Clinical trial NCT03656198: Non-specific Effects of Rabies Vaccine
Official title: Non-specific Effects of Rabies Vaccine on the Incidence of Common Infectious Disease Episodes: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Influenza-like Illness
Upper Respiratory Disease
Diarrhea
Fever
Keywords: Non-Specific Effects of Vaccines
Heterologous Immunity
Rabies
Patient Reported Outcome Measures
Lead sponsor: Ross University School of Veterinary Medicine
Sponsor class: OTHER
Collaborators: name: Serum Institute of India Pvt. Ltd.
First posted: 2018-09-04
Enrollment: 546
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The trial design is a single-site, two-arm, parallel-group, participant-blinded, randomized, placebo-controlled, two-sided comparative study, with an internal pilot study for blinded sample size re-estimation. Allocation to study arm will be by block randomization stratified by sex within cohort (semester) with a 1:1 allocation ratio.
Primary purpose: PREVENTION

Brief summary: Vaccines work by stimulating the body to produce a high-quality, rapid and specific immune response upon exposure to infection by a particular disease-causing microorganism - the microorganism targeted by the vaccine. Evidence is emerging that some vaccines may have additional 'non-specific effects' (NSEs); that is, effects on the immune system beyond the direct protection against the diseases for which the vaccines were developed. It has been proposed that rabies vaccine has protective NSEs in people and animals, with receipt of rabies vaccine in children associated with a reduced risk of meningitis and cerebral malaria in one study, and a history of rabies vaccination in free-roaming dogs associated with increased survival rates in another study. Studies in mice have shown that prior rabies vaccination protects against bacterial sepsis. The biological mechanism of action of any such NSE of rabies vaccine is unknown. Other vaccines with reported protective NSEs (e.g. bacillus Calmette-Guerin vaccine against tuberculosis, a disease caused by Mycobacterium tuberculosis) have been show to reprogram the immune system, leading to enhanced protection against infection with disease-causing microorganisms unrelated to M. tuberculosis.

In this study, we will test the hypothesis that rabies vaccine has non-specific protective effects against common infectious disease (CID) syndromes (upper respiratory illness, diarrhea and fever) in a population of veterinary students. We will randomly assign previously-unvaccinated students who volunteer for the study to receive a primary course of three injections of rabies vaccine (experimental group) or an identical course of three injections of sterile water (control group). Participants will not know to which group they have been assigned. We will ask all participants to report episodes of illness through an online survey each week for 26 weeks, and will also record all clinically- and laboratory-confirmed cases of illness with CID syndromes. We hypothesize that rates of self-reported new episodes of CID illness over 26 weeks will be at least 25% lower in the experimental group, relative to the control group.


Eligibility criteria: Inclusion Criteria:

A student registered at RUSVM, and in the Veterinary Preparatory (VP) program or the 1st or 5th semester of the Doctor of Veterinary Medicine (DVM) program

Exclusion Criteria:

A student registered at RUSVM and in the VP program or the 1st or 5th semester of the DVM program will be excluded from the study if s/he:

1. has previously received a dose of rabies vaccine, or
2. is intending to undertake activities during the course of participation in the study that would increase their risk category of rabies exposure above that of the U.S. population at large, as defined by the Advisory Committee on Immunization Practices (ACIP) for human rabies prevention, or
3. does not provide informed consent for participation, or
4. enrolls in the study but does not present for the first injection within the first 12 weeks of the semester (up to and including Week 12), or
5. has a contraindication to rabies vaccine as described in the Rabivax-S package insert

Primary outcomes:
measure: Number of self-reported new episodes of acute common infectious disease (CID), defined as any of the following: upper respiratory illness (URI) or influenza-like illness (ILI) or diarrhea (DIA) or undifferentiated febrile illness (UFI)
timeFrame: Weekly self-reporting of occurrence or non-occurrence of episodes of CID for a maximum of 26 weeks, starting one week after allocation
Secondary outcomes:
measure: Number of self-reported new episodes of respiratory illness (URI or ILI), DIA and UFI
timeFrame: Weekly self-reporting of occurrence or non-occurrence of episodes of respiratory illness, DIA and UFI for a maximum of 26 weeks, starting one week after allocation
measure: Number of self-reported new weekly episodes of URI
timeFrame: Weekly self-reporting of occurrence or non-occurrence of episodes of URI for a maximum of 26 weeks, starting one week after allocation
measure: Number of self-reported new weekly episodes of ILI
timeFrame: Weekly self-reporting of occurrence or non-occurrence of episodes of ILI for a maximum of 26 weeks, starting one week after allocation
measure: Number of self-reported new weekly episodes of DIA
timeFrame: Weekly self-reporting of occurrence or non-occurrence of episodes of DIA for a maximum of 26 weeks, starting one week after allocation
measure: Number of self-reported new weekly episodes of UFI
timeFrame: Weekly self-reporting of occurrence or non-occurrence of episodes of UFI for a maximum of 26 weeks, starting one week after allocation
measure: Number of clinically-confirmed episodes of CID syndromes
timeFrame: 27 weeks after allocation
measure: Number of laboratory-confirmed episodes of CID syndromes
timeFrame: 27 weeks after allocation
Other outcomes:
Locations:
city: Basseterre
country: Saint Kitts and Nevis
facility: Ross University School of Veterinary Medicine
Study officials:
affiliation: Ross University School of Veterinary Medicine
name: Darryn Knobel, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Odita CI, Conan A, Smith-Antony M, Battice J, England S, Barry D, Gessner BD, Knobel DL. Non-specific effects of rabies vaccine on the incidence of self-reported common infectious disease episodes: A randomized controlled trial. Vaccine. 2022 Mar 8;40(11):1617-1623. doi: 10.1016/j.vaccine.2021.06.007. Epub 2021 Jun 11.
citation: Knobel D, Odita CI, Conan A, Barry D, Smith-Anthony M, Battice J, England S, Gessner BD. Non-specific effects of rabies vaccine on the incidence of common infectious disease episodes: study protocol for a randomized controlled trial. Trials. 2020 Jun 16;21(1):534. doi: 10.1186/s13063-020-04467-z.