Non-specific Effects of Rabies Vaccine
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|ClinicalTrials.gov Identifier: NCT03656198|
Recruitment Status : Enrolling by invitation
First Posted : September 3, 2018
Last Update Posted : September 5, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Influenza-like Illness Upper Respiratory Disease Diarrhea Fever||Biological: Rabivax-S Drug: Sterile Water Injection||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||430 participants|
|Intervention Model:||Parallel Assignment|
|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.|
|Masking Description:||Participants will be blinded to their study arm allocation. The intervention procedure will be identical for both arms (intramuscular injections at Student Health Services on days 0, 7 and 21). Participants allocated to the control group will receive an intramuscular injection of sterile water for injection using identical syringes and needles as for the vaccine group. The injection will be prepared in a separate room to maintain participant blinding.|
|Official Title:||Non-specific Effects of Rabies Vaccine on the Incidence of Common Infectious Disease Episodes: a Randomized Controlled Trial|
|Actual Study Start Date :||August 29, 2018|
|Estimated Primary Completion Date :||July 2020|
|Estimated Study Completion Date :||July 2020|
Experimental: Vaccine group
Three dose primary course of Rabivax-S. Dosing and administration of the vaccine (Rabivax-S) will be according to the package insert, following the schedule for pre-exposure prophylaxis via the intramuscular route; that is, 1 mL by intramuscular injection in the deltoid area of the arm on Day 0, Day 7 and Day 21.
Rabivax-S is a lyophilized vaccine manufactured by Serum Institute of India Pvt. Ltd. containing inactivated purified rabies antigen (Pitman Moore, PM3218 as virus strain) produced using Vero ATCC CCL 81 cells. The diluent (sterile water for injection) is provided in a separate 1 mL ampoule. After reconstitution, a single dose of 1 mL contains an inactivated, purified rabies antigen (not less than 2.5 IU), glycine (40 mg), sucrose (40 mg) and human serum albumin (25% 10 mg).
Placebo Comparator: Control group
The intervention (placebo) in the control group is at least one dose (1 mL by intramuscular injection) of a three dose primary course (on days 0, 7 and 21) of vaccine diluent (sterile water for injection).
Drug: Sterile Water Injection
The vaccine diluent (sterile water for injection) is provided in a separate 1 mL ampoule.
- 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) [ Time Frame: Weekly self-reporting of occurrence or non-occurrence of episodes of CID for a maximum of 26 weeks, starting one week after allocation ]
URI is defined as (two or more of the following: runny or blocked nose/sneezing/sore throat/cough) and (absence of itchy or watery eyes).
ILI is defined as [fever (feeling feverish, or an axillary, oral or otic temperature of 100°F or higher)] and (cough or sore throat).
DIA is defined as three or more loose stools within a 24-hour period.
UFI is defined as [fever (feeling feverish, or an axillary, oral or otic temperature of 100°F or higher)] and (not meeting the case definition of URI, ILI or DIA).
To be defined as a new episode, illness must be preceded by at least one week without any CID.
- Number of self-reported new episodes of respiratory illness (URI or ILI), DIA and UFI [ Time Frame: 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 ]
- Number of self-reported new weekly episodes of URI [ Time Frame: Weekly self-reporting of occurrence or non-occurrence of episodes of URI for a maximum of 26 weeks, starting one week after allocation ]To be defined as a new episode, illness must be preceded by at least one week without any URI.
- Number of self-reported new weekly episodes of ILI [ Time Frame: Weekly self-reporting of occurrence or non-occurrence of episodes of ILI for a maximum of 26 weeks, starting one week after allocation ]To be defined as a new episode, illness must be preceded by at least one week without any ILI.
- Number of self-reported new weekly episodes of DIA [ Time Frame: Weekly self-reporting of occurrence or non-occurrence of episodes of DIA for a maximum of 26 weeks, starting one week after allocation ]To be defined as a new episode, illness must be preceded by at least one week without any DIA.
- Number of self-reported new weekly episodes of UFI [ Time Frame: Weekly self-reporting of occurrence or non-occurrence of episodes of UFI for a maximum of 26 weeks, starting one week after allocation ]To be defined as a new episode, illness must be preceded by at least one week without any UFI.
- Number of clinically-confirmed episodes of CID syndromes [ Time Frame: 27 weeks after allocation ]Clinically-confirmed episodes of CID syndromes, defined as an episode resulting in a visit to the RUSVM Student Health Services with a recorded ICD10 of J00 (acute nasopharyngitis); J11 (influenza due to unidentified influenza virus); R19.7 (diarrhea) or R50.9 (fever, unspecified).
- Number of laboratory-confirmed episodes of CID syndromes [ Time Frame: 27 weeks after allocation ]Laboratory-confirmed episodes of CID syndromes, defined as clinically-confirmed episodes with laboratory diagnosis of influenza virus, respiratory syncytial virus or metapneumovirus (URI/ILI episodes) or rotavirus or norovirus (DIA episodes)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03656198
|Saint Kitts and Nevis|
|Ross University School of Veterinary Medicine|
|Basseterre, Saint Kitts and Nevis|
|Principal Investigator:||Darryn Knobel, PhD||Ross University School of Veterinary Medicine|