Importance of Dosing Regimen for the Effect of Vitamin D Supplementation

Vitamin D is a hormone with effects not only on the skeleton, but on most tissues in the body. Lack of vitamin D is associated with cardio-vascular disease (CVD), type 2 diabetes, cancer, infectious and immunological diseases, as well as risk factors for these diseases. However, intervention studies with vitamin D have been inconclusive regarding diseases and risk factors. This could be due to inclusion of subjects already vitamin D sufficient, and short and underpowered studies. In addition, there are indications that the dosing regimens may be important, so that daily doses with vitamin D are more efficient than intermittent doses, which so far have been generally used. This could be related to the concentration of circulating and thereby intracellular vitamin D concentrations, which probably is dependent on daily vitamin D doses. This will be tested in the present study where 60 subjects will be randomized to vitamin D 160 000 once, vitamin D 4000 IU/day, or placebo for four weeks. The primary endpoints will be effects on serum hepcidin and plasma cathelicidin after 4 weeks, with effects on serum PTH, RNA expression and microRNA in peripheral blood, telomerase activity in peripheral blood mononuclear cells and the ration between serum 1,25(OH)2D and 24,25(OH)2D as secondary endpoints.

Study Overview

• Status: Completed
• Conditions: Hypovitaminosis D
• Intervention / Treatment: Drug: Vitamin D; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 3

Contacts and Locations

Study Locations

• Norway
  • Tromsø, Norway, 9038
    • University Hospital of North Norway

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:- Males and females 20 - 70 years

• 20 kg/m2 > BMI < 35 kg/m2
• systolic BP < 175 mmHg, diastolic BP < 105 mmHg
• Serum 25(OH)D level < 50 nmol/L. Serum 25(OH)D < 50 nmol/L is considered as vitamin D deficiency, and accordingly, effects of vitamin D supplementation will be easier to detect than if the included subjects were vitamin D sufficient.
• Hgb, SR, CRP, creatinine < 130 umol/L in males, < 120 umol/L in females, calcium, FT4 and TSH within the normal reference range; ASAT < 90 mU/L ALAT < 140 U/L, HbA1c < 6.6 %
• The subjects must agree not to take any vitamin D supplementation, including cod liver oil or "mølje", use solarium or go on sunny vacation during the intervention period.

Exclusion Criteria:

• subjects allergic to peanuts
• subjects with primary hyperparathyroidism
• granulomatous diseases (sarcoidosis, tuberculosis, Wegner's granulomatosis)
• diabetes
• renal stones the last five years
• subjects seriously ill (or with chronic disease) and unfit for participation in the study (as judged by one of the study doctors)
• subjects using vitamin D supplements exceeding 800 IU per day or active vitamin D drugs (Rocaltrol or Etalpha)
• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: vitamin D bolus; vitamin D 160 000 IU given as bolus	Drug: Vitamin D; vitamin D given as bolus versus daily dosing
Experimental: vitamin D daily; vitamin D 4000 IU daily for 28 days	Drug: Vitamin D; vitamin D given as bolus versus daily dosing
Placebo Comparator: placebo; identical looking as vitamin d	Drug: Placebo; identical looking as vitamin D

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepcidin change	Difference between vitamin D given as a bolus 160 000IU vs 4000 IU regarding change in serum hepcidin	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in serum PTH after 1 month	Difference between vitamin D given as a bolus 160 000IU vs 4000 IU regarding change in serum PTH, cathelicidin, RNA expression and micro RNA in peripheral blood, telomerase activity and the ratio between 1,25(OH)2D and 24,25(OH)2D, after 1 month	4 weeks
Difference in micro RNA Expression after 1 month	Difference between vitamin D given as a bolus 160 000IU vs 4000 IU	4 weeks
Difference in serum cathelicidin after 1 month	Difference between vitamin D given as a bolus 160 000IU vs 4000 IU	4 weeks
Difference in RNA Expression after 1 month	Difference between vitamin D given as a bolus 160 000IU vs 4000 IU	4 weeks
Difference in telomerase Activity after 1 month	Difference between vitamin D given as a bolus 160 000IU vs 4000 IU	4 weeks
Difference in ratio between 1,24(OH)2D and 24,24(OH)2D after 1 month	Difference between vitamin D given as a bolus 160 000IU vs 4000 IU	4 weeks

Collaborators and Investigators

• Sponsor: University of Tromso
• Investigators: Principal Investigator: rolf jorde, MD PhD, UiT, Tromsø

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2017
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: June 15, 2017
• First Submitted That Met QC Criteria: September 1, 2017
• First Posted (Actual): September 5, 2017

Study Record Updates

• Last Update Posted (Actual): May 24, 2018
• Last Update Submitted That Met QC Criteria: May 23, 2018
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: vitamin D
• Additional Relevant MeSH Terms: Metabolic Diseases; Nutrition Disorders; Musculoskeletal Diseases; Deficiency Diseases; Malnutrition; Bone Diseases; Bone Diseases, Metabolic; Calcium Metabolism Disorders; Vitamin D Deficiency; Rickets; Avitaminosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: TromsøEndo-2017-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No