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Prebiotics and Immune Function in Middle Aged Humans

This study has been completed.
Sponsor:
Collaborator:
University of Southampton
Information provided by:
University Hospital Southampton NHS Foundation Trust.
ClinicalTrials.gov Identifier:
NCT00898599
First received: April 20, 2009
Last updated: July 28, 2010
Last verified: July 2010
  Purpose

Prebiotics are naturally occurring carbohydrates found in a variety of edible plants. They are not digested by mammalian enzymes, and so reach the gut intact, where they are fermented by some species of intestinal bacteria. This fermentation is thought to have several benefits for the host including improving immune function. There are numerous methods available for assessing the human immune response. Response to vaccination is thought to be a good method for this. Not many studies have examined the effect of prebiotics on the human immune response to vaccination. Thus the investigators propose to test the effect of a prebiotic on the immune response in healthy volunteers including their response to the current flu vaccine. The investigators hypothesise that the prebiotic will enhance the immune response including the response to the vaccine.


Condition Intervention Phase
Immune Function
Dietary Supplement: Prebiotic
Dietary Supplement: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Investigation of the Effects of a Prebiotic Supplement on Immune Function in Healthy Human Adults

Further study details as provided by University Hospital Southampton NHS Foundation Trust.:

Primary Outcome Measures:
  • Serum anti-vaccine antibody concentrations [ Time Frame: Weeks 2 and 4 post-vaccination ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Serum total antibody (IgG, IgA, IgM) concentrations [ Time Frame: Weeks -4, 0, 2 and 4 with respect to vaccination ] [ Designated as safety issue: No ]
  • Innate immune responses - neutrophil and monocyte phagocytosis and respiratory burst [ Time Frame: Weeks -4, 0, 2 and 4 with respect to vaccination ] [ Designated as safety issue: No ]
  • Ex vivo T lymphocyte responses to mitogen (activation, proliferation and cytokine production) [ Time Frame: Weeks -4, 0, 2 and 4 with respect to vaccination ] [ Designated as safety issue: No ]
  • Ex vivo T lymphocyte responses to vaccine (activation, proliferation and cytokine production) [ Time Frame: Weeks 0, 2 and 4 with respect to vaccination ] [ Designated as safety issue: No ]
  • Ex vivo natural killer cell activity [ Time Frame: Weeks -4, 0, 2 and 4 with respect to vaccination ] [ Designated as safety issue: No ]
  • Faecal microflora [ Time Frame: Weeks -4 and 0 with respect to vaccination ] [ Designated as safety issue: No ]
  • Salivary IgA concentration [ Time Frame: Weeks -4, 0, 2 and 4 with respect to vaccination ] [ Designated as safety issue: No ]

Enrollment: 49
Study Start Date: April 2009
Study Completion Date: July 2010
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Maltodextrin Dietary Supplement: Placebo
Maltodextrin as placebo
Other Name: Maltodextrin
Experimental: Prebiotic
Inulin type fructooligosaccharides
Dietary Supplement: Prebiotic
Inulin type fructooligosaccharides
Other Name: Synergy1

Detailed Description:

Prebiotics are naturally occurring carbohydrates found in a variety of edible plants. They are not digested by mammalian enzymes, and so reach the gut intact, where they are fermented by some species of intestinal bacteria. This fermentation is thought to have several benefits for the host including improving the immune response. Inulin-type fructans (oligofructose and inulin) are classified as prebiotics. Inulin is found naturally in significant amounts in a variety of plants foods, such as bananas, leeks, onions, artichokes, wheat and chicory. Synergy1 is a prebiotic preparation produced by Beneo-Orafti, and containing a mixture of oligofructose and inulin derived from chicory. Fructooligosaccharides including Synergy1 are widely used by the food industry and are commonly found as a source of insoluble fibre in many biscuit, bakery, cereal and dairy products.

There is increasing evidence that the changes in the intestinal microflora that occur with the consumption of fructooligosaccharides can modulate immune parameters, not only in the gut-associated lymphoid tissue, but also secondary lymphoid tissues and the peripheral circulation. Much of the evidence for beneficial effects of fructooligosaccharides on immune function comes from animal models e.g. rats, mice, dogs and pigs. Results from these studies show that the innate and adaptive immune systems of both the gut associated lymphoid tissue and the systemic immune system can be modified by fructooligosaccharides. However, there are few human studies so far which have investigated the effects of prebiotics on immune function, and these studies mostly rely on systemic markers of immunity. The results show little effect of fructooligosaccharides on innate immune function, but mixed results are reported regarding the adaptive immune system, suggesting that there may by improvement on this aspect of immunity with increased intake of fructooligosaccharides. The small number of published human studies led Watzl et al. (2005) to suggest that more human studies are needed to find out whether inulin and/or oligofructose have the potential to modulate systemic immunity in well-nourished individuals.

There are numerous methods available for assessing the human immune response. These have been evaluated by a panel of European experts (Albers et al. 2005). Based on its biological relevance, sensitivity and practical feasibility, response to vaccination was identified by this panel as the gold standard for measuring the functioning of the immune system in vivo (Albers et al. 2005). A small number of studies have studied the effect of fructooligosaccharides on the human immune response using vaccination response as the outcome, but only four of these examined fructooligosaccharides in the absence of other additional nutrients and of these two studies were in infants. Thus, the number of studies examining the immunologic impact of fructooligosaccharides in adult humans and using the gold standard outcome is very limited. From a public health perspective, it would be of importance, if fructooligosaccharides can improve immune function especially in older adults who are at risk of age-related immune decline. Thus, we propose to use a commercially available influenza vaccine (Imuvac®) to stimulate the immune response in healthy human adults, and to use this to assess the effect of a well defined prebiotic preparation commonly used in the food industry (Synergy1).

  Eligibility

Ages Eligible for Study:   45 Years to 66 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Aged 45-65 years
  2. Body mass index 20 to 32 kg/m2.
  3. Not consuming probiotic supplements, yoghurts, drinks or other foods
  4. Not consuming prebiotic supplemented drinks or foods
  5. In general good health
  6. No antibiotic use in the 2 months prior to entering the study or during the study
  7. Not been vaccinated with the current season's influenza vaccine
  8. Being able to provide written informed consent

Exclusion Criteria:

  1. Aged < 45 or > 66 years
  2. Body mass index < 20 or > 32 kg/m2.
  3. Being diabetic (type 1 or type 2)
  4. Displaying manifestations of allergy - asthma, hay-fever, dermatitis - or being treated for these
  5. Being egg allergic
  6. Use of any prescribed medicine (unless deemed to be acceptable by the PI)
  7. Suffering from any infectious illness
  8. Chronic gastrointestinal problems (e.g. IBD, IBS, cancer)
  9. Recent blood donation
  10. Participation in another clinical trial
  11. Use of prebiotic or probiotic supplements, foods or drinks
  12. Consuming vitamin, mineral or oil supplements
  13. Previously vaccinated with the influenza vaccine being used.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00898599

Locations
United Kingdom
University of Southampton
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
University Hospital Southampton NHS Foundation Trust.
University of Southampton
Investigators
Principal Investigator: Philip C Calder, PhD University of Southampton
  More Information

No publications provided

Responsible Party: Philip Calder, University of Southampton
ClinicalTrials.gov Identifier: NCT00898599     History of Changes
Other Study ID Numbers: RHMNUT0055
Study First Received: April 20, 2009
Last Updated: July 28, 2010
Health Authority: United Kingdom: National Health Service

ClinicalTrials.gov processed this record on November 24, 2014