Metabolic SyndromePhase 2MISURANCT01545830
Metabolic Syndrome and Insulin Resistance at Allina
A Phase 2 study testing vitamin D3 (cholecalciferol) in people with Metabolic Syndrome, run by Allina Health System at 1 site in United States.
Trial summary
Vitamin D deficiency is widespread and appears to represent one easily and inexpensively modifiable risk factor for diabetes and cardiovascular disease. More than 40 years of data link hypovitaminosis D to metabolic syndrome, insulin resistance, hyperglycemia, type 2 diabetes and increased cardiovascular risk. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Metabolic Syndrome
- What is being tested?
- vitamin D3 (cholecalciferol)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2012to Mar 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Vitamin D deficiency, defined as 25-OH vitamin D ≤ 25 ng/ml
- Metabolic syndrome as defined by more than three or more of the following:
- Elevated waist circumference
- Men - Equal to or greater than 40 inches
- Women - Equal to or greater than 35 inches
- Elevated serum triglycerides (≥150 mg/dL)
Show all 10Show fewer
- Men - Less than 40 mg/dL
- Women - Less than 50 mg/dL
- Elevated blood pressure (≥130/85 or use of medication for hypertension)
- Elevated fasting glucose (≥100 mg/dL or use of medication for hyperglycemia)
Who cannot join
- Known cardiovascular disease defined as current or prior coronary heart disease, stroke/transient ischemic attack, heart failure, or peripheral vascular disease.
- During the study, addition of any medications known to change outcome measures including medications or supplements for hyperlipidemia, hypertension, weight loss, diabetes.
- Current Vitamin D supplementation beyond that found in a multivitamin (400 IU)
- Current calcium supplementation greater than 600 mg
- Untreated blood pressure greater than 159/99 at baseline
- Treated blood pressure greater than 150/90 at baseline
Show all 9Show fewer
- Any condition which could limit the ability to complete and comply with 6-month study
- Unwillingness or inability to comply with study requirements
- Known allergy to coconut or coconut oil
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized, Controlled Trial of Vitamin D Replenishment in Metabolic Syndrome
Vitamin D deficiency is widespread and appears to represent one easily and inexpensively modifiable risk factor for diabetes and cardiovascular disease. More than 40 years of data link hypovitaminosis D to metabolic syndrome, insulin resistance, hyperglycemia, type 2 diabetes and increased cardiovascular risk.
Screening for vitamin D deficiency followed by supplementation in appropriate individuals could be among the simplest and most cost-effective measures for reducing metabolic syndrome and insulin resistance in the general population.
Read more
This study will test the hypothesis that increasing vitamin D status in vitamin D deficient individuals with metabolic syndrome will:
- reduce multiple serum cardiometabolic risk factors for both diabetes and cardiovascular disease,
- stabilize or reverse the stage of pre-diabetes,
- improve quality of life, and,
- improve the ability to make health-related behavioral changes.
Read the detailed description
Longitudinal observational studies suggest a significant inverse association between vitamin D status and both incident and prevalent metabolic syndrome/type II diabetes. Results from small underpowered trials and post-hoc analyses of data from larger trials designed for bone-specific outcomes suggest that vitamin D may slow the progression to diabetes in adults with glucose intolerance. However, at this time, no randomized trials of sufficient size exist to assess effectiveness.
Importantly, in the investigators' own study of over 10,000 Allina employees, the investigators found that 6% of these employees had levels less than 10 ng/mL, 30% less than 20 ng/ml and 60% less than 30 ng/ml. Recently, the Intermountain Heart Collaborative Study Group reviewed 41,504 patient records with at least one measured vitamin D level. Surprisingly, both the Intermountain and the Allina Employee study demonstrate vitamin D deficiency (≤30 ng/ml) in more than 60% of people tested with only minor differences by gender or age (Plotnikoff GA, Finch M, Dusek JA. Impact of Vitamin D Deficiency on the Productivity of a Health Care Workforce. J Occup Environ Med (in press)).
Furthermore, the Intermountain group demonstrated that vitamin D levels less than 30 ng/ml, compared to levels greater than 30 ng/ml, were associated with highly significant (p <0.0001) increases in the prevalence of diabetes, hypertension, hyperlipidemia, and peripheral vascular disease. Also, those without risk factors but with severe deficiency had an increased likelihood of developing diabetes, hypertension, and hyperlipidemia. The vitamin D levels were also highly associated with coronary artery disease, myocardial infarction, heart failure, and stroke (all p <0.0001), as well as with incident death, heart failure, coronary artery disease/myocardial infarction (all p <0.0001), stroke (p = 0.003), and their composite (p <0.0001).
