PRIMAGE (Probiotics, Immunity and Ageing)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2011 by University of Reading.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
University of Reading
ClinicalTrials.gov Identifier:
NCT01066377
First received: February 9, 2010
Last updated: July 12, 2011
Last verified: July 2011
  Purpose

Ageing dramatically affects immune function; this phenomenon is known as immunosenescence and partly explains the increased susceptibility for infection in older individuals. Vaccination is recommended to protect older people against influenza, but immunosenescence also reduces the efficacy of vaccination. Probiotics are beneficial bacteria, which can be consumed and which have a long and safe record of use in humans. Often they are taken together with prebiotics, which are carbohydrates that provide a food source for the beneficial bacteria when they reach the lower gut. There is particular interest in the positive influences of pre- and probiotics in older people, who are subject to alteration in gut microflora composition as well as immunosenescence.

The PRIMAGE (Probiotics, immunity and ageing) study will examine the effect of a prebiotic and probiotic mix on the immune response to influenza vaccination in young and older subjects, and is funded by BBSRC DRINC. It will involve 60 young (18-35y) and 60 older (65-85y) subjects recruited from the local Reading community. Participants will take a pre- and probiotic mixture or a placebo for a total of 8 weeks. The probiotic is not currently commercially produced, but has been demonstrated to have particular ecological fitness and anti-pathogenic effects in the gastrointestinal tract in old age. A suitable prebiotic will be selected on the basis of ability to promote optimal growth and survival of this probiotic. After 4 weeks on the treatment, the subjects will receive an influenza vaccination. Blood, saliva and stool samples will be taken before treatment, and at 4, 6 and 8 weeks after commencement. The samples taken at 6 and 8 weeks will be used to assess the immune response to the vaccination. A wide range of immune parameters will be assessed, taking into account the age-related shifts in immune cell populations.


Condition Intervention
Influenza
Dietary Supplement: Prebiotic and probiotic mix

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Official Title: A Randomised, Controlled, Parallel Study to Determine the Immunomodulatory Effects of Pre- and Probiotics Upon the Immune Response to Influenza Vaccination in Young and Older Volunteers

Resource links provided by NLM:


Further study details as provided by University of Reading:

Primary Outcome Measures:
  • The immune response to influenza vaccination among young and older adults [ Time Frame: 4 weeks after vaccination ] [ Designated as safety issue: No ]
    Serum vaccine-specific antibodies to the 2010-2011 influenza vaccine will be measured by hemagglutination assay.


Secondary Outcome Measures:
  • The cellular and molecular basis for modulation of immune function by pre- and probiotics. [ Time Frame: Assessed after 4 weeks of pre- and probiotic treatment ] [ Designated as safety issue: No ]
    Blood samples will be subject to density gradient separation of peripheral blood mononuclear cells (PBMC), and cryopreserved for NK cell analysis, cell phenotypes, cytokine production, proliferation, expression of activation markers, expression of toll like receptors and assessment of T cell receptor excision circles (TREC). Serum and plasma will be stored for measurement of chemokines, plasma lipids and glucose. Saliva samples will be used to assess salivary IgA content.

  • The cellular and molecular basis for modulation of immune function by pre- and probiotics. [ Time Frame: Assessed after 6 weeks of pre- and probiotic treatment ] [ Designated as safety issue: No ]
    Blood samples will be subject to density gradient separation of peripheral blood mononuclear cells (PBMC), and cryopreserved for NK cell analysis, cell phenotypes, cytokine production, proliferation, expression of activation markers, expression of toll like receptors and assessment of T cell receptor excision circles (TREC). Serum and plasma will be stored for measurement of chemokines, plasma lipids and glucose. Saliva samples will be used to assess salivary IgA content.

  • The cellular and molecular basis for modulation of immune function by pre- and probiotics. [ Time Frame: Assessed after 8 weeks of pre- and probiotic treatment ] [ Designated as safety issue: No ]
    Blood samples will be subject to density gradient separation of peripheral blood mononuclear cells (PBMC), and cryopreserved for NK cell analysis, cell phenotypes, cytokine production, proliferation, expression of activation markers, expression of toll like receptors and assessment of T cell receptor excision circles (TREC). Serum and plasma will be stored for measurement of chemokines, plasma lipids and glucose. Saliva samples will be used to assess salivary IgA content.

  • The modulation of the gut microbiota by pre- and probiotics. [ Time Frame: Assessed after 4 weeks of pre- and probiotic treatment ] [ Designated as safety issue: No ]
    Faecal samples will be processed for later analysis by fluorescence in situ hybridization (FISH) using oligonucleotide 16s rRNA probes targeting dominant and important groups of gut bacteria. Denatured gradient gel electrophoresis (DGGE) will be used to assess changes in faecal bacterial abundance and species diversity. qPCR will be used to identify specific bacterial species, including Bifidobacterium longum. Faecal dry weight and IgA content will be assessed. Faecal content of microbial metabolites such as short chain fatty acids and ammonia will be quantified.

