min/wk of exercise
- Weight stable (<2kg weight change in past 3 months)
Key exclusion criteria (10 listed)
- Subjects prescribed metformin or have taken metformin within 1 year.
- Subjects with abnormal estimated glomerular filtration rate (eGFR).
- Hypertriglyceridemic (>400 mg/dl) and hypercholesterolemic (>260 mg/dl) subjects
- Hypertensive (>160/100 mmHg)
- Subjects with a history of significant metabolic, cardiac, congestive heart failure, cerebrovascular, hematological, pulmonary, gastrointestinal, liver, renal, or endocrine disease or cancer that in the investigator's opinion would interfere with or alter the outcome measures, or impact subject safety.
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 |
|---|---|---|
| MetforminOral metformin 2000 mg/d for 16 weeks. Metformin dosage will follow 500 mg/d ramp up progression: Week 1 = 500 mg/d; Week 2 = 1,000 mg/d; Week 3 = 1500 mg/d; Week 4-16 = 2000 mg/d. | Drug | HiEx with Metformin, LoEx with Metformin |
| PlaceboOral placebo for 16 weeks. Placebo tablets will follow a four-stage progression: Week 1 = 1 tablet; Week 2 = 2 tablets; Week 3 = 3 tablets; Week 4-16 = 4 tablets. | Drug | HiEx with Placebo, LoEx with Placebo |
| Low Intensity ExerciseAlso: LoExLow intensity exercise will consist of 16 weeks of walking at ~55% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions. | Behavioural | LoEx with Metformin, LoEx with Placebo |
| High Intensity ExerciseAlso: HiExHigh intensity exercise will consist of 16 weeks of walking at ~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk and the duration will be determined based on individual fitness levels to expand 400 kcals. Supervised exercise training will follow a three-phase progression: Weeks 1-2 = 3 supervised sessions at 75% duration; Week 3-4 = 3 supervised sessions at 87% duration; Weeks 5-16 = 3 supervised sessions at 100% duration. Unsupervised exercised will be 2d/wk and the duration will half the time of the supervised training sessions. | Behavioural | HiEx with Metformin, HiEx with Placebo |
Primary outcome
Change in Fasting Unscaled Flow Mediated Dilation (FMD) of the Brachial Artery
Time frame: 0 and 16 weeks
Endothelial function assessed as a percentage change in brachial artery diameter from baseline to deflation (5 minutes after artery occlusion by blood pressure cuff inflation). Delta = Week 16 - Week 0. Higher values and positive change scores following the intervention indicate a better outcome.
5 secondary outcomes
Change in Metabolic Insulin Sensitivity. Glucose Infusion Rate Normalized to Steady-State Insulin (GIR).
Time frame: 0 and 16 weeks
Change in Fasting Augmentation Index
Time frame: 0 and 16 weeks
Change in Insulin-stimulated Microvascular Blood Flow (MBF) of the Forearm.
Time frame: 0 and 16 weeks
Change in Insulin-stimulated Microvascular Flow Velocity (MFV) of the Forearm.
Time frame: 0 and 16 weeks
Change in Insulin-stimulated Microvascular Blood Volume (MBV) of the Forearm.
Time frame: 0 and 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12677025Laurent S, Katsahian S, Fassot C, Tropeano AI, Gautier I, Laloux B, Boutouyrie P. Aortic stiffness is an independent predictor of fatal stroke in essential hypertension. Stroke. 2003 May;34(5):1203-6. doi: 10.1161/01.STR.0000065428.03209.64. Epub 2003 Apr 3.
- Background: PubMed 18340209Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Fernando Costa. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement: Executive Summary. Crit Pathw Cardiol. 2005 Dec;4(4):198-203. doi: 10.1097/00132577-200512000-00018. No abstract available.
- Background: PubMed 21802577DeFronzo RA, Abdul-Ghani M. Assessment and treatment of cardiovascular risk in prediabetes: impaired glucose tolerance and impaired fasting glucose. Am J Cardiol. 2011 Aug 2;108(3 Suppl):3B-24B. doi: 10.1016/j.amjcard.2011.03.013.
