Hypovitaminosis D : A Link Between Bone/Mineral and Fat/Fuel Metabolism

NCT01315366 | Completed Phase 3 DMC

• 2 other identifiers: AUBMC-GE-HF-1AUBMC-IM-GE-HF-20
• Study Type: interventional
• Target: 257
• Locations: 1 country
• Sites: 1

Brief Summary

The optimal dose of vitamin D needed to optimize beneficial effects on musculoskeletal outcomes remains to be defined. Equally unclear is the impact of vitamin D on fuel metabolism and insulin sensitivity in human subjects. Thus, the overall objective of this proposal is to test the hypothesis that in ambulatory overweight elderly individuals, vitamin D administration at doses higher than currently recommended will:

1. 1.Have a salutary effect on parameters of glucose and fuel metabolism. It will thus decrease indices of insulin resistance, improve lipid profile, and decrease markers of cardiovascular disease including adipokines, inflammatory cytokines, and markers of cell adhesion.
2. 2.Have a superior effect on indices of mineral and musculoskeletal metabolism, including bone remodeling markers, lean mass, and bone mineral density.

Conditions

Hypovitaminosis D; Insulin Resistance; Obesity; Osteoporosis

Keywords

Vitamin D; Elderly; Cardiovascular profile; Insulin resistance; Gene polymorphisms

Outcome Measures

Primary Outcomes (2)

• The HOMA index of insulin resistance

  A full assessment of insulin resistance will be performed,using the HOMA, McAuley and QUICKI indices. The impact of vitamin D on all outcomes of interest will be assessed by treatment arms and then in sub-group analyses: * by baseline levels of vit D-PTH at study entry: Vitamin D\< 20 ng/ml-PTH\>76pg/ml; vitamin D\<20ng/ml and PTH\<76 pg/ml, vitamin D\>20ng * by gender

  1 year

• Bone mineral density (BMD) at the spine,hip and total body measured by DXA and bone turnover markers (Osteocalcin and cross laps).

  We will measure the bone mineral density at the spine, hip and total body. We will also test the bone turnover markers as osteocalcin and cross laps.

  1 year

Secondary Outcomes (11)

• Insulin, C- peptide, Fasting glucose, Chemistries, Vitamin D metabolites, Vitamin D binding protein, Urinary Ca/Cr ratio ,serum lipids,inflammatory markers(IL-6, CRP),adhesion molecules (sVCAM), GLA-OC and GLU-OC.

  1 year

• Body fat mass and body lean mass measured by DXA

  1 year

• Serum DLk1 levels

  1 year

• Adiponectin Receptor expression and Leptin from subcutaneous fat and muscle biopsies at baseline and follow-up.

  1 year

• Morphologic bone assessment gathered defined by techniques incorporated into BMD acquisition scan image: Hip structural analyses parameters (Cortical thickness, Cross-sectional moment of inertia, section modulus) and trabecular bone structure (TBS)

  1 year

Study Arms (2)

High dose vitamin D

ACTIVE COMPARATOR

Ci-Cal D (1000mg/day) and vitamin D (500IU/day) Ci-Cal D daily, plus a supplement of vitamin D3 EuroD (20,000 IU/wk) for one year.

Dietary Supplement: Euro D and Ci-CalD

Low dose Vitamin D

PLACEBO COMPARATOR

Ci-Cal D (1000mg/day) and vitamin D (500IU/day) Ci-Cal D daily, plus a weekly placebo (EURO D Placebo) supplement for one year.

Dietary Supplement: Euro D, Ci-CalD

Interventions

Euro D and Ci-CalD DIETARY_SUPPLEMENT

Ci-Cal D (1000mg/day) and vitamin D (500IU/day) daily, plus a supplement of vitamin D3 (20,000 IU/wk) for one year.

Also known as: Europharm

High dose vitamin D

Euro D, Ci-CalD DIETARY_SUPPLEMENT

Ci-Cal D(1000mg/day) and vitamin D (500IU/day) Ci-CalD daily, plus a weekly placebo Euro D supplement for one year.