  • The modulation of the gut microbiota by pre- and probiotics. [ Time Frame: Assessed after 8 weeks of pre- and probiotic treatment ] [ Designated as safety issue: No ]
    Faecal samples will be processed for later analysis by fluorescence in situ hybridization (FISH) using oligonucleotide 16s rRNA probes targeting dominant and important groups of gut bacteria. Denatured gradient gel electrophoresis (DGGE) will be used to assess changes in faecal bacterial abundance and species diversity. qPCR will be used to identify specific bacterial species, including Bifidobacterium longum. Faecal dry weight and IgA content will be assessed. Faecal content of microbial metabolites such as short chain fatty acids and ammonia will be quantified.


Estimated Enrollment: 120
Study Start Date: April 2010
Estimated Study Completion Date: January 2013
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Prebiotic and probiotic mix
Prebiotic: 8g/day, will be selected on the basis of ability to promote optimal growth and survival of the probiotic (inulin, fructooligosaccharides [FOS], galactooligosaccharides[GOS] and xylooligosaccharides[XOS] will be tested). Probiotic: 10^8 - 10^9 live bacteria/day, bifidobacterium longum bv. infantis CCUG52486.
Dietary Supplement: Prebiotic and probiotic mix
The probiotic strain will be Bifidobacterium longum bv. infantis CCUG 52486 (10^8 - 10^9 live bacteria per day), which was originally isolated from healthy elderly subjects, and which has been demonstrated to have particular ecological fitness and anti-pathogenic effects in vitro. A suitable prebiotic (8g/day) will be selected on the basis of ability to promote optimal growth and survival of this probiotic (inulin, fructooligosaccharides [FOS], galactooligosaccharides[GOS] and xylooligosaccharides[XOS] will be tested).
Other Names:
  • Bifidobacterium lactentis
  • Bifidobacterium liberorum
  • Bifidobacterium infantis
  • Bifidobacterium longum infantis
  • Bifidobacterium longum subsp. infantis
  • oligofructose
  • oligofructan
  • oligogalactosyllactose
  • oligogalactose
  • oligolactose
  • transgalactooligosacchariden
Placebo Comparator: Maltodextrin/milk powder Dietary Supplement: Prebiotic and probiotic mix
The probiotic strain will be Bifidobacterium longum bv. infantis CCUG 52486 (10^8 - 10^9 live bacteria per day), which was originally isolated from healthy elderly subjects, and which has been demonstrated to have particular ecological fitness and anti-pathogenic effects in vitro. A suitable prebiotic (8g/day) will be selected on the basis of ability to promote optimal growth and survival of this probiotic (inulin, fructooligosaccharides [FOS], galactooligosaccharides[GOS] and xylooligosaccharides[XOS] will be tested).
Other Names:
  • Bifidobacterium lactentis
  • Bifidobacterium liberorum
  • Bifidobacterium infantis
  • Bifidobacterium longum infantis
  • Bifidobacterium longum subsp. infantis
  • oligofructose
  • oligofructan
  • oligogalactosyllactose
  • oligogalactose
  • oligolactose
  • transgalactooligosacchariden

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Suitable study participants will be defined as:

  • aged 18-35 (young cohort) or 65-85 (older cohort) men and women
  • BMI 18.5 - 30 kg/m2
  • good general health as determined by medical questionnaires and laboratory data from screening blood and urine sample (fasting glucose, ESR, FBC, liver function tests, renal profile, dipstick urinalysis)
  • not pregnant, lactating or planning a pregnancy

Exclusion Criteria:

  • allergy to the influenza vaccine
  • HIV infection
  • diabetes requiring any medication
  • asplenia and other acquired or congenital immunodeficiencies
  • any autoimmune disease
  • malignancy
  • cirrhosis
  • connective tissue diseases
  • current use of immunomodulating medication (including oral prednisone and inhaled steroids)
  • self-reported symptoms of acute or recent infection (including use of antibiotics within last 3 months)
  • taking lactulose or any other treatment for constipation
  • alcoholism and drug misuse

Additional exclusion criteria for older volunteers includes:

  • laboratory data which is outside the normal range for this age group AND outside the ranges specified in the SENIEUR protocol for ESR, FBC, renal profile, liver function tests, fasting glucose and dipstick urinalysis (Ligthart et al, 1984)
  • Barthel Index score of <16
  • CIRS score of <15.

Additional exclusion criteria for younger volunteers is:

  • laboratory data which is outside the normal range
  • influenza vaccination in the previous 12 months.
  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: NCT01066377

Locations
United Kingdom
University of Reading
Reading, United Kingdom, RG6 6AP
Sponsors and Collaborators
University of Reading
Investigators
Principal Investigator: Parveen Yaqoob University of Reading
  More Information

No publications provided

Responsible Party: Dr Mike Proven, University of Reading
ClinicalTrials.gov Identifier: NCT01066377     History of Changes
Other Study ID Numbers: BB/H00470X/1
Study First Received: February 9, 2010
Last Updated: July 12, 2011
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University of Reading:
prebiotic
probiotic
influenza
vaccination
ageing
immunosenescence

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Sulfalene
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Infective Agents, Urinary
Renal Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on August 21, 2014