Effect of Vitamin D Repletion on Insulin Resistance and Systemic Inflammation

• ClinicalTrials.gov Identifier: NCT01354964
• Recruitment Status: Completed
• First Posted: May 17, 2011
• Results First Posted: March 9, 2020
• Last Update Posted: November 2, 2020
• Sponsor: Albert Einstein College of Medicine
• Collaborator: National Center for Research Resources (NCRR)
• Information provided by (Responsible Party): Meredith Hawkins, Albert Einstein College of Medicine

Study Description

Brief Summary:

The purpose of this research is to study the effects of Vitamin D supplementation on the body's response to insulin (a hormone that controls blood sugar), on inflammation, and on specific cells and processes in fat tissue.

Condition or disease	Intervention/treatment	Phase
Insulin Resistance	Drug: Vitamin D; Drug: Placebo	Phase 2

Detailed Description:

Over the last several years, studies have shown that low vitamin D levels may increase risk of developing Type 2 Diabetes. The investigators will administer vitamin D3 (cholecalciferol) to non-diabetic, insulin resistant subjects with vitamin D deficiency (total vitamin D levels <20 ng/ml) to increase the level of vitamin D3. The investigators will study the effects of increased Vitamin D on insulin action, adipose tissue inflammation, and on certain cells and processes in fat tissue.

Investigators will study participants with a procedure called a "pancreatic clamp" study. During the clamp procedure, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of glucose in the blood) are infused with an intravenous catheter, and blood samples are collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are found in the body and are related to glucose metabolism. Adipose tissue inflammation will be measured using the following inflammatory markers: IL-6, PAI-1, TNF-alpha, and iNOS.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of Vitamin D Repletion on Insulin Resistance and Systemic Inflammation
• Actual Study Start Date: March 13, 2009
• Actual Primary Completion Date: June 3, 2015
• Actual Study Completion Date: September 3, 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Vitamin D; Participants received weekly oral vitamin D drops using a weight-based calculated dosage for up to six months.	Drug: Vitamin D; Other Name: Vitamin D3 (cholecalciferol)
Placebo Comparator: Placebo; Participants received weekly oral placebo drops (similar in taste and appearance to vitamin D) for up to six months.	Drug: Placebo

Outcome Measures

Primary Outcome Measures :

1. Percent Change in Hepatic Insulin Sensitivity [ Time Frame: 2nd clamp visit (after up to 3 months) and 3rd clamp visit (after up to 6 months) ]
   Endogenous glucose production (EGP) was assessed at each study visit to evaluate hepatic insulin sensitivity. Percent change between the EGP at baseline and second visit (after treatment for up to 3 months with Vitamin D to reach a target level of ≥30 ng/ml), and baseline and third visits (after treatment for up to 6 months with Vitamin D in order to reach a target level of ≥50 ng/ml) will be calculated.

Secondary Outcome Measures :

