Effect of Milk Protein and Prebiotics in Combination With Vitamin D on Innate Immunity in Elderly People
Primary Purpose
Immunosenescence, Inflammation
Status
Completed
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Milk protein, prebiotics, vitamin D
Placebo product
Sponsored by

About this trial
This is an interventional basic science trial for Immunosenescence focused on measuring Immunity, Elderly, Inflammation, Milk protein, Prebiotics
Eligibility Criteria
Inclusion Criteria:
- Female
- Age 65-85 years
- BMI 20-30 kg/m2
- Non-smoking
- Generally healthy
- Regular and normal Dutch eating habits
- Veins suitable for cannulation (blood sampling)
- Voluntary participation
- Having given written informed consent
- Willing to comply with study procedures
- Accept use of all encoded data, including publication, and the confidential use and storage of all data for 15 years.
- Accept disclosure of the financial benefit of participation in the study to the authorities concerned
Exclusion Criteria:
- Having chronic inflammatory or autoimmune diseases such as rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease
- Disease of GI tract (including major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, bowel resection, known or suspected gastrointestinal disorders, colon or GI tract cancer), liver, gall bladder, kidneys, thyroid gland
- Immune-compromised
- Use of vitamin supplements containing vitamin D and not willing to discontinue this during the study
- Use of anti-inflammatory drugs (for corticosteroids and NSAIDs : frequency >1 per week)
- Use of immunosuppressive drugs
- Excessive alcohol usage (>3 consumptions/day or >15 consumptions/week)
- Participation in any clinical trial including blood sampling and/or administration of substances within 60 days before inclusion in this study
- Use of hormonal replacement therapy
- Mental status that is incompatible with the proper conduct of the study
- A self-reported milk allergy or sensitivity to dairy ingredients
- Unexplained weight loss or weight gain of > 3 kg in the 3 months prior to pre-study screening
- First and second degree relatives of personnel of NIZO food research or Wageningen University, department of Cell Biology and Immunology or Human Nutrition
- Not having a general practitioner
- Not willing to accept information-transfer concerning participation in the study, or information regarding his health, like laboratory results and eventual adverse events to and from his general practitioner
- Holiday to a sunny country during the study, starting from inclusion
- Light therapy during the study, starting from inclusion
- Use of prebiotic supplements during 2 months before study start, and during the study
Sites / Locations
- NIZO food research
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Nutritional intervention product
Placebo product
Arm Description
Milk protein, prebiotics, vitamin D
placebo product
Outcomes
Primary Outcome Measures
Cmax of ex vivo IFN-a production by PBMCs, corrected for baseline
Maximum IFN-a levels after 3, 6 and 9 weeks of treatment as compared to baseline in supernatant of PBMCs ex vivo stimulated with TLR ligands.
Cmax of ex vivo IL-6 production by PBMCs, corrected for baseline
Maximum IL-6 levels after 3, 6 and 9 weeks of treatment as compared to baseline in supernatant of PBMCs ex vivo stimulated with TLR ligands.
Secondary Outcome Measures
Cmax of ex vivo TNF-a production by PBMCs, corrected for baseline
Maximum TNF-a levels after 3, 6 and 9 weeks of treatment as compared to baseline in supernatant of PBMCs ex vivo stimulated with TLR ligands.
Change from baseline in percentage IFN-a producing pDCs
Percentage IFN-a-producing pDCs in PBMCs upon ex vivo stimulation with TLR ligands determined by flow cytometry
Change from baseline in percentage IL-6 producing pDCs
Percentage IL-6-producing pDCs in PBMCs upon ex vivo stimulation with TLR ligands determined by flow cytometry
Change from baseline in percentage TNF-a producing pDCs
Percentage TNF-a-producing pDCs in PBMCs upon ex vivo stimulation with TLR ligands determined by flow cytometry
Full Information
NCT ID
NCT03026244
First Posted
January 12, 2017
Last Updated
September 3, 2018
Sponsor
NIZO Food Research
Collaborators
FrieslandCampina, Wageningen University
1. Study Identification
Unique Protocol Identification Number
NCT03026244
Brief Title
Effect of Milk Protein and Prebiotics in Combination With Vitamin D on Innate Immunity in Elderly People
Official Title
A Nutritional Intervention Study to Evaluate the Effect of Milk Protein and Prebiotics in Combination With Vitamin D on Innate Immunity in Elderly People
Study Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
November 2016 (undefined)
Primary Completion Date
October 2017 (Actual)
Study Completion Date
October 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NIZO Food Research
Collaborators
FrieslandCampina, Wageningen University
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Rationale: The immune system in the ageing population becomes compromised with age (termed "Immunosenescence"). Therefore, elderly people have a decreased ability to respond to infection and vaccination. Furthermore, many of the health issues associated with ageing are linked to inflammation ("Inflammaging"). It has been suggested that this compromised immune function is in part due to reduced Toll-like receptor (TLR) function, which is part of the innate immune system. Milk and dairy based products have been shown to have beneficial effects on inflammation and immunity. This effect may be mediated via support of the innate immune response and promotes TLR7 signaling in in vitro assays (unpublished observation). Also prebiotics have been suggested to influence markers of innate immune function. Furthermore, TLR function has been suggested to be correlated to vitamin D status. Therefore, in the current pilot study, the potential of milk protein, prebiotics and vitamin D to support innate immune function in elderly will be investigated.
Objective: Aim of the current study is to evaluate the effect of milk protein on the innate immune response in elderly in a pilot study. Furthermore, support of this effect by prebiotics and Vitamin D will be studied.