Also known as: EuroPharm

Low dose Vitamin D

Eligibility Criteria

• Age: 65 Years - 95 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may not qualify if:

• BMI ≥ 25Kg/meters squared
• Subjects with impaired glucose tolerance on no medications will not be excluded.
• The classification of individuals as diabetics or having impaired glucose tolerance will be based on the American Diabetes Association criteria for diagnosis.

Sponsors & Collaborators

• American University of Beirut Medical Center: lead
• Hotel Dieu de France Hospital: collaborator
• Rafic Hariri University Hospital: collaborator

Study Sites (1)

American University of Beirut

Beirut, 11-0236, Lebanon

Location

Related Publications (27)

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• Pittas AG, Harris SS, Stark PC, Dawson-Hughes B. The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults. Diabetes Care. 2007 Apr;30(4):980-6. doi: 10.2337/dc06-1994. Epub 2007 Feb 2.

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  PMID: 16551730 BACKGROUND

• Bacha DS, Rahme M, Al-Shaar L, Baddoura R, Halaby G, Singh RJ, Mahfoud ZR, Habib R, Arabi A, El-Hajj Fuleihan G. Vitamin D3 Dose Requirement That Raises 25-Hydroxyvitamin D to Desirable Level in Overweight and Obese Elderly. J Clin Endocrinol Metab. 2021 Aug 18;106(9):e3644-e3654. doi: 10.1210/clinem/dgab296.

  PMID: 33954783 DERIVED

• El Sabeh M, Ghanem P, Al-Shaar L, Rahme M, Baddoura R, Halaby G, Singh RJ, Vanderschueren D, Bouillon R, El-Hajj Fuleihan G. Total, Bioavailable, and Free 25(OH)D Relationship with Indices of Bone Health in Elderly: A Randomized Controlled Trial. J Clin Endocrinol Metab. 2021 Jan 23;106(2):e990-e1001. doi: 10.1210/clinem/dgaa780.

  PMID: 33280041 DERIVED

• Bassatne A, Jafari A, Kassem M, Mantzoros C, Rahme M, El-Hajj Fuleihan G. Delta-like 1 (DLK1) is a possible mediator of vitamin D effects on bone and energy metabolism. Bone. 2020 Sep;138:115510. doi: 10.1016/j.bone.2020.115510. Epub 2020 Jul 1.

  PMID: 32622071 DERIVED

• Rahme M, Al-Shaar L, Singh R, Baddoura R, Halaby G, Arabi A, Habib RH, Daher R, Bassil D, El-Ferkh K, Hoteit M, El-Hajj Fuleihan G. Limitations of platform assays to measure serum 25OHD level impact on guidelines and practice decision making. Metabolism. 2018 Dec;89:1-7. doi: 10.1016/j.metabol.2018.09.003. Epub 2018 Sep 15.

  PMID: 30227144 DERIVED

• Arabi A, Khoueiry-Zgheib N, Awada Z, Mahfouz R, Al-Shaar L, Hoteit M, Rahme M, Baddoura R, Halabi G, Singh R, El Hajj Fuleihan G. CYP2R1 polymorphisms are important modulators of circulating 25-hydroxyvitamin D levels in elderly females with vitamin insufficiency, but not of the response to vitamin D supplementation. Osteoporos Int. 2017 Jan;28(1):279-290. doi: 10.1007/s00198-016-3713-5. Epub 2016 Jul 30.

  PMID: 27473187 DERIVED

• El-Hajj Fuleihan G, Baddoura R, Habib RH, Halaby G, Arabi A, Rahme M, Singh RJ, Kassem M, Mahfoud Z, Hoteit M, Daher RT, Kassir MF. Effect of vitamin D replacement on indexes of insulin resistance in overweight elderly individuals: a randomized controlled trial. Am J Clin Nutr. 2016 Aug;104(2):315-23. doi: 10.3945/ajcn.116.132589. Epub 2016 Jul 13.

  PMID: 27413130 DERIVED

MeSH Terms

Conditions

Vitamin D Deficiency; Insulin Resistance; Obesity; Osteoporosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Ghada El Hajj Fuleihan, MD, MPH

  American University of Beirut Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 2, 2011
• First Posted: March 15, 2011
• Study Start: January 1, 2011
• Primary Completion: August 1, 2014
• Study Completion: July 1, 2015
• Last Updated: November 20, 2015

Record last verified: 2015-03

Locations

LE (1)