Taxifolin/Ergothioneine and Immune Biomarkers in Healthy Volunteers (TaxEr)

Influenza Clinical Trial

— TaxEr  

Official title:

A Pilot Study of Dietary Taxifolin/Dihydroquercetin and Ergothioneine and Immune Biomarkers in Healthy Volunteers

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05190432
• Other study ID #: ERGO61222.A1
• Status: Active, not recruiting
• Phase: N/A
• Start date: November 10, 2021
• Est. completion date: August 2024

Study information

• Verified date: May 2024
• Source: University of Southampton
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The complexities of the immune system make measuring the impact of dietary interventions upon its function challenging. The immune system is highly responsive to environmental influences, including the diet. An individual's diet provides the energy required to mount a strong and protective immune response, the building blocks required for synthesis of immune mediators such as antibodies and cytokines, and can also indirectly affect immune function via changes in the gut microbiome. Immune function varies across the lifecourse, with a well understood decline in immune function with age, resulting in impaired vaccination responses and an increased risk of infections and of severe complications and mortality arising from common communicable diseases such as influenza. This impaired immunity with ageing is known as immunosenescence and this affects both innate and acquired arms of the immune system.

Description:

Expert guidance is available to inform the design of human nutrition trials to ensure they include the most relevant immunological outcomes (Albers, 2013). In this study, ex vivo phagocytosis and oxidative burst of immune cells will be the primary outcome, supported by other ex vivo immune measures of high clinical relevance including functional assessment of cytokine production and expression of activation markers.

Human nutritional trials frequently omit to monitor the degree of immunosenescence in participants, even amongst studies conducted amongst older adults. For example, a recent review of pre- and probiotic trials which assessed immune responses in older adults identified that only two of thirty-six studies assessed any marker of immunosenescence (Childs & Calder, 2017).

Taxifolin/DHQ is a naturally occurring polyphenol found in apples, onions and other fruits and bark extracts. Ergothioneine is an amino acid found in mushrooms, oats and some bean varieties. We hypothesise that Taxifolin/DHQ and/or Ergothioneine will alter immune function via their established antioxidant effects, and that the effects observed will vary between older adults relative to their degree of immunosenescence.

Though current dietary guidelines advise consumption of 5 portions of fruits and vegetables per day, recent surveys reveal that fewer than 30% of adults achieve this. Antioxidants found within fruits and vegetables are understood to be one of the important aspects by which our diet can influence health. It is important to investigate the effects of such antioxidants through well designed and conducted human trials.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 90
• Est. completion date: August 2024
• Est. primary completion date: September 29, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 65 Years

Eligibility

Inclusion Criteria:

• age 50-65yr

• BMI 18.5-30kg/m2

• Willing to avoid consumption of foods rich in Taxifolin/DHQ and Ergothioneine during the study period

• Willing to avoid taking any other food supplements or high doses of vitamins during the study period

• Able to provide written informed consent.

Exclusion Criteria:

• Use of prescription medication which may influence immune function, such as anti-inflammatory or immunosuppressant medication

• Diabetes requiring any medication

• Liver cirrhosis

• A history of drug or alcohol misuse

• Asplenia or other acquired or congenital immunodeficiencies

• Any autoimmune disease including connective tissue diseases

• Malignancy

• Laboratory confirmed SARS-CoV-2 infection within last 3 months

• self-reported symptoms of acute or recent infection (including use of antibiotics within the last 3 months)

Related Conditions & MeSH terms

• Aging
• Cold
• Inflammation
• Influenza

Intervention

Dietary Supplement:
• Taxifolin
A naturally occurring polyphenol found in apples, onions and other fruits and bark extracts.
• Ergothioneine
An amino acid found in mushrooms, oats and some bean varieties.
• Control
Microcrystalline cellulose.

Locations

Country	Name	City	State
United Kingdom	NIHR Southampton Biomedical Research Centre	Southampton	Hampshire

Sponsors (2)

Lead Sponsor	Collaborator
University of Southampton	Blue California

Country where clinical trial is conducted

United Kingdom, 

References & Publications (9)

Albers R, Bourdet-Sicard R, Braun D, Calder PC, Herz U, Lambert C, Lenoir-Wijnkoop I, Meheust A, Ouwehand A, Phothirath P, Sako T, Salminen S, Siemensma A, van Loveren H, Sack U. Monitoring immune modulation by nutrition in the general population: identifying and substantiating effects on human health. Br J Nutr. 2013 Aug;110 Suppl 2:S1-30. doi: 10.1017/S0007114513001505. — View Citation

Childs, C. E., & Calder, P. C. (2017). Modifying the gut microbiome through diet: effects on the immune system of elderly subjects. In T. Fulop, C. Franceschi, K. Hirokawa, & G. Pawelec (Eds.), Handbook of Immunosenescence Cham: Springer International Publishing AG. DOI: 10.1007/978-3-319-64597-1_160-1

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Turck D, Bresson JL, Burlingame B, Dean T, Fairweather-Tait S, Heinonen M, Hirsch-Ernst KI, Mangelsdorf I, McArdle HJ, Naska A, Neuhauser-Berthold M, Nowicka G, Pentieva K, Sanz Y, Siani A, Sjodin A, Stern M, Tome D, Vinceti M, Willatts P, Engel KH, Marchelli R, Poting A, Poulsen M, Schlatter J, Gelbmann W, Van Loveren H. Scientific Opinion on taxifolin-rich extract from Dahurian Larch (Larix gmelinii). EFSA J. 2017 Feb 14;15(2):e04682. doi: 10.2903/j.efsa.2017.4682. eCollection 2017 Feb. — View Citation

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Turck D, Bresson JL, Burlingame B, Dean T, Fairweather-Tait S, Heinonen M, Hirsch-Ernst KI, Mangelsdorf I, McArdle HJ, Naska A, Neuhauser-Berthold M, Nowicka G, Pentieva K, Sanz Y, Siani A, Sjodin A, Stern M, Tome D, Vinceti M, Willatts P, Engel KH, Marchelli R, Poting A, Poulsen M, Schlatter JR, Ackerl R, van Loveren H. Statement on the safety of synthetic l-ergothioneine as a novel food - supplementary dietary exposure and safety assessment for infants and young children, pregnant and breastfeeding women. EFSA J. 2017 Nov 13;15(11):e05060. doi: 10.2903/j.efsa.2017.5060. eCollection 2017 Nov. — View Citation

Ey J, Schomig E, Taubert D. Dietary sources and antioxidant effects of ergothioneine. J Agric Food Chem. 2007 Aug 8;55(16):6466-74. doi: 10.1021/jf071328f. Epub 2007 Jul 6. — View Citation

Kang M, Ragan BG, Park JH. Issues in outcomes research: an overview of randomization techniques for clinical trials. J Athl Train. 2008 Apr-Jun;43(2):215-21. doi: 10.4085/1062-6050-43.2.215. — View Citation

Przemska-Kosicka A, Childs CE, Enani S, Maidens C, Dong H, Dayel IB, Tuohy K, Todd S, Gosney MA, Yaqoob P. Effect of a synbiotic on the response to seasonal influenza vaccination is strongly influenced by degree of immunosenescence. Immun Ageing. 2016 Mar 15;13:6. doi: 10.1186/s12979-016-0061-4. eCollection 2016. — View Citation

Taves DR. Minimization: a new method of assigning patients to treatment and control groups. Clin Pharmacol Ther. 1974 May;15(5):443-53. doi: 10.1002/cpt1974155443. No abstract available. — View Citation

Vega-Villa KR, Remsberg CM, Ohgami Y, Yanez JA, Takemoto JK, Andrews PK, Davies NM. Stereospecific high-performance liquid chromatography of taxifolin, applications in pharmacokinetics, and determination in tu fu ling (Rhizoma smilacis glabrae) and apple (Malus x domestica). Biomed Chromatogr. 2009 Jun;23(6):638-46. doi: 10.1002/bmc.1165. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phagocytosis activity by granulocytes ex vivo	Mean fluorescence intensity per cell will be assessed by flow cytometry.	8 weeks post intervention
Secondary	Percentage phagocytosis by monocytes ex vivo	Percentage of cells undergoing phagocytosis will be assessed by flow cytometry.	4 weeks, 8 weeks, 3 months post intervention
Secondary	Phagocytosis activity by monocytes ex vivo	Mean fluorescence intensity per cell will be assessed by flow cytometry.	4 weeks, 8 weeks, 3 months post intervention
Secondary	Percentage phagocytosis by granulocytes ex vivo	Percentage of cells undergoing phagocytosis will be assessed by flow cytometry.	4 weeks, 8 weeks, 3 months post intervention
Secondary	Phagocytosis activity by granulocytes ex vivo	Mean fluorescence intensity per cell will be assessed by flow cytometry.	4 weeks, 3 months post intervention
Secondary	Percentage oxidative burst by monocytes ex vivo	Percentage of cells undergoing oxidative burst will be assessed by flow cytometry.	4 weeks, 8 weeks, 3 months post intervention
Secondary	Oxidative burst activity by monocytes ex vivo	Mean fluorescence intensity per cell will be assessed by flow cytometry.	4 weeks, 8 weeks, 3 months post intervention
Secondary	Percentage oxidative burst by granulocytes ex vivo	Percentage of cells undergoing oxidative burst will be assessed by flow cytometry.	4 weeks, 8 weeks, 3 months post intervention
Secondary	Oxidative burst activity by granulocytes ex vivo	Mean fluorescence intensity per cell will be assessed by flow cytometry.	4 weeks, 8 weeks, 3 months post intervention
Secondary	Frequencies of naive T cells	The proportion of naive T cells will be assessed by flow cytometry.	8 weeks
Secondary	Frequencies of memory T cells	The proportion of memory T cells will be assessed by flow cytometry.	8 weeks
Secondary	CD57 expression upon T cells.	The proportion of T cells expressing CD57 (a marker associated with chronic immune activation) and the mean fluorescence intensity per cell will be assessed by flow cytometry.	8 weeks
Secondary	CD28 expression upon T cells.	The proportion of T cells expressing CD28 (a cell surface marker required for T cell activation and survival) and the mean fluorescence intensity per cell will be assessed by flow cytometry.	8 weeks
Secondary	Plasma lipid peroxides	Participant plasma lipid peroxides will be measured by colorimetric analysis.	8 weeks
Secondary	Urinary isoprostanes	Participant urinary isoprostanes will be measured by commercially available ELISA.	4 weeks, 8 weeks, 3 months post intervention
Secondary	Plasma isoprostanes	Participant plasma isoprostanes will be measured by commercially available ELISA.	4 weeks, 8 weeks, 3 months post intervention
Secondary	Cytokine production by cryopreserved peripheral blood mononuclear cells in response to lipopolyssaccharide	A panel of pro- and anti-inflammatory cytokines secreted by immune cells ex vivo will be assessed by Luminex array.	4 weeks, 8 weeks
Secondary	Cytokine production by cryopreserved peripheral blood mononuclear cells in response to influenza or coronavirus vaccine products	A panel of pro- and anti-inflammatory cytokines secreted by immune cells ex vivo will be assessed by Luminex array.	4 weeks, 8 weeks
Secondary	Metabolomic analysis of urine samples	Full metabolic profiling of first-morning urine samples will be used to assess changes to metabolic activity of participants and their microbiome.	4 weeks, 8 weeks, 3 months post intervention
Secondary	Metabolomic analysis of serum samples	Full metabolic profiling of serum samples will be used to assess changes to metabolic activity of participants.	4 weeks, 8 weeks, 3 months post intervention
Secondary	Faecal microbiome analysis	Sequences of ribosomal RNA (rRNA) in participant faecal samples will be measured to assess changes in the numbers or proportions of bacterial genera and species/strains.	4 weeks, 8 weeks, 3 months post intervention
Secondary	Incidence of self-reported seasonal cold, coronavirus and influenza-like illness.	A daily online form will be completed by participants to log any seasonal cold, coronavirus and influenza-like illness.	4 weeks, 8 weeks, 3 months post intervention
Secondary	Duration of self-reported illness.	A daily online form will be completed by participants to log any self-reported illness.	4 weeks, 8 weeks, 3 months post intervention
Secondary	Severity of self-reported illness.	A daily online form will be completed by participants to log any self-reported illness.	4 weeks, 8 weeks, 3 months post intervention
Secondary	Self-reported medication use.	A daily online form will be completed by participants to log any medication use.	4 weeks, 8 weeks, 3 months post intervention