Numerous prevention efforts are underway to minimize the predicted economic and human burdens from these increasingly common diseases. However, few, if any, prospective clinical trials are underway with vitamin D interventions. This trial is specifically designed to prospectively test the impact of vitamin D replenishment on both metabolic syndrome and insulin resistance.
The 2011 Endocrine Society guidelines assert that vitamin D intakes above the current recommendations may be associated with better health outcomes. However, there is no consensus on the optimal 25(OH)D concentration necessary to minimize metabolic syndrome, insulin resistance and progression to diabetes. This trial is designed to prospectively identify optimal serum levels for reduction of cardiometabolic risk factors.
- Conditions
- Metabolic Syndrome
- Being tested
- vitamin D3 (cholecalciferol)
- Keywords
- Metabolic syndrome, Insulin resistance, Vitamin D deficiency
- Medical subject headings
- Metabolic Syndrome, Insulin Resistance, Vitamin D Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vitamin D3 (cholecalciferol)Dietary supplement
Also called D-Drops
Active intervention: 6,000 IUs taken by mouth daily for 6 months Active Comparator: 600 IUs taken by mouth daily for 6 months
| Study group | Role | What they receive |
|---|---|---|
| Regular Dose | Active comparator | Intervention: 600 IUs of cholecalciferol taken by mouth daily. Receives: Dietary Supplement: vitamin D3 (cholecalciferol) |
| High Dose D | Experimental | Intervention: 6,000 IUs of cholecalciferol taken by mouth daily. Receives: Dietary Supplement: vitamin D3 (cholecalciferol) |
What is being measured
The primary outcome is the main question the study is designed to answer.
insulin resistance score by NMR lipid fractionation
additional insulin resistance measure
Measured: 6 months
Reynolds Risk Score
The Reynolds Risk Score is designed to predict one's risk of having a future heart attack, stroke, or other major heart disease in the next 10 years. In addition to your age, blood pressure, cholesterol levels and whether you currently smoke, the Reynolds Risk Score uses information from two other risk factors, a blood test called hsCRP (a measure of inflammation) and whether or not either of your parents had a heart attack before they reached age 60 (a measure of genetic risk).
Measured: 6 months
Pre-diabetes stage
The pre-diabetes stage, a marker of progression toward type 2 diabetes mellitus, is a calculated score based upon results of fasting adiponectin, insulin and proinsulin.
Measured: 6 months
Secondary outcomes (17)
25-OH-vitamin D
25-OH-vitamin D is the best measure of vitamin D status.
Measured: 6 months
fasting lipid profile
Measured: 6 months
adiposity markers
Adiponectin: This adipocyte-derived protein increases hepatic and peripheral insulin sensitivity, moderates fat tissue growth, decreases lipid and glucose production in the liver and suppresses vascular inflammation. This measure declines as insulin resistance increases.
Leptin: This adipocyte-derived hormone plays a key role in regulating neuroendocrine and immune function, appetite, metabolic rate and body weight. Many overweight individuals have elevated levels and leptin resistance.
Measured: 6 months
TNF-alpha
Inflammatory markers: TNF-alpha, IL-6, IL-8. These inflammatory mediators are central to the pathophysiology of obesity and its systemic effects
Measured: 6 months
weight
Measured: 6 months
blood pressure
Measured: 6 months
PROMIS-29
PROMIS is a questionnaire data bank developed and made available by the National Institutes of Health for research purposes. It is used to measure the core domains of physical functioning, fatigue, pain, depression, anxiety, and social role participation.
Measured: 6 months
Perceived Stress Scale (PSS)
The PSS is brief, validated and widely used psychological instrument for assessing a participant's perception of stress. The PSS-4 consists of 4 questions to measure the degree to which situations in the participant's life are perceived as stressful including questions related to perceived unpredictability and lack of control.
Measured: 6 months
WPAI
This 6 item, validated instrument measures work and general activity impairment due to health problems. It uses a seven day recall and has been adapted for use in populations with differing health problems.
Measured: 6 months
PROMIS-GH
PROMIS is a questionnaire data bank developed and made available by the National Institutes of Health for research purposes. The PROMIS-GH consists of 10 items, representing multiple domains and can be scored into a Global Physical Health component and a Global Mental Health component
Measured: 6 months
International Physical Activity Questionnaire (IPAQ)
The International Physical Activity Questionnaire (IPAQ) short form (4 generic items) versions for use by either telephone or self-administered methods are available. The purpose of the questionnaire is to provide a common instrument that can be used to obtain internationally comparable data on health related physical activity. The development of this international measure for physical activity commenced in Geneva in 1998 and was followed by extensive reliability and validity testing undertaken in 12 countries (14 sites) across 6 continents during 2000.