Study design: The study will be a double-blind placebo-controlled pilot study. Study population: Healthy female elderly subjects of 65-85 years of age. Intervention: Period 1: Milk protein or placebo. Period 2: Milk protein + prebiotics or placebo. Period 3: Milk protein + prebiotics + Vitamin D or placebo.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Immunosenescence, Inflammation
Keywords
Immunity, Elderly, Inflammation, Milk protein, Prebiotics
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Nutritional intervention product
Arm Type
Active Comparator
Arm Description
Milk protein, prebiotics, vitamin D
Arm Title
Placebo product
Arm Type
Placebo Comparator
Arm Description
placebo product
Intervention Type
Dietary Supplement
Intervention Name(s)
Milk protein, prebiotics, vitamin D
Intervention Description
3 weeks supplementation with milk protein only, followed by 3 weeks milk protein + prebiotics, followed by 3 weeks milk protein + prebiotics + vitamin D
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo product
Intervention Description
3 periods of 3 weeks placebo product
Primary Outcome Measure Information:
Title
Cmax of ex vivo IFN-a production by PBMCs, corrected for baseline
Description
Maximum IFN-a levels after 3, 6 and 9 weeks of treatment as compared to baseline in supernatant of PBMCs ex vivo stimulated with TLR ligands.
Time Frame
baseline, 3 weeks, 6 weeks, 9 weeks
Title
Cmax of ex vivo IL-6 production by PBMCs, corrected for baseline
Description
Maximum IL-6 levels after 3, 6 and 9 weeks of treatment as compared to baseline in supernatant of PBMCs ex vivo stimulated with TLR ligands.
Time Frame
baseline, 3 weeks, 6 weeks, 9 weeks
Secondary Outcome Measure Information:
Title
Cmax of ex vivo TNF-a production by PBMCs, corrected for baseline
Description
Maximum TNF-a levels after 3, 6 and 9 weeks of treatment as compared to baseline in supernatant of PBMCs ex vivo stimulated with TLR ligands.
Time Frame
baseline, 3 weeks, 6 weeks, 9 weeks
Title
Change from baseline in percentage IFN-a producing pDCs
Description
Percentage IFN-a-producing pDCs in PBMCs upon ex vivo stimulation with TLR ligands determined by flow cytometry
Time Frame
baseline, and highest percentage at either 3 weeks, 6 weeks, or 9 weeks of treatment
Title
Change from baseline in percentage IL-6 producing pDCs
Description
Percentage IL-6-producing pDCs in PBMCs upon ex vivo stimulation with TLR ligands determined by flow cytometry
Time Frame
baseline, and highest percentage at either 3 weeks, 6 weeks, or 9 weeks of treatment
Title
Change from baseline in percentage TNF-a producing pDCs
Description
Percentage TNF-a-producing pDCs in PBMCs upon ex vivo stimulation with TLR ligands determined by flow cytometry
Time Frame
baseline, and highest percentage at either 3 weeks, 6 weeks, or 9 weeks of treatment
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
65 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Female
Age 65-85 years
BMI 20-30 kg/m2
Non-smoking
Generally healthy
Regular and normal Dutch eating habits
Veins suitable for cannulation (blood sampling)
Voluntary participation
Having given written informed consent
Willing to comply with study procedures
Accept use of all encoded data, including publication, and the confidential use and storage of all data for 15 years.
Accept disclosure of the financial benefit of participation in the study to the authorities concerned
Exclusion Criteria:
Having chronic inflammatory or autoimmune diseases such as rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease
Disease of GI tract (including major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, bowel resection, known or suspected gastrointestinal disorders, colon or GI tract cancer), liver, gall bladder, kidneys, thyroid gland
Immune-compromised
Use of vitamin supplements containing vitamin D and not willing to discontinue this during the study
Use of anti-inflammatory drugs (for corticosteroids and NSAIDs : frequency >1 per week)
Use of immunosuppressive drugs
Excessive alcohol usage (>3 consumptions/day or >15 consumptions/week)
Participation in any clinical trial including blood sampling and/or administration of substances within 60 days before inclusion in this study
Use of hormonal replacement therapy
Mental status that is incompatible with the proper conduct of the study
A self-reported milk allergy or sensitivity to dairy ingredients
Unexplained weight loss or weight gain of > 3 kg in the 3 months prior to pre-study screening
First and second degree relatives of personnel of NIZO food research or Wageningen University, department of Cell Biology and Immunology or Human Nutrition
Not having a general practitioner
Not willing to accept information-transfer concerning participation in the study, or information regarding his health, like laboratory results and eventual adverse events to and from his general practitioner
Holiday to a sunny country during the study, starting from inclusion
Light therapy during the study, starting from inclusion
Use of prebiotic supplements during 2 months before study start, and during the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Els van Hoffen, PhD
Organizational Affiliation
NIZO Food Research
Official's Role
Principal Investigator
Facility Information:
Facility Name
NIZO food research
City
Ede
ZIP/Postal Code
6718 ZB
Country
Netherlands
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
30515164
Citation
van Splunter M, Perdijk O, Fick-Brinkhof H, Feitsma AL, Floris-Vollenbroek EG, Meijer B, Brugman S, Savelkoul HFJ, van Hoffen E, van Neerven RJJ. Bovine Lactoferrin Enhances TLR7-Mediated Responses in Plasmacytoid Dendritic Cells in Elderly Women: Results From a Nutritional Intervention Study With Bovine Lactoferrin, GOS and Vitamin D. Front Immunol. 2018 Nov 20;9:2677. doi: 10.3389/fimmu.2018.02677. eCollection 2018.
Results Reference
derived
Learn more about this trial
Effect of Milk Protein and Prebiotics in Combination With Vitamin D on Innate Immunity in Elderly People
We'll reach out to this number within 24 hrs