Clinical trial NCT01545830: Metabolic Syndrome and Insulin Resistance at Allina
Official title: Randomized, Controlled Trial of Vitamin D Replenishment in Metabolic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metabolic Syndrome
Keywords: Metabolic syndrome
Insulin resistance
Vitamin D deficiency
Lead sponsor: Allina Health System
Sponsor class: OTHER
First posted: 2012-03-07
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

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:

1. reduce multiple serum cardiometabolic risk factors for both diabetes and cardiovascular disease,
2. stabilize or reverse the stage of pre-diabetes,
3. improve quality of life, and,
4. 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.

Eligibility criteria: Please Note: All participants must be an employee of Allina Health or the spouse of an Allina employee.

Inclusion Criteria:

* 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)
* 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)

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: insulin resistance score by NMR lipid fractionation
timeFrame: 6 months
measure: Reynolds Risk Score
timeFrame: 6 months
measure: Pre-diabetes stage
timeFrame: 6 months
Secondary outcomes:
measure: 25-OH-vitamin D
timeFrame: 6 months
measure: fasting lipid profile
timeFrame: 6 months
measure: adiposity markers
timeFrame: 6 months
measure: TNF-alpha
timeFrame: 6 months
measure: weight
timeFrame: 6 months
measure: blood pressure
timeFrame: 6 months
measure: PROMIS-29
timeFrame: 6 months
measure: Perceived Stress Scale (PSS)
timeFrame: 6 months
measure: WPAI
timeFrame: 6 months
measure: PROMIS-GH
timeFrame: 6 months
measure: International Physical Activity Questionnaire (IPAQ)
timeFrame: 6 months
measure: IL-6
timeFrame: 6 months
measure: IL-8
timeFrame: 6 months
measure: HS-CRP
timeFrame: 6 months
measure: Lp-PLA2 (PLAC)
timeFrame: 6 months
measure: PAI-1
timeFrame: 6 months
measure: Fibrinogen
timeFrame: 6 months
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Allina Health
state: Minnesota
Study officials:
affiliation: Allina Health
name: Gregory Plotnikoff, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Allina Health
name: Jeffery Dusek, PhD
role: STUDY_DIRECTOR
affiliation: Allina Health
name: Shaina Biron
role: STUDY_DIRECTOR
References: