Effect of Vitamin D Supplementation on Endothelial Function in Obese Adolescents

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Seema Kumar, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01746264
First received: November 16, 2012
Last updated: March 30, 2016
Last verified: March 2016
  Purpose
Vitamin D deficiency has been linked to endothelial dysfunction in adults. Obese adolescents have a high prevalence of Vitamin D deficiency as well as evidence of endothelial dysfunction. Our hypothesis is that supplementation of Vitamin D deficient adolescents with Vitamin D would lead to improvement in endothelial dysfunction.

Condition Intervention Phase
Obesity
Endothelial Dysfunction
Vitamin D Deficiency
Dietary Supplement: Vitamin D3
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Effect of Vitamin D Supplementation on Endothelial Function in Obese Adolescents

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Flow Mediated Dilatation (FMD) [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    Endothelial function was assessed by FMD, via a high-resolution Doppler ultrasonography examination of the right brachial artery. FMD was calculated as the maximal percentage increase in brachial artery diameter (BAD) from baseline after the release of cuff occlusion.


Secondary Outcome Measures:
  • 25-hydroxy Vitamin D (25[OH]D) Levels [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    25(OH)D was measured using liquid chromatography-tandem mass spectrometry. Total 25(OH)D concentrations of each sample was calculated using internal standard, 25(OH)D_2 and 25(OH)D_3.

  • Total Cholesterol [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    Total cholesterol levels were measured by an enzymatic colorimetric assay.

  • Triglycerides [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    Total triglyceride levels were measured by an enzymatic colorimetric assay.

  • Body Mass Index [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    Body Mass Index (BMI) is a health index for comparing weight to height. BMI is a person's weight in kilograms (kg) divided by his or her height in meters squared. The body mass index is an indication if a person is at a suitable weight for his height on an approximation of body fat. A body mass index of under 20 is considered to be underweight, while a body mass index between 20 to 25 is considered healthy. A body mass index in the range of 25 to 30 is regarded as overweight. A body mass index over 30 is regarded as obese.

  • International Physical Activity Questionnaire (IPAQ) Short Form Score [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    The IPAQ short form used asked 7 questions about activities in the last 7 days, covering vigorous physical activities, moderate activities, walking, and sitting, asking for days per week, hours per day or minutes per day. The score is reported in metabolic equivalent (MET)-minutes per week. Possible scores could range from 0 (inactive) to greater than 3000 MET-minutes/week (highly active). The definition of high activity was vigorous intensity activity on at least 3 days achieving a minimum total activity of at least 1500 MET-minutes/week OR 7 days of any combination of walking, moderate-intensity or vigorous-intensity activities achieving a minimum total physical activity of at least 3000 MET-minutes/week. Therefore a score of > 3000 MET-minutes/week was possible.

  • Calcium Intake Per Day [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    Calcium intake was measured using the validated Short Calcium Questionnaire (SCQ). This questionnaire is in the form of an spreadsheet, and asks the participant to enter the number of servings per week of various food items and vitamin or mineral supplements. The spreadsheet calculates the daily calcium intake (mg/day) from the data entered.

  • Serum Parathyroid Hormone (PTH) [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    A parathyroid hormone (PTH) blood test measures the level of parathyroid hormone in the blood. This test is used to help identify hyperparathyroidism, to find the cause of abnormal calcium levels, or to check the status of chronic kidney disease. PTH controls calcium and phosphorus levels in the blood. PTH was measured by a two-site chemiluminescent immunometric assay.

  • Fasting Glucose [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    Plasma glucose was measured by hexokinase enzymatic assay.

  • Fasting Insulin [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    Serum insulin was measured using commercial electrochemiluminescence immunoassay kits.

  • Homeostatic Model Assessment of Insulin Resistance Index (HOMA-IR) [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    This calculation measures insulin resistance, and requires U.S. standard units. The healthy range is 0.5 to 1.4. Less than 1.0 means the subject is insulin-sensitive, which is optimal. Above 1.9 indicates early insulin resistance. Above 2.9 indicates significant insulin resistance. The HOMA-IR was calculated as: HOMA-IR = fasting serum glucose (mmol/L) x fasting insulin (mU/mL)/22.5.

  • High Sensitivity C-reactive Protein (Hs-CRP) [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    A high-sensitivity C-reactive protein (hs-CRP) test may be used to help evaluate an individual for risk of cardiovascular disease (CVD). C-reactive protein (CRP) is a protein that increases in the blood with inflammation. Studies have suggested that a persistent low level of inflammation plays a major role in atherosclerosis, the narrowing of blood vessels due to build-up of cholesterol and other lipids, which is often associated with CVD. The hs-CRP test accurately measures low levels of C-reactive protein to identify low but persistent levels of inflammation and thus helps predict a person's risk of developing CVD. hs-CRP was measured using particle-enhanced immunonephelometry.

