Primary Objective: to investigate the role of the gut microbiota in RVV immune response Secondary Objectives: To investigate the role of the gut microbiota in tetanus and pneumococcal vaccine immune responses
ID
Source
Brief title
Condition
- Other condition
- Gastrointestinal infections
- Viral infectious disorders
Synonym
Health condition
vaccin immunogeniciteit
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameters/endpoints: The main study endpoint is the 28-day post
vaccination anti-RV IgA serum response.
Secondary outcome
Secondary study parameters are the height, slope and time to positivity of the
post-vaccination anti-RV IgA, anti-pneumococcal antibodies and anti-tetanus
toxoid antibodies, and fecal rotavirus antigen shedding days 1-7 post rotavirus
vaccination. Differences in the composition and diversity of the intestinal
microbiota before and after antibiotic use and between groups. Isolation and
stimulation of peripheral blood mononuclear cells (PBMC) pre and post
vaccination with vaccines. Correlation between self-reported diet (4 day log)
and microbiome composition.
Background summary
Rationale: Rotavirus (RV) is the leading cause of diarrhea-related death in
children under five years of age, particularly in Africa and Asia. Rotavirus
vaccines (RVV) have the potential to dramatically reduce rotavirus morbidity
and mortality, however rotavirus vaccine efficacy is lowest in the poorest
countries with the highest child mortality rate.
We hypothesize that differences in gut microbiome colonization, composition and
diversity might be contributing to the diminished RVV efficacy observed in
developing countries. We propose evaluating the effects of intestinal
microbiota differences obtained through antibiotics on RVV immune responses.
To obtain a better mechanistic understanding of the relationship between the
intestinal microbiota and vaccine immune responses, this study also proposes
evaluating the effect of antibiotic microbiota manipulation on two well-studied
and classic systemic vaccines: the tetanus vaccine and the pneumococcal vaccine
(Pneumo23).
Study objective
Primary Objective: to investigate the role of the gut microbiota in RVV immune
response
Secondary Objectives: To investigate the role of the gut microbiota in tetanus
and pneumococcal vaccine immune responses
Study design
Study design: Randomized, controlled intervention study in adult human
volunteers
Intervention
Intervention:
Arm 1 (control): no antibiotic depletion then RotarixTM, Tetanus and
Pneumococcus vaccination;
Arm 2: broad-spectrum antibiotic depletion (ciprofloxacin, vancomyin,
metronidazole) then RotarixTM, Tetanus, and Pneumococcus vaccination;
Arm 3: Gram-positive depletion (oral vancomycin) then RotarixTM, Tetanus, and
Pneumococcus vaccination
Study burden and risks
Nature and extent of the burden and risks associated with participation,
benefit and group relatedness:
The burden of this study includes vaccination (one oral two intramuscular),
oral antibiotics, and 5 visits after the screening visit to the hospital,
spread out over 5 1/2 weeks. Intramuscular vaccinations can give local
irritation, pain, muscle soreness and aching.
Vaccination can give transient malaise and infrequently, fever.
Oral antibiotic use could lead to gastrointestinal symptoms and (rarely)
allergic reactions.
The results of this study might lead to interventions that could improve the
immunogenicity of rotavirus vaccine in developing countries, potentially
preventing hundreds of thousands of deaths due to rotavirus disease over the
next 15 years. It could also elucidate important immune mechanisms involved in
oral and systemic vaccination.
Meibergdreef 9 Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9 Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
* Healthy, as determined by a responsible physician, based on a medical evaluation including medical history, physical examination and laboratory tests carried out within 28 days prior to starting antibiotics (day -9). A subject with a clinical abnormality or laboratory parameter outside the reference range may be included if the investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures
* Male between 18 and 35 years of age, inclusive at the time of signing the informed consent
* Capable of giving written informed consent and able to comply with the requirements and restrictions listed in the informed consent form
* Normal defecation pattern (defined as *3x/ day and *3x/week)
Exclusion criteria
* Baseline anti-rotavirus immunglobluin A level greater than 20 IU/mL or equivalent geometric mean titer.
* Subject has had a major illness in the past 3 months or any significant chronic medical illness that the investigator would deem unfavorable for enrollment, including inflammatory diseases.
* Subject with any history of immunodeficiency
Subject with a history of thrombocytopenia or bleeding disorder
* Subjects with a history of any type of malignancy
* Subject has a past or current gastrointestinal disease which may influence the gut microbiota
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
* History of alcoholism and/or drinking more than an average of 5 units of alcohol per day
* The subject has received an investigational product within three months of day 0 of the current study
* Use of prescription or non-prescription drugs and herbal and dietary supplements within 6 months unless in the opinion of the investigator the medication will not interfere with the study procedures or compromise subject safety
* Recent (< 12 months) use of antibiotics (any kind, except for dermal antibiotics)
* Known allergy to antibiotics (any kind)
* Allergy to any vaccine components (any kind, including allergy to egg white, thiomersal and phenol) or past adverse reaction of any kind to a tetanus or pneumococcal vaccination
* Subject has difficulty in donating blood or accessibility of a vein in left or right arm
* Subject has donated more than 350 mL of blood in last 3 months
* Difficulty swallowing pills
* Body mass index >28 kg/m2
* Any other issue that, in the opinion of the investigator, could be harmful to the subject or compromise interpretation of the data
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL52510.018.15 |