1. Percent Change in Peripheral Glucose Uptake [ Time Frame: 2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months) ]
   The rate of glucose uptake to determine peripheral insulin sensitivity was measured using the rate of disappearance (Rd) of glucose at each study visit. Percent change between the Rd at baseline and second visit (after treatment with Vitamin D for up to 3 months to target level of ≥30 ng/ml), and baseline and third visits (after treatment with Vitamin D for up to 6 months to target level of ≥50 ng/ml) will be calculated.
2. Evaluated Expression of Pro-inflammatory Gene TNF-α [ Time Frame: 2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months) ]
   Adipose tissue macrophages will be isolated from subcutaneous abdominal adipose tissue, and will be quantified by fluorescence activated cell sorting (FACS) analysis. TNF-α gene expression will be examined by real-time (rt-PCR) and will provide a measure of macrophage activation at baseline, at 2nd study visit (after treatment with Vitamin D to a goal level of ≥30 ng/ml), and at 3rd study visit (goal Vitamin D level of ≥50 ng/ml). The mRNA copy number is then compared with a reference gene copy number (5 commonly used house keeping genes [HKGs]) as a ratio, which is a measure of relative gene expression.
3. Evaluated Expression of Pro-inflammatory Gene IL-6 [ Time Frame: 2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months) ]
   Adipose tissue macrophages will be isolated from subcutaneous abdominal adipose tissue, and will be quantified by fluorescence activated cell sorting (FACS) analysis. IL-6 gene expression will be examined by real-time (rt-PCR) and will provide a measure of macrophage activation at baseline, at 2nd study visit (after treatment with Vitamin D to a goal level of ≥30 ng/ml), and at 3rd study visit (goal Vitamin D level of ≥50 ng/ml). The mRNA copy number is then compared with a reference gene copy number (5 commonly used house keeping genes [HKGs]) as a ratio, which is a measure of relative gene expression.
4. Evaluated Expression of Pro-inflammatory Gene iNOS [ Time Frame: 2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months) ]
   Adipose tissue macrophages will be isolated from subcutaneous abdominal adipose tissue, and will be quantified by fluorescence activated cell sorting (FACS) analysis. iNOS gene expression will be examined by real-time (rt-PCR) and will provide a measure of macrophage activation at baseline, at 2nd study visit (after treatment with Vitamin D to a goal level of ≥30 ng/ml), and at 3rd study visit (goal Vitamin D level of ≥50 ng/ml). The mRNA copy number is then compared with a reference gene copy number (5 commonly used house keeping genes [HKGs]) as a ratio, which is a measure of relative gene expression.
5. Evaluated Expression of Pro-inflammatory Gene PAI-1 [ Time Frame: 2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months) ]
   Adipose tissue macrophages will be isolated from subcutaneous abdominal adipose tissue, and will be quantified by fluorescence activated cell sorting (FACS) analysis. PAI-1 gene expression will be examined by real-time (rt-PCR) and will provide a measure of macrophage activation at baseline, at 2nd study visit (after treatment with Vitamin D to a goal level of ≥30 ng/ml), and at 3rd study visit (goal Vitamin D level of ≥50 ng/ml). The mRNA copy number is then compared with a reference gene copy number (5 commonly used house keeping genes [HKGs]) as a ratio, which is a measure of relative gene expression.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Serum 25(OH)D<20ng/ml
• Insulin Resistant based on HOMA-IR score of >3
• Able and willing to provide informed consent
• BMI 20-35

Exclusion Criteria:

• HIV/AIDS
• History of any cancer
• Sarcoidosis
• Alcohol or substance abuse
• Cushing's syndrome
• Primary hyperparathyroidism
• Nephrolithiasis
• Pregnancy or breastfeeding
• Regular visits to a tanning salon
• Hypercalcemia or hypocalcemia
• Untreated or uncontrolled hypertension
• Any chronic illness requiring medication, other than arthritis, hypertension and hyperlipidemia

Contacts and Locations

Locations

United States, New York

Albert Einstein College of Medicine

Bronx, New York, United States, 10461

Sponsors and Collaborators

Albert Einstein College of Medicine

National Center for Research Resources (NCRR)

Investigators

• Principal Investigator: Meredith A Hawkins, M.D., M.S.; Albert Einstein College of Medicine

More Information

• Responsible Party: Meredith Hawkins, Professor of Medicine (Endocrinology), Albert Einstein College of Medicine
• ClinicalTrials.gov Identifier: NCT01354964
• Other Study ID Numbers: 2008-225; 5K23RR023335-02 ( U.S. NIH Grant/Contract )
• First Posted: May 17, 2011
• Results First Posted: March 9, 2020
• Last Update Posted: November 2, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Meredith Hawkins, Albert Einstein College of Medicine:

Glucose Metabolism Disorders; Insulin Resistance; Endocrine System; Vitamin D

Additional relevant MeSH terms:

Insulin Resistance; Inflammation; Pathologic Processes; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents