Vitamin D Supplementation and the Immune Response

Impact of Vitamin D Supplementation on Immune Functions: Study in Subjects Aged Over 65 Years Vaccinated Against Influenza

The main objective is to assess the variation in plasma levels of cathelicidin before and after influenza vaccination.

All bibliographic data suggests that supplementation vitamin D in the elderly often deficient in this vitamin may have a double interest:

• By induction of cathelicidin, assist in anti-infective response in particular to the influenza virus
• The normalization of vitamin D status, promote the return to an appropriate immune response limiting excess inflammation and improving capacity to respond.

The entire project will collect new information on the merits of the use of vitamin D in aging. A better knowledge of mechanisms involved and the impact of aging on them is a necessary prerequisite the definition of a new strategy using this drug in the elderly particularly fragile in order to improve its autonomy. This definition seems a sociological interest obvious economic knowing the current aging population and its impact future of our health system.

Study Overview

• Status: Terminated
• Conditions: D Vitamin Deficiency Patients
• Intervention / Treatment: Drug: Vitamin D (drug)

Detailed Description

CONDUCT OF THE STUDY:

Visit 1: selection of subjects (CPC / CIC-Inserm CIC501)

• Medical Examination, clinical examination, explanation of the protocol and collection of written consent,
• Collection of anthropometric data measured size and not declarative weight form examination, measurement of current weight, BMI, waist circumference measurement.
• Food Survey.
• Fasting blood sampling: for dosing of vitamin D, cathelicidin, exploration of immunocompetent cells, calcium, phosphorus, urea and creatinine.

Visit 2: randomization (CPC / CIC-Inserm CIC501)

• Fasting blood sampling: for dosing of vitamin D, cathelicidin, and the serum calcium, phosphorus, urea and creatinine.
• Exploration of immune cells in patients deficient in vitamin D (molecular and cellular analyzes).

Start of vitamin D supplementation or placebo

• Subjects with vitamin D levels <30ng/mL will be randomized into two groups:

  • Arm receiving vitamin D (BS).
  • Arm receiving placebo (BC).
• It will be given to the patient 4 bulbs product (vitamin D or placebo) for supplementation for 2 months (1 / 15 days).

Call subjects at 4 weeks of vitamin supplementation / placebo to assess the clinical safety of the product, as well as compliance with the instructions of supplementation.

Visit 3: After seven weeks of vitamin supplementation / placebo (CPC / CIC-Inserm CIC501)

• Fasting blood assay for vitamin D and calcium collection.
• urinary dosage calcium. Visit 4: Month 2 (CPC / CIC-Inserm CIC501)
• Validation of laboratory measurements made by an independent medical M2 protocol.
• Delivery of products to test for the third month of vitamin supplementation / placebo.

For the placebo group given two bulbs for the third month placebo placebo supplementation.

For the VitD group: dose adjustment according to the following scheme:

• If [25(OH) D]> 75 ng / ml and / or calcium levels> 106 mg / ml and / or calcium excretion> 300 mg / l: presentation of two bulbs placebo.
• If [25(OH) D] <75 ng / ml and serum calcium <106 mg / ml and calcium excretion <300 mg / l: presentation of two ampoules of Vitamin D. Visit 5 - Month 3 vaccination INTANZA 15 ® (3 months after the start of supplementation)
• Recovery of boxes and empty ampoules of vitamin D.
• Evaluation of the clinical safety of vitamin D.
• Collection of anthropometric data: measurement of current weight and BMI,
• Fasting blood sampling: for dosing of vitamin D, cathelicidin, exploration of immunocompetent cells, calcium, phosphorus, urea and creatinine.
• Influenza serology, Visit 6 - Month 4: end of study
• Clinical examination with assessment of tolerability of vaccination and delivery of the form of reporting due to immunization and infectious complications side effects according to the criteria of toxicity CTCNCI Bethesda,
• Collection of anthropometric data: measurement of current weight, calculating the weight change,
• Fasting blood sampling: for dosing of vitamin D, cathelicidin, exploration of immunocompetent cells, calcium, phosphorus, urea and creatinine.
• Measurement of seroconversion, seroprotection, MGT antibodies following vaccination.

