Effect of Milk Protein and Prebiotics in Combination With Vitamin D on Innate Immunity in Elderly People

NCT03026244 | Completed

• 1 other identifier: NL57345.081.16
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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 This effect may be mediated via support of the innate immune response and promotes TLR7 signaling in in vitro assays (unpublished observation).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.

Conditions

Immunosenescence; Inflammation

Keywords

Immunity; Elderly; Inflammation; Milk protein; Prebiotics

Outcome Measures

Primary Outcomes (2)

• 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.

  baseline, 3 weeks, 6 weeks, 9 weeks

• 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.

  baseline, 3 weeks, 6 weeks, 9 weeks

Secondary Outcomes (4)

• Cmax of ex vivo TNF-a production by PBMCs, corrected for baseline

  baseline, 3 weeks, 6 weeks, 9 weeks

• Change from baseline in percentage IFN-a producing pDCs

  baseline, and highest percentage at either 3 weeks, 6 weeks, or 9 weeks of treatment

• Change from baseline in percentage IL-6 producing pDCs

  baseline, and highest percentage at either 3 weeks, 6 weeks, or 9 weeks of treatment

• Change from baseline in percentage TNF-a producing pDCs

  baseline, and highest percentage at either 3 weeks, 6 weeks, or 9 weeks of treatment

Study Arms (2)

Nutritional intervention product

ACTIVE COMPARATOR

Milk protein, prebiotics, vitamin D

Dietary Supplement: Milk protein, prebiotics, vitamin D

Placebo product

PLACEBO COMPARATOR

placebo product

Dietary Supplement: Placebo product

Interventions

Milk protein, prebiotics, vitamin D DIETARY_SUPPLEMENT

3 weeks supplementation with milk protein only, followed by 3 weeks milk protein + prebiotics, followed by 3 weeks milk protein + prebiotics + vitamin D

Nutritional intervention product

Placebo product DIETARY_SUPPLEMENT

3 periods of 3 weeks placebo product

Placebo product

Eligibility Criteria

• Age: 65 Years - 85 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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
• Use of prebiotic supplements during 2 months before study start, and during the study

Sponsors & Collaborators

• NIZO Food Research: lead
• FrieslandCampina: collaborator
• Wageningen University: collaborator

Study Sites (1)

NIZO food research

Ede, 6718 ZB, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 30515164 DERIVED

MeSH Terms

Conditions

Inflammation

Interventions

Milk Proteins; Prebiotics; Vitamin D

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Animal Proteins, Dietary; Dietary Proteins; Proteins; Amino Acids, Peptides, and Proteins; Food; Diet, Food, and Nutrition; Physiological Phenomena; Milk; Dairy Products; Food and Beverages; Dietary Fiber; Dietary Carbohydrates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Dietary Supplements; Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Els van Hoffen, PhD

  NIZO Food Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2017
• First Posted: January 20, 2017
• Study Start: November 1, 2016
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: September 5, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)