The Role of the Intestinal Microbiome in Enteric and Systemic Vaccine Immune Responses (Rota-biome)

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

Study Overview

• Status: Completed
• Conditions: Tetanus; Rotavirus Infections; Reaction - Vaccine Nos; Intestinal Bacteria Flora Disturbance; Streptococcal Pneumonia
• Intervention / Treatment: Biological: Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine

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).

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1105 AZ
      • Academic Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Control; Control group - subjects will receive no antibiotics followed by Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine	Biological: Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine; All subjects will be given an oral dose of the rotavirus vaccine, RotarixTM, and intramuscular injections of the Tetanus vaccine and Pneumococcal vaccine, Pneumo 23.; Other Names: RotarixTM, Pneumo 23
ACTIVE_COMPARATOR: Broad-spectrum antibiotics; Subjects will receive 7 days of pre-treatment (days -9 to -3) with: Ciprofloxacin 500mg 2dd1; Vancomycin 250mg 3dd2; Metronidazole 500mg 3dd1 followed by Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine	Biological: Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine; All subjects will be given an oral dose of the rotavirus vaccine, RotarixTM, and intramuscular injections of the Tetanus vaccine and Pneumococcal vaccine, Pneumo 23.; Other Names: RotarixTM, Pneumo 23
ACTIVE_COMPARATOR: Narrow-spectrum antibiotics; Subjects will receive 7 days of pre-treatment (days -9 to -3) with: • Vancomycine 250mg 3dd2 followed by Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine	Biological: Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine; All subjects will be given an oral dose of the rotavirus vaccine, RotarixTM, and intramuscular injections of the Tetanus vaccine and Pneumococcal vaccine, Pneumo 23.; Other Names: RotarixTM, Pneumo 23

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Height of serum anti-rotavirus Immunoglobulin A (IgA) response	Geometric Mean Concentration (GMC)	28 days post-vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to positivity for serum anti-rotavirus Immunoglobulin A (IgA) and G (IgG) response	(days)	day 0 through day 28 post vaccination
Change in pre and post-vaccination anti-rotavirus (anti-RV) serum neutralizing antibodies measured by Geometric Mean Concentration (GMC)		28 days post-vaccination
Change in pre and post-vaccination anti-RV serum IgG response measured by Geometric Mean Concentration (GMC)		day 0 through day 28 post vaccination
Change in serum tetanus toxoid IgG response, measured as pre and post vaccination titer (international units/mL) ratio		day 0 through day 28 post vaccination
Change in serum pneumococcal poly-saccharide-specific IgG for all vaccine strains , measure in pre and post vaccination titer (micrograms/mL) ratio		day 0 through day 28 post vaccination
Composition of the fecal micro biome before and after antibiotics and between groups measured by the HITChip and bacterial 16S rRNA sequencing		day -9 and day 0 pre vaccination

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: Centers for Disease Control and Prevention; Wageningen University and Research
• Investigators: Principal Investigator: Willem J. Wiersinga, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2015
• Primary Completion (ACTUAL): January 1, 2017
• Study Completion (ACTUAL): February 1, 2017

Study Registration Dates

• First Submitted: August 27, 2015
• First Submitted That Met QC Criteria: September 1, 2015
• First Posted (ESTIMATE): September 2, 2015

Study Record Updates

• Last Update Posted (ACTUAL): July 25, 2017
• Last Update Submitted That Met QC Criteria: July 24, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumonia, Bacterial; Reoviridae Infections; Pneumococcal Infections; Pneumonia, Pneumococcal; Rotavirus Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: NL 52510.018.15