The Role of Fatty Acids in Vaccine Efficacy

The Role of Fatty Acids in Vaccine Efficacy: A Randomized Controlled Clinical Trial

This study intends to use a randomized controlled trial design to vaccinate all participants against rabies and perform ARA interventions during vaccination to test the efficacy, safety, and intestinal flora of each group after immunization.

Study Overview

• Status: Completed
• Conditions: Rabies Vaccination Reaction
• Intervention / Treatment: Dietary supplement: Sunflower oil; Biological: Rabies Vaccine (Vero Cell) for Human Use; Dietary supplement: Arachidonic acid

Detailed Description

Rabies is an acute zoonotic infectious disease caused by central nervous system invasion by rabies virus. At present, there is still a lack of effective treatment, and once clinical symptoms appear, it is almost 100% fatal. Rabies vaccination within 24 hours of exposure may reduce the incidence of rabies. Pre-exposure prophylaxis is also effective, and the current recommended pre-exposure vaccination program in China is 0 days, 7th day, 21st days.

The health of the human body is inseparable from various nutrients. There are studies suggesting that arachidonic acid(ARA) has an immunomodulatory effect, but there is limited evidence for its effect on vaccines. Therefore, this study will explore the effects of nutritional supplements on the effectiveness of rabies vaccination.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100084
      • Tsinghua University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 1）18-45 years old;
• 2）BMI 18.5-24.9 kg/m2;
• 3）Have not received rabies vaccination.

Exclusion Criteria:

• 1) Those who have severe disorders of abnormal lipid metabolism;
• 2) Those who have used lipid-lowering drugs, weight loss drugs, and insulin drugs in the past three months;
• 3) Those who have received other vaccines in the past three months;
• 4) Those who have used probiotics or prebiotics in the past three months;
• 5) Those who have used steroids and immunosuppressants, other hormonal drugs in the past year;
• 6) Those with immunodeficiency diseases;
• 7) Those with a history of severe vaccine allergies;
• 8) Those who have disorders of liver and kidney metabolism;
• 9) Those who have had fever, cold, severe diarrhea and other diseases in the past month.
• 10) Smokers in the last year.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo group; Sunflower oil capsules	Dietary supplement: Sunflower oil; The placebo group and D6 ARA group will receive sunflower oil capsules from the third day of the study. D6 ARA group will stop receiving sunflower oil capsules from the fifth day of the study.; Biological: Rabies Vaccine (Vero Cell) for Human Use; Every participant will receive three doses of rabies vaccination.
Experimental: D3 ARA group; ARA capsules	Biological: Rabies Vaccine (Vero Cell) for Human Use; Every participant will receive three doses of rabies vaccination.; Dietary supplement: Arachidonic acid; D3 ARA group will receive ARA capsules from the third day of the study. D6 ARA group will receive ARA capsules from the sixth day of the study
Experimental: D6 ARA group; Sunflower oil capsules and ARA capsules	Dietary supplement: Sunflower oil; The placebo group and D6 ARA group will receive sunflower oil capsules from the third day of the study. D6 ARA group will stop receiving sunflower oil capsules from the fifth day of the study.; Biological: Rabies Vaccine (Vero Cell) for Human Use; Every participant will receive three doses of rabies vaccination.; Dietary supplement: Arachidonic acid; D3 ARA group will receive ARA capsules from the third day of the study. D6 ARA group will receive ARA capsules from the sixth day of the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of rabies virus antibody titers	specific antibody titers	Day 6, 13, 16, 19, 26 of the study
Changes of neutralizing antibody titers	To test the ability of binding to rabies virus	Day 6, 13, 16, 19, 26 of the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serum blood fatty acid profiles	to test the change of fatty acid profiles after intervention	Day 6, 13, 16，19 of the study
C-reactive protein	to test the potential C-reactive protein changes triggered by ARA supplementation	Day 6, 13, 16 and 19 of the study
Routine analysis of intestinal flora: alpha diversity	The alpha diversity of microbiota in feces samples will be examined to explore the potential gut-immune response caused by intervention.	Day 3 and day 19 of the study
Routine analysis of intestinal flora: beta diversity	The beta diversity of microbiota in feces samples will be examined to explore the potential gut-immune response caused by the intervention.	Day 3 and day 19 of the study
Routine analysis of intestinal flora: species abundance histogram	The species abundance histogram of microbiota in feces samples will be examined to explore the potential gut-immune response caused by the intervention.	Day 3 and day 19 of the study
Routine analysis of intestinal flora: Lefse	The Lefse of microbiota in feces samples will be conducted to explore the potential gut-immune response caused by the intervention.	Day 3 and day 19 of the study
Routine analysis of intestinal flora: PLS-DA	The PLS-DA of microbiota in feces samples will be conducted to explore the potential gut-immune response caused by the intervention.	Day 3 and day 19 of the study
Routine analysis of intestinal flora: KEGG pathway	The KEGG pathway microbiota in feces samples will be analyzed to explore the potential gut-immune response caused by the intervention.	Day 3 and day 19 of the study
Routine analysis of intestinal flora: differential KO expression	The differential KO expression microbiota in feces samples will be analyzed to explore the potential gut-immune response caused by the intervention.	Day 3 and day 19 of the study
Macrogenomic sequencing difference of intestinal flora	The macrogenomic sequencing analysis of microbiota in feces samples will be conducted to explore the potential gut-immune response caused by the intervention.	Day 3 and day 19 of the study
Fecal fatty acid content	The fatty acid content in feces samples will be examined to explore the change of fatty acid intake caused by the intervention.	Day 3 and day 19 of the study