Measured: 6 months
IL-6
Inflammatory mediators, including IL-6, are central to the pathophysiology of obesity and its systemic effects.
Measured: 6 months
IL-8
Inflammatory mediators, inlcuding IL-8, are central to the pathophysiology of obesity and its systemic effects.
Measured: 6 months
HS-CRP
Elevated HS-CRP predicts the development of type II diabetes and is a crucial factor in calculating the Reynolds Risk Score.
Measured: 6 months
Lp-PLA2 (PLAC)
This is an enzyme produced by inflammatory cells that hydrolyzes oxidized phospholipids in HDL and catalyzes the degradation of PAF, platelet activating factor. Levels are positively correlated with increased risk of developing coronary artery disease and stroke.
Measured: 6 months
PAI-1
This is the primary inhibitor of plasminogen activation. Elevated levels predispose to clot formation by inhibiting fibrinolytic activity.
Measured: 6 months
Fibrinogen
Fibrinogen is also known as coagulation Factor I. Elevated levels are associated with cardiovascular disease. This is an acute-phase protein that is elevated in any form of inflammation.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2012 (estimated)
- Study startMar 2012
- Primary completionFeb 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Allina Health System
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jeffery Dusek, Allina Health System
- Investigators
- Gregory Plotnikoff, MD, Principal investigator, Allina Health SystemJeffery Dusek, PhD, Study director, Allina Health SystemShaina Biron, Study director, Allina Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01545830
- Sponsor's protocol ID
- SPA ID 3607
- Acronym
- MISURA
- Status last verified
- Aug 2016
- First submitted
- 28 Feb 2012
- Last updated
- 1 Sep 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Controlled Trial of Vitamin D Replenishment in Metabolic Syndrome
- ClinicalTrials.gov ID
- NCT01545830
- Acronym / sponsor ID
- MISURA / SPA ID 3607
- Conditions
- Metabolic Syndrome
- Keywords
- Metabolic syndrome, Insulin resistance, Vitamin D deficiency
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Allina Health SystemUniversity, hospital or other
- Study start
- Mar 2012
- Primary completion
- Feb 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 7 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Vitamin D deficiency is widespread and appears to represent one easily and inexpensively modifiable risk factor for diabetes and cardiovascular disease. More than 40 years of data link hypovitaminosis D to metabolic syndrome, insulin resistance, hyperglycemia, type 2 diabetes and increased cardiovascular risk.
Screening for vitamin D deficiency followed by supplementation in appropriate individuals could be among the simplest and most cost-effective measures for reducing metabolic syndrome and insulin resistance in the general population.
This study will test the hypothesis that increasing vitamin D status in vitamin D deficient individuals with metabolic syndrome will:
- reduce multiple serum cardiometabolic risk factors for both diabetes and cardiovascular disease,
- stabilize or reverse the stage of pre-diabetes,
- improve quality of life, and,
- improve the ability to make health-related behavioral changes.
Detailed description
Longitudinal observational studies suggest a significant inverse association between vitamin D status and both incident and prevalent metabolic syndrome/type II diabetes. Results from small underpowered trials and post-hoc analyses of data from larger trials designed for bone-specific outcomes suggest that vitamin D may slow the progression to diabetes in adults with glucose intolerance. However, at this time, no randomized trials of sufficient size exist to assess effectiveness.
Importantly, in the investigators' own study of over 10,000 Allina employees, the investigators found that 6% of these employees had levels less than 10 ng/mL, 30% less than 20 ng/ml and 60% less than 30 ng/ml. Recently, the Intermountain Heart Collaborative Study Group reviewed 41,504 patient records with at least one measured vitamin D level. Surprisingly, both the Intermountain and the Allina Employee study demonstrate vitamin D deficiency (≤30 ng/ml) in more than 60% of people tested with only minor differences by gender or age (Plotnikoff GA, Finch M, Dusek JA. Impact of Vitamin D Deficiency on the Productivity of a Health Care Workforce. J Occup Environ Med (in press)).