  • Low-density Lipoprotein Cholesterol (LDL) Cholesterol Levels [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    The test for low-density lipoprotein cholesterol is used as part of a lipid profile to predict an individual's risk of developing heart disease. A desirable level is <3.36 mmol/L; borderline high is 3.36 - 4.11 mmol/L; high is >/= 4.14 mmol/L. LDL cholesterol was calculated as: LDL = Total cholesterol - HDL cholesterol - Triglycerides/5.

  • High Density Lipoprotein (HDL) Cholesterol Levels [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    Total HDL cholesterol levels were measured by an enzymatic colorimetric assay. The test for high-density lipoprotein cholesterol (HDL-C) is used along with other lipid tests to screen for unhealthy levels of lipids and to determine the risk of developing heart disease. If a subject has a negative risk factor, a desirable HDL level would be >/= 1.55 mmol/L.

  • Urine Calcium to Creatinine Ratio [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    Urine calcium/creatinine ratio (unit mg/g) on random urine sample was calculated by dividing calcium in mg by creatinine in g.

  • Reactive Hyperemia Index (RHI) [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    The cuff of a sphygmomanometer was placed on the forearm and inflated to 50 mm Hg above the participant's systolic blood pressure for a period of 5 min. The increase in resting brachial blood flow was calculated as the maximum flow recorded in the first 15 seconds after cuff deflation and expressed as a percentage increase from baseline reactive. Higher values are considered normal or improved endothelial function.


Enrollment: 19
Study Start Date: November 2012
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vitamin D3
Vitamin D3 supplementation at 100,000 IU once a month for 3 months
Dietary Supplement: Vitamin D3
Vitamin D 3 at 100,000 IU once a month for 3 months
Other Name: Cholecalciferol

Detailed Description:

Subjects had a brief screening visit with one of the study team members. Past medical history, current medications and a brief dietary history was taken. The dietary history was taken to assess calcium intake in a day and was obtained via the validated Short Calcium questionnaire. Blood pressure, heart rate as well as height,weight, waist and hip circumference measurement was obtained by study staff. In addition, a brief physical examination to determine Tanner stage was also completed. This involved examination of both breasts and genitalia for adolescent female and only genitalia in males. A physical activity questionnaire (IPAQ) was also administered by the study staff at this visit. A blood draw of 5 ml to measure plasma 25(OH) D, calcium, phosphorus was obtained as part of the screening visit. For girls who had started menstruating, a urine pregnancy test was also obtained.

After the screening visit eligible subjects had baseline biochemical tests and an endothelial function assessment. Study participants received a pill container with six total pills of vitamin cholecalciferol (D3) (1 pill = 50,000 IU), with directions to take two pills once a month (100,000 IU) at the same time for a period of 3 months. Compliance was assessed at the 3 month visit by counting the number of pills remaining in the container.

At 1 month, the subjects had tests for serum calcium and 25 hydroxy vitamin D levels. A urine test for random calcium to creatinine ratio was also obtained.

At 2 months, the serum calcium, 25 hydroxy vitamin D levels, and calcium to creatinine ratio tests were repeated.

At the end of 3 months, biochemical tests and an endothelial function assessment were repeated. Medical history, questionnaires, and the physical exam were also repeated.

  Eligibility

Ages Eligible for Study:   12 Years to 18 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age 12-18 years
  2. BMI >95% for age and gender
  3. 25 (OH) D levels less than 30 ng/ml

Exclusion Criteria:

  1. 25 (OH) D levels >30 ng/mL
  2. Serum calcium >10.4 mg/dL
  3. Serum phosphorus > 4.7 mg/dl
  4. Pregnancy or nursing
  5. Current cancer
  6. Patients on vitamin D3 supplementation exceeding 400 IU/day
  7. Hypertension defined as Blood Pressure over the 95th percentile for age, gender and height
  8. Dietary calcium intake exceeding 1500 mg/day
  9. Hepatic or renal disorders
  10. Type 1 or type 2 diabetes mellitus
  11. Subjects receiving insulin, metformin, or oral hypoglycemic medications
  12. Subjects with malabsorption disorders (celiac disease, cystic fibrosis, inflammatory bowel disease)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01746264

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Seema Kumar, MD Mayo Clinic
  More Information

Publications:
Responsible Party: Seema Kumar, PI, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01746264     History of Changes
Other Study ID Numbers: 12-006349  UL1TR000135 
Study First Received: November 16, 2012
Results First Received: January 25, 2016
Last Updated: March 30, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
Obesity
Endothelial dysfunction
Vitamin D deficiency

Additional relevant MeSH terms:
Vitamin D Deficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Vitamins
Vitamin D
Ergocalciferols
Cholecalciferol
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on July 28, 2016