Correction of Vitamin D Levels and Its Effect on Insulin Resistance and Weight Gain in Obese Youth

NCT02168660 | Completed Phase 2 Results DMC

• 1 other identifier: UT092010-217
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 1

Brief Summary

Vitamin D deficiency is extremely common in obese youth. In our obese population followed in the Endocrinology clinic at Children's Medical Center Dallas, vitamin D levels were inversely correlated with a measure of insulin resistance. We propose to show that correction of vitamin D levels in obese children and adolescents improves their insulin sensitivity. Obese youth presenting to the Center for Obesity and its Consequences on Health (COACH) clinic will be randomized to receive either the most recent Institute of Medicine (IOM) recommendations of minimum D3 dose of 600 IU/day (1), or receive higher doses of D3 such that the blood levels of vitamin D will be brought to a target level in either the low part or high part of the normal range. The goal is to determine if correction of vitamin D deficiency will improve insulin sensitivity in this group. Secondary goals include determining whether correction of vitamin D deficiency in obese adolescents and children results in less weight gain, and determining the amount of D3 required to correct vitamin D levels in this population. Our specific hypotheses are as follows: Hypothesis #1 Obese youth treated with Vitamin D3 who achieve low-normal 25-hydroxyvitamin D3 (OHD) levels (30-50 ng/mL) or high-normal 25-OHD levels (60-80 ng/mL) will have improved insulin resistance, as measured by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), compared to those individuals with deficient 25-OHD levels (\< 30 ng/mL). Hypothesis #2 Subjects with a higher BMI will have higher Vitamin D dose requirements than current IOM recommendations of 600 IU/day and will take a longer period of time to reach target 25-OHD levels. Hypothesis #3 Subjects with normal 25-OHD levels will demonstrate less weight gain compared to subjects on the control arm.

Conditions

Obesity; Insulin Resistance; Vitamin D Deficiency

Keywords

Obesity; Insulin Resistance; Vitamin D Deficiency; Children; Adolescents

Outcome Measures

Primary Outcomes (1)

• Change in HOMA-IR

  Change in HOMA-IR from initial visit to end-of-study visit; i.e., the value at the later time point minus the value at the earlier time point. HOMA-IR= Fasting insulin (mIU/ml) x Fasting glucose (mg/dl) / 405.

  4-12 mo after randomization (4 months after target 25-hydroxyvitamin D level is reached).

Secondary Outcomes (2)

• Time to Normalization of Vit D Level Versus BMI Z Score

  1 to 12 months

• Change in BMI Z-score

  4-12 mo after randomization (4 months after target 25-hydroxyvitamin D level is reached).

Study Arms (3)

Control Group

ACTIVE COMPARATOR

Standard vitamin D3 dose as per IOM (Institute of Medicine) recommendations; actual dose will be 5000 IU per week, which is just slightly higher than the IOM recommendation of 600 IU per day. Length of time proposed to be 4 months at 5000 IU D3 per week. End of study measures at 4 months to be HOMA-IR, BMI Z score, 25-OHD level.

Drug: Vitamin D3

Low-Normal Group

EXPERIMENTAL

Initial D3 dose will be 30,000 IU per week; at 6 week intervals serum D3 levels will be checked, and dose adjustments made to reach target 25-OHD level of between 30-50 ng/mL (inclusive). Once within target, D3 dose will be continued for 4 months, and end of study measurements done (HOMA-IR, BMI Z score, 25-OHD level).

Drug: Vitamin D3

High-Normal Group

EXPERIMENTAL

Initial D3 dose will be 60,000 IU/week; at 6 week intervals 25-OHD levels will be done, and dose adjustments made to achieve target level of 40-60 ng/mL (inclusive). Once within target range, D3 dose will be continued for 4 months, and end of study measures obtained (HOMA-IR, BMI Z score, 25-OHD level).

Drug: Vitamin D3

Interventions

Vitamin D3 DRUG

Vitamin D3, liquid formulation, 5000 IU/mL.