Furthermore, the Intermountain group demonstrated that vitamin D levels less than 30 ng/ml, compared to levels greater than 30 ng/ml, were associated with highly significant (p <0.0001) increases in the prevalence of diabetes, hypertension, hyperlipidemia, and peripheral vascular disease. Also, those without risk factors but with severe deficiency had an increased likelihood of developing diabetes, hypertension, and hyperlipidemia. The vitamin D levels were also highly associated with coronary artery disease, myocardial infarction, heart failure, and stroke (all p <0.0001), as well as with incident death, heart failure, coronary artery disease/myocardial infarction (all p <0.0001), stroke (p = 0.003), and their composite (p <0.0001).
Numerous prevention efforts are underway to minimize the predicted economic and human burdens from these increasingly common diseases. However, few, if any, prospective clinical trials are underway with vitamin D interventions. This trial is specifically designed to prospectively test the impact of vitamin D replenishment on both metabolic syndrome and insulin resistance.
The 2011 Endocrine Society guidelines assert that vitamin D intakes above the current recommendations may be associated with better health outcomes. However, there is no consensus on the optimal 25(OH)D concentration necessary to minimize metabolic syndrome, insulin resistance and progression to diabetes. This trial is designed to prospectively identify optimal serum levels for reduction of cardiometabolic risk factors.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Regular Dose | Active comparator | Dietary Supplement: vitamin D3 (cholecalciferol)Intervention: 600 IUs of cholecalciferol taken by mouth daily. |
| High Dose D | Experimental | Dietary Supplement: vitamin D3 (cholecalciferol)Intervention: 6,000 IUs of cholecalciferol taken by mouth daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Vitamin D deficiency, defined as 25-OH vitamin D ≤ 25 ng/ml
- Metabolic syndrome as defined by more than three or more of the following:
- Elevated waist circumference
- Men - Equal to or greater than 40 inches
- Women - Equal to or greater than 35 inches
Key exclusion criteria (9 listed)
- Known cardiovascular disease defined as current or prior coronary heart disease, stroke/transient ischemic attack, heart failure, or peripheral vascular disease.
- During the study, addition of any medications known to change outcome measures including medications or supplements for hyperlipidemia, hypertension, weight loss, diabetes.
- Current Vitamin D supplementation beyond that found in a multivitamin (400 IU)
- Current calcium supplementation greater than 600 mg
- Untreated blood pressure greater than 159/99 at baseline
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 |
|---|---|---|
| vitamin D3 (cholecalciferol)Also: D-DropsActive intervention: 6,000 IUs taken by mouth daily for 6 months Active Comparator: 600 IUs taken by mouth daily for 6 months | Dietary supplement | High Dose D, Regular Dose |
Primary outcome
insulin resistance score by NMR lipid fractionation
Time frame: 6 months
additional insulin resistance measure
Reynolds Risk Score
Time frame: 6 months
The Reynolds Risk Score is designed to predict one's risk of having a future heart attack, stroke, or other major heart disease in the next 10 years. In addition to your age, blood pressure, cholesterol levels and whether you currently smoke, the Reynolds Risk Score uses information from two other risk factors, a blood test called hsCRP (a measure of inflammation) and whether or not either of your parents had a heart attack before they reached age 60 (a measure of genetic risk).
Pre-diabetes stage
Time frame: 6 months
The pre-diabetes stage, a marker of progression toward type 2 diabetes mellitus, is a calculated score based upon results of fasting adiponectin, insulin and proinsulin.
17 secondary outcomes
25-OH-vitamin D
Time frame: 6 months
fasting lipid profile
Time frame: 6 months
adiposity markers
Time frame: 6 months
TNF-alpha
Time frame: 6 months
weight
Time frame: 6 months
blood pressure
Time frame: 6 months
PROMIS-29
Time frame: 6 months
Perceived Stress Scale (PSS)
Time frame: 6 months
WPAI
Time frame: 6 months
PROMIS-GH
Time frame: 6 months
International Physical Activity Questionnaire (IPAQ)
Time frame: 6 months
IL-6
Time frame: 6 months
IL-8
Time frame: 6 months
HS-CRP
Time frame: 6 months
Lp-PLA2 (PLAC)
Time frame: 6 months
PAI-1
Time frame: 6 months
Fibrinogen
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2016.
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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.
Gregory Plotnikoff, MD principal investigator
Allina Health System
Jeffery Dusek, PhD study director
Allina Health System
Shaina Biron study director
Allina Health System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing vitamin D3 (cholecalciferol) in people with Metabolic Syndrome, run by Allina Health System 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 10 inclusion and 9 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 1 Sep 2016. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
insulin resistance score by NMR lipid fractionation (time frame: 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Sep 2016.