NCT02553044

Brief Summary

Total 25(OH)D is currently used as a biomarker of vitamin D status. However, there is some debate as to whether total 25(OH)D is the best marker to use. It has been suggested that free vitamin D may be better because it may be more biologically available. There are also some uncertainties about how we treat vitamin D deficiency. A single dose is attractive because it is certain that the patient has had the dose and there is no requirement for ongoing compliance, but it is still not clear what the best dose is to give. Also, recent studies have highlighted that high dose vitamin D supplementation may increase the risk of falling in older populations. The investigators believe that studying how free vitamin D responds to different bolus doses is the best way address some of the current research gaps, including what is the best biomarker of vitamin D status, what is the mechanism of vitamin D toxicity and what is a safe bolus dose to treat deficiency. The investigators will study changes in total and free 25(OH)D, and also clinical response, to three different bolus doses of vitamin D (50 000IU, 150 000IU and 500 000IU) in 84 vitamin D deficient postmenopausal women, over a three month period with 5 study visits. A concurrent control group of 28 vitamin D sufficient postmenopausal women will also be recruited. This will allow the investigators to determine how total and free vitamin D change with bolus dosing and whether there is a disproportionate rise in free 25(OH)D with higher doses that may lead to hypercalcemia and falls.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
112

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Oct 2015

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 16, 2015

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 17, 2015

Completed
14 days until next milestone

Study Start

First participant enrolled

October 1, 2015

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2018

Completed
Last Updated

February 15, 2019

Status Verified

February 1, 2019

Enrollment Period

2.8 years

First QC Date

September 16, 2015

Last Update Submit

February 12, 2019

Conditions

Vitamin D DeficiencyOsteoporosis

Outcome Measures

Primary Outcomes (1)

  • Free 25(OH)D

    Change in free 25(OH)D from baseline to visit 3 (5-7 days after administration)

    Baseline to visit 3 (5-7 days after administration)

Secondary Outcomes (13)

  • Proportion of total 25(OH)D to free 25(OH)D

    5(+/-2) days, 28(+/-3) days and 84(+/-5) days

  • 1, 25(OH)2D

    5(+/-2) days, 28(+/-3) days and 84(+/-5) days

  • Ionized calcium

    5(+/-2) days, 28(+/-3) days and 84(+/-5) days

  • Parathyroid Hormone

    5(+/-2) days, 28(+/-3) days and 84(+/-5) days

  • Bone turnover marker - Alkaline Phosphatase

    5(+/-2) days, 28(+/-3) days and 84(+/-5) days

  • +8 more secondary outcomes

Study Arms (4)

50 000IU Vitamin D3

EXPERIMENTAL

50 000IU oral vitamin D3 (cholecalciferol) administered at baseline only.

Dietary Supplement: Cholecalciferol (Vitamin D3)

150 000IU Vitamin D3

EXPERIMENTAL

150 000IU oral vitamin D3 (cholecalciferol) administered at baseline only.

Dietary Supplement: Cholecalciferol (Vitamin D3)

500 000IU Vitamin D3

EXPERIMENTAL

500 000IU oral vitamin D3 (cholecalciferol) administered at baseline only.

Dietary Supplement: Cholecalciferol (Vitamin D3)

Concurrent Control

NO INTERVENTION

Control group to receive no intervention.

Interventions

Cholecalciferol (Vitamin D3)DIETARY_SUPPLEMENT

Oral vitamin D3 doses made up using 50 000IU ampules of vitamin D3 dissolved in 1ml of olive oil.

Also known as: Invita D3
150 000IU Vitamin D350 000IU Vitamin D3500 000IU Vitamin D3

Eligibility Criteria

Age55 Years+
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Caucasian
  • (OH)D \< 30nmol/l for treatment groups or 25(OH)D \>50nmol/l for control group
  • BMI between 20 kg/m2 and 30kg/m2
  • years and over and postmenopausal (at least 5 years since last menstrual period)
  • Able and willing to participate in the study and provide written informed consent.

You may not qualify if:

  • History of any long term immobilization (duration greater than three months)
  • Pre-diagnosed diabetes mellitus
  • High trauma fracture or low trauma fracture less than one year prior to recruitment
  • History of or current conditions known to affect vitamin D or bone metabolism, including:
  • Chronic renal disease Malabsorption syndromes Diagnosed endocrine disorders Hypercalcaemia Diagnosed restrictive eating disorder
  • Use of medications or treatment known to affect vitamin D or bone metabolism such as bisphosphonates or anti-epileptic medication.
  • Alcohol intake of greater than 21 units per week
  • Holiday with significant sunlight exposure in the last six weeks
  • Planned sun holiday within study period
  • Abnormal clinical laboratory parameters that are assessed as clinically significant by the PI.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Clinical Research Facility

Sheffield, South Yorkshire, S5 7AU, United Kingdom

Location

Related Publications (4)

  • Shibli-Rahhal A, Paturi B. Variations in parathyroid hormone concentration in patients with low 25 hydroxyvitamin D. Osteoporos Int. 2014 Jul;25(7):1931-6. doi: 10.1007/s00198-014-2687-4. Epub 2014 Mar 20.

    PMID: 24647889BACKGROUND

  • Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010 May 12;303(18):1815-22. doi: 10.1001/jama.2010.594.

    PMID: 20460620BACKGROUND

  • Powe CE, Ricciardi C, Berg AH, Erdenesanaa D, Collerone G, Ankers E, Wenger J, Karumanchi SA, Thadhani R, Bhan I. Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res. 2011 Jul;26(7):1609-16. doi: 10.1002/jbmr.387.

    PMID: 21416506BACKGROUND

  • Bhan I, Powe CE, Berg AH, Ankers E, Wenger JB, Karumanchi SA, Thadhani RI. Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients. Kidney Int. 2012 Jul;82(1):84-9. doi: 10.1038/ki.2012.19. Epub 2012 Mar 7.

    PMID: 22398410BACKGROUND

MeSH Terms

Conditions

Vitamin D DeficiencyOsteoporosis

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

AvitaminosisDeficiency DiseasesMalnutritionNutrition DisordersNutritional and Metabolic DiseasesBone Diseases, MetabolicBone DiseasesMusculoskeletal DiseasesMetabolic Diseases

Intervention Hierarchy (Ancestors)

CholestenesCholestanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSterolsVitamin DSecosteroidsMembrane LipidsLipids

Study Officials

  • Jennifer Walsh, MBChB, PhD

    University of Sheffield

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 16, 2015

First Posted

September 17, 2015

Study Start

October 1, 2015

Primary Completion

August 1, 2018

Study Completion

August 1, 2018

Last Updated

February 15, 2019

Record last verified: 2019-02

Locations

GB(1)