Also known as: calcidiol

Control Group; High-Normal Group; Low-Normal Group

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• age 6-17 years
• BMI \> 95% for age
• serum 25-OH D level \< or + to 25 ng/mL

You may not qualify if:

• BMI \< 95% for age
• serum 25-OH D level \> 25 ng/mL
• current Vitamin D supplementation \> 400 IU/day
• anti-convulsant therapy, anti-hypertensive therapy, lipid lowering medication
• any medications that affect glucose metabolism (e.g., metformin, insulin)
• daily glucocorticoid therapy
• diabetes
• any disorders of bone or calcium metabolism
• hepatic or renal disease
• any malabsorptive disorder
• baseline serum Calcium \> 11 ng/dL (\> 2 SD above the mean)
• any genetic disorder that predisposes to obesity (e.g., Prader Willi
• hypothalamic obesity

Sponsors & Collaborators

• Perrin C White, MD: lead

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (9)

• Olson ML, Maalouf NM, Oden JD, White PC, Hutchison MR. Vitamin D deficiency in obese children and its relationship to glucose homeostasis. J Clin Endocrinol Metab. 2012 Jan;97(1):279-85. doi: 10.1210/jc.2011-1507. Epub 2011 Nov 9.

  PMID: 22072738 BACKGROUND

• Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011 Jan;96(1):53-8. doi: 10.1210/jc.2010-2704. Epub 2010 Nov 29.

  PMID: 21118827 BACKGROUND

• Mansbach JM, Ginde AA, Camargo CA Jr. Serum 25-hydroxyvitamin D levels among US children aged 1 to 11 years: do children need more vitamin D? Pediatrics. 2009 Nov;124(5):1404-10. doi: 10.1542/peds.2008-2041.

  PMID: 19951983 BACKGROUND

• Rajakumar K, Fernstrom JD, Holick MF, Janosky JE, Greenspan SL. Vitamin D status and response to Vitamin D(3) in obese vs. non-obese African American children. Obesity (Silver Spring). 2008 Jan;16(1):90-5. doi: 10.1038/oby.2007.23.

  PMID: 18223618 BACKGROUND

• Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006 Jul;84(1):18-28. doi: 10.1093/ajcn/84.1.18.

  PMID: 16825677 BACKGROUND

• Nagpal J, Pande JN, Bhartia A. A double-blind, randomized, placebo-controlled trial of the short-term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men. Diabet Med. 2009 Jan;26(1):19-27. doi: 10.1111/j.1464-5491.2008.02636.x.

  PMID: 19125756 BACKGROUND

• von Hurst PR, Stonehouse W, Coad J. Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient - a randomised, placebo-controlled trial. Br J Nutr. 2010 Feb;103(4):549-55. doi: 10.1017/S0007114509992017. Epub 2009 Sep 28.

  PMID: 19781131 BACKGROUND

• Alemzadeh R, Kichler J, Babar G, Calhoun M. Hypovitaminosis D in obese children and adolescents: relationship with adiposity, insulin sensitivity, ethnicity, and season. Metabolism. 2008 Feb;57(2):183-91. doi: 10.1016/j.metabol.2007.08.023.

  PMID: 18191047 BACKGROUND

• Maalouf J, Nabulsi M, Vieth R, Kimball S, El-Rassi R, Mahfoud Z, El-Hajj Fuleihan G. Short- and long-term safety of weekly high-dose vitamin D3 supplementation in school children. J Clin Endocrinol Metab. 2008 Jul;93(7):2693-701. doi: 10.1210/jc.2007-2530. Epub 2008 Apr 29.

  PMID: 18445674 BACKGROUND

MeSH Terms

Conditions

Obesity; Insulin Resistance; Vitamin D Deficiency

Interventions

Cholecalciferol; Calcifediol

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Avitaminosis; Deficiency Diseases; Malnutrition

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Hydroxycholecalciferols

Limitations and Caveats

Because of poor subject retention, there were insufficient outcome data to allow hypothesis testing.

Results Point of Contact

• Title: Dr Perrin C White, Professor of Pediatrics
• Organization: UT Southwestern Medical Center

perrin.white@utsouthwestern.edu

2146486875

Study Officials

• Michele R Hutchison, MD, PhD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: June 17, 2014
• First Posted: June 20, 2014
• Study Start: March 1, 2011
• Primary Completion: September 1, 2013
• Study Completion: October 11, 2015
• Last Updated: December 9, 2019
• Results First Posted: December 9, 2019

Record last verified: 2019-11

Locations

US (1)