Pilot Pharmacokinetic Study of Daily Versus Monthly High-Dose Cholecalciferol Supplementation

NCT01079923 | Completed DMC

• 1 other identifier: 09-007602
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Research has shown that Vitamin D is important in preventing rickets in children, osteomalacia in adults, certain cancers, cardiovascular disease, Type 2 Diabetes, and metabolic syndrome. Data suggests that Vitamin D deficiency is common throughout the world. With increasing medical conditions being linked to Vitamin D deficiency, it is suggested that establishing early normal Vitamin D levels is important to long term health. There are low quantities of maternal Vitamin D that transfer from blood into breast milk. This places nursing infants at risk of developing low Vitamin D levels, and the American Academy of Pediatrics recommends they receive 400 international units (IU) of Vitamin D daily. If nursing mothers were supplemented with oral Vitamin D, this may produce adequate total Vitamin D in the breast milk for the growing infant to consume. By taking this potential therapeutic approach, this would prevent the burden of administering an oral Vitamin D liquid supplement to an infant. Recent laboratory technology now allows measurement of total Vitamin D (parent Vitamin D2 plus parent Vitamin D3). The main objective of this pilot study is to compare total Vitamin D levels resulting from daily Vitamin D supplementation of 5,000 international units of cholecalciferol (Vitamin D3) orally for 28 days vs. 150,000 international units of cholecalciferol orally once in healthy, non-pregnant, non-lactating female subjects aged 18 � 40. The research results will be used to help identify an optimal dosing regimen to administer to lactating mothers to hopefully deliver adequate total Vitamin D in nursing infants. This separate study will be conducted at a later date under a subsequent protocol. Previous research has demonstrated that Vitamin D3 levels become undetectable within 14 days after adult subjects received 100,000 international units of cholecalciferol. The investigators' central hypothesis is that daily dosing of 5,000 international units of cholecalciferol orally will maintain detectable total Vitamin D levels in serum after fourteen days, compared to high-dose 150,000 international units of oral cholecalciferol once. It is anticipated the aims of this pilot study will yield the following results. First, we, the investigators, hope to determine the resulting Vitamin D blood levels and calculate an appropriate dosing strategy for future research. Next we plan to measure the resulting 25,hydroxyvitamin D levels that correspond with these dosing regimens, since 25,hydroxyvitamin D is the major indicator of Vitamin D status in humans. Lastly, we will measure blood calcium and phosphorus levels to assure these doses of Vitamin D are tolerated by healthy female subjects.

Conditions

Healthy Volunteers

Keywords

healthy volunteers; healthy subjects; vitamin D; cholecalciferol; vitamin D3; total vitamin D

Outcome Measures

Primary Outcomes (1)

• Vitamin D pharmacokinetics

  Characterize the differences in pharmacokinetics of oral Vitamin D3 between two dosing regimens within women of child-bearing age by evaluating any changes in the number of days of detectable total serum Vitamin D and area under the curve (AUC) above baseline.

  28 days

Secondary Outcomes (3)

• Vitamin D Supplementation Dosing Regimen

  28 days

• Vitamin D Supplementation Dosing Regimen Efficacy

  28 days

• Vitamin D Supplementation Safety

  28 days

Study Arms (2)

Single High Dose Supplementation

ACTIVE COMPARATOR

Age 18 to 40 years, non-pregnant, non-lactating, female subjects .

Dietary Supplement: Single High Dose Cholecalciferol

Daily Dose Supplementation

ACTIVE COMPARATOR

Age 18 to 40 years, non-pregnant, non-lactating, female subjects.

Dietary Supplement: Daily Dose Cholecalciferol

Interventions

Single High Dose Cholecalciferol DIETARY_SUPPLEMENT

Age 18 to 40 years, non-pregnant, non-lactating, female subjects will receive cholecalciferol 150,000 international units orally once (Bio-tech Pharmacal 50,000 IU capsule, Fayetteville, AR).

Also known as: Vitamin D3

Single High Dose Supplementation

Daily Dose Cholecalciferol DIETARY_SUPPLEMENT

Age 18 to 40 years, non-pregnant, non-lactating, female subjects will receive cholecalciferol 5,000 IU capsule, Fayetteville, AR).

Also known as: Vitamin D3

Daily Dose Supplementation

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 to 40 years
• non-pregnant
• non-lactating
• female
• willing to participate in study with adequate compliance and follow-up

You may not qualify if:

• Any clinically significant underlying chronic disease states (i.e. diabetes, asthma, seizure disorders, hypo/hyperthyroidism, hypercalcemia, hypophosphatemia, other endocrine disorders, absorption disorders)
• allergy to study medication or its components
• significant travel south of the 35° North latitude in the 28-day study period
• chronic use of steroids, anti-convulsants, or barbiturates
• participation in indoor tanning practices during the 28-day study period

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (13)

• Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004 Mar;79(3):362-71. doi: 10.1093/ajcn/79.3.362.

  PMID: 14985208 BACKGROUND

• Ford ES, Ajani UA, McGuire LC, Liu S. Concentrations of serum vitamin D and the metabolic syndrome among U.S. adults. Diabetes Care. 2005 May;28(5):1228-30. doi: 10.2337/diacare.28.5.1228. No abstract available.

  PMID: 15855599 BACKGROUND

• Foss YJ. Vitamin D deficiency is the cause of common obesity. Med Hypotheses. 2009 Mar;72(3):314-21. doi: 10.1016/j.mehy.2008.10.005. Epub 2008 Dec 2.

  PMID: 19054627 BACKGROUND

• Suskind DL. Nutritional deficiencies during normal growth. Pediatr Clin North Am. 2009 Oct;56(5):1035-53. doi: 10.1016/j.pcl.2009.07.004.

  PMID: 19931062 BACKGROUND

• Heaney RP, Armas LA, Shary JR, Bell NH, Binkley N, Hollis BW. 25-Hydroxylation of vitamin D3: relation to circulating vitamin D3 under various input conditions. Am J Clin Nutr. 2008 Jun;87(6):1738-42. doi: 10.1093/ajcn/87.6.1738.

  PMID: 18541563 BACKGROUND

• Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J Clin Nutr. 2007 Jan;85(1):6-18. doi: 10.1093/ajcn/85.1.6.

  PMID: 17209171 BACKGROUND

• Mastaglia SR, Mautalen CA, Parisi MS, Oliveri B. Vitamin D2 dose required to rapidly increase 25OHD levels in osteoporotic women. Eur J Clin Nutr. 2006 May;60(5):681-7. doi: 10.1038/sj.ejcn.1602369.

  PMID: 16391587 BACKGROUND

• Ilahi M, Armas LA, Heaney RP. Pharmacokinetics of a single, large dose of cholecalciferol. Am J Clin Nutr. 2008 Mar;87(3):688-91. doi: 10.1093/ajcn/87.3.688.

  PMID: 18326608 BACKGROUND

• Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003 Jan;77(1):204-10. doi: 10.1093/ajcn/77.1.204.

  PMID: 12499343 BACKGROUND

• Thacher TD, Obadofin MO, O'Brien KO, Abrams SA. The effect of vitamin D2 and vitamin D3 on intestinal calcium absorption in Nigerian children with rickets. J Clin Endocrinol Metab. 2009 Sep;94(9):3314-21. doi: 10.1210/jc.2009-0018. Epub 2009 Jun 30.

  PMID: 19567516 BACKGROUND

• Saadi HF, Dawodu A, Afandi B, Zayed R, Benedict S, Nagelkerke N, Hollis BW. Effect of combined maternal and infant vitamin D supplementation on vitamin D status of exclusively breastfed infants. Matern Child Nutr. 2009 Jan;5(1):25-32. doi: 10.1111/j.1740-8709.2008.00145.x.

  PMID: 19161542 BACKGROUND

• Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. doi: 10.1210/jc.2004-0360.

  PMID: 15531486 BACKGROUND

• Taylor SN, Wagner CL, Hollis BW. Vitamin D supplementation during lactation to support infant and mother. J Am Coll Nutr. 2008 Dec;27(6):690-701. doi: 10.1080/07315724.2008.10719746.

  PMID: 19155428 BACKGROUND

MeSH Terms

Interventions

Single Person; Cholecalciferol

Intervention Hierarchy (Ancestors)

Marital Status; Family Characteristics; Demography; Population Characteristics; Socioeconomic Factors; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Bernard R Lee, PharmD, BCPS

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Thomas D Thacher, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Michael E Meekins, PharmD

  Mayo Clinic

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 2, 2010
• First Posted: March 3, 2010
• Study Start: February 1, 2010
• Primary Completion: April 1, 2010
• Study Completion: June 1, 2010
• Last Updated: November 20, 2012

Record last verified: 2012-11

Locations

US (1)