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events by ARA	To examine the safety of using ARA, including allergy, gastrointestinal discomfort and others.	Day 3 to day 30 of the trial.
Serum triglyceride levels	To examine the changes of blood lipids in blood after intervention and evaluate the intervention safety. The spacific measurements include: Triglycerides (TG), high-density lipoprotein cholesterol (HDL-CHO), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC).	Days 3 and day 19 of the study.
Blood count: red blood cells	To evaluate the intervention safety.	tested on day 3 and day 19 of the trial.
Blood count: white blood cells	To evaluate the intervention safety.	tested on day 3 and day 19 of the trial.
Blood count: hemoglobin	To evaluate the intervention safety.	tested on day 3 and day 19 of the trial.
Blood count: hematocrit	To evaluate the intervention safety.	tested on day 3 and day 19 of the trial.
Blood count: platelets	To evaluate the intervention safety.	tested on day 3 and day 19 of the trial.
Anxiety	Evaluated with General Anxiety Disorder-7 items. The scores are between 0 to 21, higher scores mean a worse outcome.	tested on day 13 of the trial.
Depression	Evaluated with Patient Health Questionaire-9 items. The scores are between 0 to 27, higher scores mean a worse outcome.	tested on day 13 of the trial.

Collaborators and Investigators

• Sponsor: Tsinghua University
• Investigators: Study Chair: Ai Zhao, Doctor, Tsinghua University

Publications and helpful links

General Publications

• Shen T, Welburn SC, Sun L, Yang GJ. Progress towards dog-mediated rabies elimination in PR China: a scoping review. Infect Dis Poverty. 2023 Apr 6;12(1):30. doi: 10.1186/s40249-023-01082-3.

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2023
• Primary Completion (Actual): July 30, 2023
• Study Completion (Actual): July 30, 2023

Study Registration Dates

• First Submitted: June 8, 2023
• First Submitted That Met QC Criteria: August 8, 2023
• First Posted (Actual): August 14, 2023

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 8, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: efficacy; Arachidonic acid; Rabies Vaccination
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Mononegavirales Infections; Rhabdoviridae Infections; Rabies
• Other Study ID Numbers: 20220081

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No