Clinical trial NCT02924246: Effect of Milk on the Vaccination Response
Official title: MOSAIC-2: Effect of Raw Milk on the Immune Response Upon Cholera Vaccination
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infection
Keywords: immunity
vaccination
milk
Lead sponsor: NIZO Food Research
Sponsor class: OTHER
Collaborators: name: FrieslandCampina
First posted: 2016-10-05
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Rationale: Oral vaccination is known to induce a systemic immune response as well as an immune response in mucosal tissues, and can therefore serve as a model to study systemic and mucosal immunity. In this study, the oral cholera vaccine Dukoral® was chosen as model vaccine. The kinetics of the immune response and the interaction with a raw milk matrix have been evaluated in a previous, pilot study (NL49042.081.14). Based on the outcomes of this pilot, in this study oral cholera vaccination will be applied to study the support of immunity by raw milk, compared to heat-treated milk. The study design has been optimised based on previous results: study duration is extended and sample size is based on relevant change and known variation in the primary outcome parameters.

Infections are an important worldwide cause of death, both in elderly and young children. Therefore, support of immunity could help to reduce the incidence of infections. To screen the potential of specific foods or food ingredients to support immunity, oral vaccination can serve as a model. In a previous study, this model was developed using oral cholera vaccination in human adult volunteers. In that study, raw milk was shown to support the immune response to vaccination. In this follow-up study, the effect of raw milk will be compared with pasteurized and ultra-heat treated (UHT) milk.

Objective: To investigate whether pasteurized milk and/or UHT milk are able to enhance the immune response as induced by oral cholera vaccination, in comparison to raw milk and to regular vaccination.

Study design: The study is designed as a single-blind randomized controlled trial of 6 weeks.

Study population: Healthy subjects of 18-50 years of age.

Interventions: 1) Raw milk, obtained from farms that comply to the high quality requirements for production of raw milk, and that has been screened according to the safety criteria for raw milk; 2) commercially available full-fat UHT milk; 3) commercially available full-fat pasteurized milk.


Eligibility criteria: Inclusion Criteria:

* Age 18-50 yr
* Signed informed consent
* Availability of internet connection
* Male or female
* Willing to stop blood donation at the blood bank during the study period

Exclusion Criteria:

* Currently participating in another clinical trial
* Previous Cholera, Salmonella, or E. coli vaccination
* Tonsillectomy
* Acute gastroenteritis in the past 2 months
* Use of antibiotics in the past 2 months
* Hypersensitivity to the vaccine, to formaldehyde or to any of the excipients (sodium salts)
* Pregnancy or lactating
* Not willing to drink raw milk
* Allergic to milk or lactose-intolerant
* Disease of GI tract, liver, gall bladder, kidneys, thyroid gland
* Immune-compromised
* Use of immunosuppressive drugs
* Drug abuse, and not willing/able to stop this during the study
* Excessive alcohol usage (men: \>4 consumptions/day or \>20 consumptions/week; women: \>3 consumptions/day or \>15 consumptions/week)

Primary outcomes:
measure: Change in cholera toxin-specific IgA and IgG antibody level in serum as a marker of the vaccination response
timeFrame: baseline and day 14, 28, 42
Secondary outcomes:
measure: Change in the cholera toxin-specific IgA and IgG antibody level in nasal wash as a marker of the vaccination response
timeFrame: baseline and day 14, 28, 42
measure: Change in the cholera toxin-specific IgA and IgG antibody level in saliva as a marker of the vaccination response
timeFrame: baseline and day 14, 28, 42
measure: Change in the cholera toxin-specific IgA antibody level in feces as a marker of the vaccination response
timeFrame: baseline and day 14, 28, 42
Other outcomes:
measure: Change in the expression of intestinal and mucosal homing markers on IgA and IgG antibody-secreting B cells in peripheral blood, measured by flow cytometry, as markers of the route of modulation of the vaccination response
timeFrame: baseline and day 14
measure: Cholera toxin-specific T cell proliferation as marker of modulation of the vaccination response
timeFrame: baseline and day 14
Locations:
city: Ede
country: Netherlands
facility: NIZO food research
Study officials:
affiliation: NIZO Food Research
name: Els van Hoffen, PhD
role: PRINCIPAL_INVESTIGATOR
References: