Clinical trial NCT06827873: Effect of Oral Supplements for Influenza Vaccine Response
Official title: Effect of Oral Supplement Intervention on Influenza Vaccine Efficacy: a Randomized Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Influenza Vaccine Response
Keywords: Vaccine Efficacy
Elderly Immunity
Fatty Acid Supplementation
Gut Microbiota
Randomized Controlled Trial
Lead sponsor: Tsinghua University
Sponsor class: OTHER
Collaborators: name: Second Affiliated Hospital of Bengbu Medical College
First posted: 2025-02-14
Enrollment: 45
Sex: ALL
Minimum age (years): 60
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Forty-five adults aged 60-70 years are randomly assigned in equal numbers (n=15 per group) to three parallel groups: two intervention groups receiving different supplements(arachidonic acid and TUDCA) and one control group receiving placebo. The intervention period lasts 25 days, from Day 0 to Day 24. Triple-blinding is implemented to ensure that both participants and investigators are unaware of group assignments.
Primary purpose: PREVENTION

Brief summary: The aim of this clinical trial is to explore the efficacy of fatty acid and bile acid based supplements on enhancing influenza vaccine immune response in adults aged 60-70 years. The objectives of this study are:

1. To explore the efficacy of fatty acid and bile acid based supplements on enhancing flu vaccine immune response.
2. To evaluate the safety of fatty acid and bile acid use in elders.
3. To explore the potential role of microbiota in regulating immune response.

This study will conduct a randomized clinical trial to compare the efficacy of fatty acid / bile acid (Tauro Ursodesoxy Cholic Acid, TUDCA)supplements on enhancing vaccine immune response. The antibody's titer and safety indicators after influenza vaccination will be evaluated. Study process are:

1. Participants will be required to intake the assigned supplement or placebo daily for 25 days;
2. Receive a influenza vaccine on day 4;
3. Provide blood samples three times and stool samples twice at base line and endpoint respectively;
4. The antibody's titer and safety indicators will be analyzed and compared among groups.

This study aims to establish a theoretical foundation for utilizing nutritional strategies to enhance vaccine-induced immune responses and to provide a scientific framework for developing oral vaccine boosters.

Detailed description: Influenza virus infection presents a significant global health challenge, particularly threatening the elderly population due to immunosenescence. The immune response to influenza vaccination involves a complex series of events: after vaccination, hemagglutination inhibition antibody titers peak around day 14, accompanied by the production of neutralizing antibodies and other specific antibodies. This immune response gradually stabilizes to a post-response baseline level as immune memory establishes.

The age-related decline in immune function manifests through multiple mechanisms,including: reduced production of naive T cells; decreased diversity of T cell repertoire; compromised B cell function, altered cytokine production profiles which all diminished vaccine response efficacy.

Recent advances in immunometabolism have revealed the crucial role of specific fatty acids in immune system modulation. Our preliminary explorations found that，short-term Arachidonic Acid（AA）intervention could significantly reduce the time required for antibody production and enhance its levels following rabies vaccination. We also noticed that the serum Tauro Ursodesoxy Cholic Acid (TUDCA) was elevated in the intervention group. However, the related mechanism is still not clear.

The theoretical framework integrates nutritional immunology with classical vaccinology, focusing on the metabolic interaction between dietary fatty acids and immune cell function. This approach is particularly relevant for the elderly population, where reduced vaccine responsiveness due to immunosenescence presents a significant challenge in achieving optimal vaccine protection.

Eligibility criteria: Inclusion Criteria:

1. Age 60-70 years old
2. Body Mass Index (BMI) 18.5-26.9 kg/m²
3. No influenza vaccination in the past year
4. Able to understand and sign the informed consent form, and capable of completing the full follow-up process

Exclusion Criteria:

1. Severe lipid metabolism disorders
2. Use of lipid-lowering medications, weight loss drugs, or insulin within the past three months
3. Vaccination with other vaccines within the past three months
4. Use of probiotics or prebiotics within the past three months
5. Use of steroids, immunosuppressants, or other hormonal medications within the past year
6. Immunodeficiency diseases
7. Severe vaccine allergy history
8. Liver or kidney metabolic disorders
9. Occurrence of fever, common cold, severe diarrhea, or other diseases within the past month
10. Poorly controlled chronic diseases (such as blood pressure, blood sugar)
11. Intake of influenza antiviral drugs within the past two weeks
12. Cognitive function impairment
13. Planning to undergo surgery in the near future

Primary outcomes:
measure: Specific Antibody Levels and Neutralizing Antibody Responses to Influenza Vaccine
timeFrame: Day 13 and Day 24
Secondary outcomes:
measure: Changes in Inflammatory Markers
timeFrame: Day 0 and Day 24
measure: Gut Microbiota Composition Changes
timeFrame: Day 0 and Day 24
measure: Metabolomics Analysis
timeFrame: Day 0, Day 13 and Day 24
Other outcomes:
measure: Safety Assessment
timeFrame: Throughout the entire study period (Day 0-Day 24)
measure: Dietary Intake Assessment
timeFrame: Day 0 and Day 24
measure: Coagulation Function and Thrombosis Risk Assessment
timeFrame: Day 0 and Day 24
Locations:
city: Beijing
country: China
facility: Tsinghua University
state: Beijing
Study officials:
References:
citation: Sainz T, Casas I, Gonzalez-Esguevillas M, Escosa-Garcia L, Munoz-Fernandez MA, Prieto L, Gosalbes MJ, Jimenez-Hernandez N, Ramos JT, Navarro ML, Mellado MJ, Serrano-Villar S, Calvo C. Nutritional Supplementation to Increase Influenza Vaccine Response in Children Living With HIV: A Pilot Clinical Trial. Front Pediatr. 2022 Jul 19;10:919753. doi: 10.3389/fped.2022.919753. eCollection 2022.
citation: D'Onofrio V, Porrez S, Jacobs B, Alhatemi A, De Boever F, Waerlop G, Michels E, Vanni F, Manenti A, Leroux-Roels G, Platenburg PP, Hilgers L, Leroux-Roels I. Safety and Immunogenicity of a Carbohydrate Fatty Acid Monosulphate Ester Adjuvant Combined with a Low-Dose Quadrivalent Split-Virion Inactivated Influenza Vaccine: A Randomised, Observer-Blind, Active-Controlled, First-in-Human, Phase 1 Study. Vaccines (Basel). 2024 Sep 10;12(9):1036. doi: 10.3390/vaccines12091036.
citation: Chou CH, Mohanty S, Kang HA, Kong L, Avila-Pacheco J, Joshi SR, Ueda I, Devine L, Raddassi K, Pierce K, Jeanfavre S, Bullock K, Meng H, Clish C, Santori FR, Shaw AC, Xavier RJ. Metabolomic and transcriptomic signatures of influenza vaccine response in healthy young and older adults. Aging Cell. 2022 Sep;21(9):e13682. doi: 10.1111/acel.13682. Epub 2022 Aug 23.