- Background: PubMed 21741606Bateman LA, Slentz CA, Willis LH, Shields AT, Piner LW, Bales CW, Houmard JA, Kraus WE. Comparison of aerobic versus resistance exercise training effects on metabolic syndrome (from the Studies of a Targeted Risk Reduction Intervention Through Defined Exercise - STRRIDE-AT/RT). Am J Cardiol. 2011 Sep 15;108(6):838-44. doi: 10.1016/j.amjcard.2011.04.037. Epub 2011 Jul 7.
- Background: PubMed 23505172Malin SK, Nightingale J, Choi SE, Chipkin SR, Braun B. Metformin modifies the exercise training effects on risk factors for cardiovascular disease in impaired glucose tolerant adults. Obesity (Silver Spring). 2013 Jan;21(1):93-100. doi: 10.1002/oby.20235.
- Background: PubMed 23036993Malin SK, Niemi N, Solomon TP, Haus JM, Kelly KR, Filion J, Rocco M, Kashyap SR, Barkoukis H, Kirwan JP. Exercise training with weight loss and either a high- or low-glycemic index diet reduces metabolic syndrome severity in older adults. Ann Nutr Metab. 2012;61(2):135-41. doi: 10.1159/000342084.
- Background: PubMed 21947428Potteiger JA, Claytor RP, Hulver MW, Hughes MR, Carper MJ, Richmond S, Thyfault JP. Resistance exercise and aerobic exercise when paired with dietary energy restriction both reduce the clinical components of metabolic syndrome in previously physically inactive males. Eur J Appl Physiol. 2012 Jun;112(6):2035-44. doi: 10.1007/s00421-011-2174-y. Epub 2011 Sep 23.
- Background: PubMed 20057377Mestek ML, Westby CM, Van Guilder GP, Greiner JJ, Stauffer BL, DeSouza CA. Regular aerobic exercise, without weight loss, improves endothelium-dependent vasodilation in overweight and obese adults. Obesity (Silver Spring). 2010 Aug;18(8):1667-9. doi: 10.1038/oby.2009.467. Epub 2010 Jan 7.
- Background: PubMed 25529367Phillips SA, Mahmoud AM, Brown MD, Haus JM. Exercise interventions and peripheral arterial function: implications for cardio-metabolic disease. Prog Cardiovasc Dis. 2015 Mar-Apr;57(5):521-34. doi: 10.1016/j.pcad.2014.12.005. Epub 2014 Dec 18.
- Background: PubMed 18606913Tjonna AE, Lee SJ, Rognmo O, Stolen TO, Bye A, Haram PM, Loennechen JP, Al-Share QY, Skogvoll E, Slordahl SA, Kemi OJ, Najjar SM, Wisloff U. Aerobic interval training versus continuous moderate exercise as a treatment for the metabolic syndrome: a pilot study. Circulation. 2008 Jul 22;118(4):346-54. doi: 10.1161/CIRCULATIONAHA.108.772822. Epub 2008 Jul 7.
- Background: PubMed 22040838Malin SK, Gerber R, Chipkin SR, Braun B. Independent and combined effects of exercise training and metformin on insulin sensitivity in individuals with prediabetes. Diabetes Care. 2012 Jan;35(1):131-6. doi: 10.2337/dc11-0925. Epub 2011 Oct 31.
- Background: PubMed 12767663Gokce N, Keaney JF Jr, Hunter LM, Watkins MT, Nedeljkovic ZS, Menzoian JO, Vita JA. Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease. J Am Coll Cardiol. 2003 May 21;41(10):1769-75. doi: 10.1016/s0735-1097(03)00333-4.
- Individual participant dataSharing planned: No
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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.
Steven K Malin, PhD principal investigator
Rutgers University - New Brunswick
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Metformin, Low Intensity Exercise and High Intensity Exercise in people with Metabolic Syndrome, run by Rutgers University 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 22 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 22 Sep 2025. 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Sep 2025). 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?
Change in Fasting Unscaled Flow Mediated Dilation (FMD) of the Brachial Artery (time frame: 0 and 16 weeks). 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 NCT03355469, which also lists 35 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 22 Sep 2025.