The Role of the Intestinal Microbiome in Enteric and Systemic Vaccine Immune Responses

NCT02538211 | Completed

• 1 other identifier: NL 52510.018.15
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Rotavirus Infections; Intestinal Bacteria Flora Disturbance; Reaction - Vaccine Nos; Tetanus; Streptococcal Pneumonia

Outcome Measures

Primary Outcomes (1)

• Height of serum anti-rotavirus Immunoglobulin A (IgA) response

  Geometric Mean Concentration (GMC)

  28 days post-vaccination

Secondary Outcomes (6)

• Time to positivity for serum anti-rotavirus Immunoglobulin A (IgA) and G (IgG) response

  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

Study Arms (3)

Control

PLACEBO COMPARATOR

Control group - subjects will receive no antibiotics followed by Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine

Biological: Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine

Broad-spectrum antibiotics

ACTIVE COMPARATOR

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

Narrow-spectrum antibiotics

ACTIVE COMPARATOR

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

Interventions

Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine BIOLOGICAL

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.

Also known as: RotarixTM, Pneumo 23

Broad-spectrum antibiotics; Control; Narrow-spectrum antibiotics

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• Centers for Disease Control and Prevention: collaborator
• Wageningen University and Research: collaborator

Study Sites (1)

Academic Medical Center

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

MeSH Terms

Conditions

Rotavirus Infections; Tetanus; Pneumonia

Interventions

Rotavirus Vaccines; Tetanus Toxoid; Pneumococcal Vaccines

Condition Hierarchy (Ancestors)

Reoviridae Infections; RNA Virus Infections; Virus Diseases; Infections; Clostridium Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Toxoids; Streptococcal Vaccines; Bacterial Vaccines

Study Officials

• Willem J. Wiersinga, MD, PhD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: August 27, 2015
• First Posted: September 2, 2015
• Study Start: September 1, 2015
• Primary Completion: January 1, 2017
• Study Completion: February 1, 2017
• Last Updated: July 25, 2017

Record last verified: 2017-07

Locations

NL (1)