Immunologic Responses to a Live Attenuated Oral Cholera Vaccine

Cholera Clinical Trial

Official title:

Immunologic Responses to a Live Attenuated Oral Cholera Vaccine

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03251495
• Other study ID #: IRB00097012
• Secondary ID: R01AI137127
• Status: Recruiting
• Phase: Phase 2
• Start date: August 29, 2017
• Est. completion date: June 30, 2025

Study information

• Verified date: June 2023
• Source: Emory University
• Contact: Nadine Rouphael, MD
• Phone: 404-712-1370
• Email: nroupha[@]emory.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to evaluate the antibody response to the cholera vaccine, Vaxchora®, in healthy subjects.

Investigators also seek to evaluate additional markers of the adaptive immune response including plasmablasts, activated B cells, memory B cells, and T cell responses in healthy subjects receiving cholera vaccine, produce monoclonal antibodies against cholera, and evaluate the safety and reactogenicity in healthy subjects receiving cholera vaccine.

Description:

Cholera is a life-threatening illness that causes diarrhea. Cholera is caused by eating or drinking the Vibrio cholera bacteria. Each year, there are about 1.3 to 4.0 million cases of cholera worldwide, resulting in 21,000 to 143,000 deaths. The bacteria is spread through water or food that has stool in it. Up to 50 countries with limited access to clean water are more likely to have outbreaks. In the United States most cases are linked to travel to these countries; however, there are 10-15 cases acquired in the United States each year because of undercooked seafood. Cholera spreads very easily. Illness from Cholera can vary from no symptoms to severe watery diarrhea that can cause death by dehydration in a healthy person within hours.

Vaxchora is a live attenuated cholera vaccine that protects against some cholera strains. It has been approved by the FDA since June 2016. Since October, 2016, this vaccine has been recommended for certain travelers 18 through 64 years of age going to cholera-affected areas. The purpose of this study is to look at the immune responses to the FDA approved cholera vaccine (Vaxchora®).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 49 Years

Eligibility

Inclusion Criteria:

• Capable of informed consent and provision of written informed consent before any study procedures

• Capable of attending all study visits according to the study schedule

• Are in good health, as determined by medical history and targeted physical exam related to this history

• Female subjects of childbearing age must have a negative urine pregnancy test before study vaccination, and must use two forms of contraception to avoid pregnancy within one month of Vaxchora administration

Exclusion Criteria:

• Have an acute illness within 72 hours before vaccination

• Have any acute or chronic medical condition that, in the opinion of the principal investigator, would make vaccination unsafe or interfere with the evaluation of immune response to study vaccination

• Have a suppressed immune system as a result of illness, immunosuppressive medication, chemotherapy, or radiation therapy within 3 years prior to study vaccination

• Have taken oral or parenteral corticosteroids of any dose within 30 days before study vaccination

• Reside with individuals under the age of 2 or with an immunocompromised individuals

• Have a known history of autoimmune disease

• Have a history of Guillain-Barre Syndrome

• Have plans to receive any vaccine from 28 days prior to study vaccination until Day 29

• Has previously received a cholera vaccine or have a known history of V. Cholerae.

• Have donated blood or blood products within 56 days before study vaccination, plan to donate blood at any time during the 56-day duration of subject study participation, or plan to donate blood within 56 days after the last blood draw

• Have known hypersensitivity or allergy to any component of the vaccine or history of anaphylaxis with a vaccine or vaccine component

• Have allergy to tetracycline and/or ciprofloxacin

• Are pregnant or breastfeeding or plan to within one month of vaccination

• Traveled to a cholera endemic area and had traveler's diarrhea in the previous 5 years

• Have abnormal stool pattern (fewer than 3 stools/ week or greater than 2 stools/ day) or regular use of laxatives in the last 6 months

• Have current or recent antibiotic use in the past 14 days

• Are healthcare workers who have direct contact with patients who are immunocompromised, have unstable medical conditions, or are under the age of 2

• Are childcare caregivers who have direct contact with children who are 2 years or younger.

• Are employed in the food industry

• Have received any vaccine within the previous 21 days

• History of bleeding disorders or current use of warfarin, aspirin, heparin, nonsteroidal anti-inflammatory drugs (NSAIDs) or other blood thinner/ anticoagulant medications in the past week for subjects undergoing intestinal biopsies.

• Use of benzodiazepines or narcotics for subjects undergoing intestinal biopsies 4 weeks prior to the procedure

• Any contraindications to endoscopy/concerns of the anesthesiologist for subjects who agree for esophagogastroduodenoscopy (EGD)/biopsies.

• BMI > 35 kg/m2

• Have a diagnosis of any small bowel disease. This includes but is not limited to inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, indeterminate colitis, or microscopic colitis), small bowel obstruction, celiac disease, h/o small bowel resection, small bowel lymphoma, Whipple's disease, primary Intestinal lymphangiectasis, abdominal radiation.

• Current medications for the treatment of Gastroesophageal reflux disease (GERD) or dyspepsia

• History of Helicobacter pylori (H. pylori) infection

Related Conditions & MeSH terms

• Cholera

Intervention

Drug:
• Vaxchora
Vaxchora is a live attenuated cholera vaccine that provides immunity against V. cholerae serogroup O1. Participants will receive one single oral dose of 100 mL.

Locations

Country	Name	City	State
United States	The Hope Clinic of Emory University	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Positive Responders	Antibody titers will be collected to assess the level of immune response to vaccination. A positive responder is defined as a participant with a titer above 40 at day 29, or that shows a four-fold increase over baseline.	Day 29
Secondary	Plasmablast Levels	Plasmablasts will be collected via blood draw and isolated and assessed for counts by the study team. A positive response is defined as a four-fold increase over the baseline measure.	Day 29
Secondary	Activated B Cell Levels	Activated B cells will be collected via blood draw and isolated and assessed for counts by the study team. A positive response is defined as a four-fold increase over the baseline measure.	Day 29
Secondary	Memory B-Cell Levels	Memory B-cells will be collected via blood draw and isolated and assessed for counts by the study team. A positive response is defined as a four-fold increase over the baseline measure.	Day 29
Secondary	Memory T-Cell Levels	T-cells will be collected via blood draw and isolated and assessed for counts by the study team. A positive response is defined as a four-fold increase over the baseline measure.	Day 29
Secondary	Number of Samples from which Monoclonal Antibodies Produced	The ability to isolate monoclonal antibodies will be assessed by study lab personnel.	Day 29
Secondary	Number of Adverse Events	The number of solicited and unsolicited adverse events will be collected.	Duration of Study (Up to 29 Days)
Secondary	Number of Serious Adverse Events	The number of serious adverse events will be collected.	Duration of Study (Up to 29 Days), Day 365