End of the study Removal of anonymity for physician investigators to propose a vitamin D the subjects who received placebo.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63003
    • CHU clermont-ferrand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 85 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- Aged 65 or over subject,

• Subjects with a vitamin D levels below 30 ng / ml,
• Acceptance of vitamin D (100 000 IU of UVEDOSE ®)
• Acceptance of influenza vaccination with INTANZA15 ®
• Affiliation to a social security scheme
• The subject agrees not to change their eating habits

Exclusion Criteria:

• Liver disease: cirrhosis, chronic hepatitis.
• Renal impairment whatever degree
• Hypercalcemia (serum calcium> 2.6 mol / l)
• Hypo-or hyperparathyroidism history, history of renal colic.
• Disease / acute infection, moderate or severe (at the discretion of the investigator) on the day of vaccination or febrile illness (temperature ≥ 38 ° C). The subject should not be included in the study as his condition is not cured or her fever has not gone down).
• Long-term treatment with bisphosphonates, corticosteroids, anti-inflammatory, anticonvulsant, antiepileptics, fibrates.
• Known hypersensitivity to vitamin D
• Prior supplementation (in the last year) or supplementation of vitamin D during
• Participation at the time of inclusion in the trial, or planned participation during the same period that this trial, another trial on a vaccine, drug, medical device.
• Vaccination during the 4 weeks prior to vaccination or immunization of the test set out in the three weeks after vaccination test.
• Transfusion of immunoglobulins, blood or blood products during the last 3 months
• Congenital or acquired, known or suspected immunodeficiency, immunosuppressive therapy in the last 6 months, such as cancer chemotherapy or radiotherapy; steroids long-term systemic (prednisone or equivalent for more than two consecutive weeks in the Previous 3 months).
• Systemic Hypersensitivity to any component of the vaccine (ovalbumin, chicken protein, neomycin, formaldehyde, octoxinol 9), or a history of reaction to influenza vaccine or a vaccine containing one of the substances in the vaccine trial, which involved life-threatening.
• Deprivation of liberty or by administrative order issued by a court, subject to emergency medical or involuntary hospitalization.
• Topic enjoying a measure of legal protection (guardianship, guardianship ...).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: vitamin D; The entire project will collect new information on the merits of the use of vitamin D in aging. A better knowledge of mechanisms involved and the impact of aging on them is a necessary prerequisite the definition of a new strategy using this drug in the elderly particularly fragile in order to improve its autonomy. This definition seems a sociological interest obvious economic knowing the current aging population and its impact future of our health system	Drug: Vitamin D (drug)
Other: INTANZA 15; The entire project will collect new information on the merits of the use of vitamin D in aging. A better knowledge of mechanisms involved and the impact of aging on them is a necessary prerequisite the definition of a new strategy using this drug in the elderly particularly fragile in order to improve its autonomy. This definition seems a sociological interest obvious economic knowing the current aging population and its impact future of our health system	Drug: Vitamin D (drug)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
levels of cathelicidin	at Month 3

Secondary Outcome Measures

Outcome Measure	Time Frame
Levels of plasma 25(OH) D	Day 0, week 7 and Month 3.
Levels of pro-inflammatory cytokines and anti-inflammatory (IL-4, IL-5, IL-10, IL-13, IL-17, IL-23, TFN, IFN and TGF)	Day 0, week 7 and Month 3.
Rate of seroconversion, seroprotection, the MGT antibodies	Day 0, week 7 and Month 3.

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Investigators: Principal Investigator: Henri LAURICHESSE, University Hospital, Clermont-Ferrand

Publications and helpful links

General Publications

• Goncalves-Mendes N, Talvas J, Duale C, Guttmann A, Corbin V, Marceau G, Sapin V, Brachet P, Evrard B, Laurichesse H, Vasson MP. Impact of Vitamin D Supplementation on Influenza Vaccine Response and Immune Functions in Deficient Elderly Persons: A Randomized Placebo-Controlled Trial. Front Immunol. 2019 Feb 8;10:65. doi: 10.3389/fimmu.2019.00065. eCollection 2019.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: June 25, 2013
• First Submitted That Met QC Criteria: July 2, 2013
• First Posted (Estimate): July 9, 2013

Study Record Updates

• Last Update Posted (Estimate): December 23, 2015
• Last Update Submitted That Met QC Criteria: December 22, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: elderly; supplementation; vitamin D; influenza vaccine; immunocompetente cells, immune system
• Additional Relevant MeSH Terms: Nutrition Disorders; Deficiency Diseases; Malnutrition; Vitamin D Deficiency; Avitaminosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: CHU-0160; 2012-005658-52