Clinical trial NCT02538211: The Role of the Intestinal Microbiome in Enteric and Systemic Vaccine Immune Responses
Official title: The Role of the Intestinal Microbiome in Enteric and Systemic Vaccine Immune Responses
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Rotavirus Infections
Intestinal Bacteria Flora Disturbance
Reaction - Vaccine Nos
Tetanus
Streptococcal Pneumonia
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: Centers for Disease Control and Prevention
name: Wageningen University and Research
First posted: 2015-09-02
Enrollment: 63
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate if the intestinal microbiota influences rotavirus vaccine immune responses in healthy adult volunteers.

Detailed description: This study will alter the intestinal microbiota in healthy adults using antibiotics and subsequently measure immune reactions to the rotavirus vaccine (Rotarix), the tetanus vaccine and the pneumococcal vaccine (Pneumo23).

Eligibility criteria: Inclusion 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 -98). 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:

* 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
* Subjects with a history of any type of malignancy
* Subject with a history of thrombocytopenia or bleeding disorder
* 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

Primary outcomes:
measure: Height of serum anti-rotavirus Immunoglobulin A (IgA) response
timeFrame: 28 days post-vaccination
Secondary outcomes:
measure: Time to positivity for serum anti-rotavirus Immunoglobulin A (IgA) and G (IgG) response
timeFrame: day 0 through day 28 post vaccination
measure: Change in pre and post-vaccination anti-rotavirus (anti-RV) serum neutralizing antibodies measured by Geometric Mean Concentration (GMC)
timeFrame: 28 days post-vaccination
measure: Change in pre and post-vaccination anti-RV serum IgG response measured by Geometric Mean Concentration (GMC)
timeFrame: day 0 through day 28 post vaccination
measure: Change in serum tetanus toxoid IgG response, measured as pre and post vaccination titer (international units/mL) ratio
timeFrame: day 0 through day 28 post vaccination
measure: Change in serum pneumococcal poly-saccharide-specific IgG for all vaccine strains , measure in pre and post vaccination titer (micrograms/mL) ratio
timeFrame: day 0 through day 28 post vaccination
measure: Composition of the fecal micro biome before and after antibiotics and between groups measured by the HITChip and bacterial 16S rRNA sequencing
timeFrame: day -9 and day 0 pre vaccination
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
state: Noord-Holland
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Willem J. Wiersinga, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: