PTM202 and Modulation of Host Resistance to Diarrheagenic E. Coli

NCT ID: NCT03301103

Last Updated: 2018-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-07
• Study Completion Date: 2018-03-16

Brief Summary

The APA12/PANTER study is a parallel 3-weeks intervention study. Subjects will be randomly assigned to one of two treatment groups; placebo or PTM202 (n=36 per group). After an overnight fast, subjects will be orally infected with a live, but attenuated, diarrheagenic E. coli at study day 14. At various time points before and after diarrheagenic E. coli challenge an online diary will be kept to record information on stool consistency, frequency and severity of symptoms and stool samples will be collected to determine total fecal wet weight and percentage of fecal wet weight.

Detailed Description

The APA12/PANTER study is a randomized, double-blind, placebo-controlled, parallel intervention study of 3 weeks in 72 healthy adults. The study will include 2 arms; PTM202 and placebo. Subjects will be instructed to maintain their usual pattern of physical activity and their habitual food intake, but to standardize their dietary calcium intake. After an overnight fast, subjects will be orally infected with a live, but attenuated, diarrheagenic E. coli (strain E1392-75-2A; collection NIZO food research; dose 1E10 CFU (at study day 14).

At study day 14, 15 and 16 subjects will receive either placebo or PTM202, a dietary formula containing dried bovine colostrum and dried whole egg.

Before and after the diarrheagenic E. coli challenge an online diary will be kept to record information on stool consistency, frequency, severity of symptoms and mediation intake. At various time points before and after diarrheagenic E. coli challenge stool samples will be collected. The main study parameters are Stool consistency (Bristol Stool Scale reported by the subjects in the online diary, and Percentage of fecal wet weight (% determined by freeze-drying).

Secondary study parameters are: Stool frequency (Stools per day reported by the subjects in the online diary), Total fecal wet weight (fecal weight in g/day), and the incidence and severity of Gastro-intestinal symptoms (Gastro-intestinal Symptom Rating Scale reported by the subjects in the online diary).

Conditions

Traveler's Diarrhea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo

The placebo will consist of low-lactose isonitrogenous soy product, and will be matched in appearance and flavour to PTM202.

After an overnight fast, subjects will be orally infected with a live, but attenuated, diarrheagenic E. coli (strain E1392-75-2A; collection NIZO food research; dose 1E10 CFU (at study day 14).

Group Type: PLACEBO_COMPARATOR

E. coli strain E1392-75-2A

Intervention Type: BIOLOGICAL

After an overnight fast, subjects will be orally infected with a live, but attenuated, diarrheagenic E. coli (strain E1392-75-2A; collection NIZO food research; dose 1E10 CFU (at study day 14).

PTM202

PTM202 is a dry powder for reconstitution, comprised of a proprietary mixture of dried bovine colostrum and dried whole egg.

After an overnight fast, subjects will be orally infected with a live, but attenuated, diarrheagenic E. coli (strain E1392-75-2A; collection NIZO food research; dose 1E10 CFU (at study day 14).

Group Type: EXPERIMENTAL

E. coli strain E1392-75-2A

Intervention Type: BIOLOGICAL

After an overnight fast, subjects will be orally infected with a live, but attenuated, diarrheagenic E. coli (strain E1392-75-2A; collection NIZO food research; dose 1E10 CFU (at study day 14).

PTM202

Intervention Type: DEVICE

PTM202 is a dietary formula containing a proprietary mixture of dried bovine colostrum and dried whole egg.

Interventions

E. coli strain E1392-75-2A

After an overnight fast, subjects will be orally infected with a live, but attenuated, diarrheagenic E. coli (strain E1392-75-2A; collection NIZO food research; dose 1E10 CFU (at study day 14).

Intervention Type: BIOLOGICAL

PTM202

PTM202 is a dietary formula containing a proprietary mixture of dried bovine colostrum and dried whole egg.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Male;

2. Age between 18 and 55 years;

3. BMI ≥18 and ≤27 kg/m2;

4. Healthy as assessed by the NIZO food research medical questionnaire.

5. Ability to follow verbal and written instructions;

6. Availability of internet connection;

7. Signed informed consent;

8. Willing to accept disclosure of the financial benefit of participation in the study to the authorities concerned;

9. Willing to accept use of all encoded data, including publication, and the confidential use and storage of all data for at least 15 years;

10. Willing to comply with study procedures, including collection of stool samples;

11. Willingness to abstain from high calcium containing products;

12. Willingness to abstain from alcoholic beverages three days before, during and for four days after diarrheagenic E. coli challenge;

13. Willingness to abstain from antibiotics, norit, laxatives, nonsteroidal anti-inflammatory drugs (OTC), opiates, antacids, proton pump inhibitors, and antimotility agents (e.g., loperamide) on the three days before, during and for four days after diarrheagenic E. coli challenge.

14. Willingness to abstain from probiotics three days before, during and for four days after diarrheagenic E. coli challenge;

15. Willingness to give up blood donation starting 1 month prior to study start and during the entire study;

Exclusion Criteria

1. Any confirmed or suspected immunosuppressive or immunodeficient condition including human immunodeficiency virus infection (HIV);

2. Disease of the GI tract, liver, bile bladder, kidney, thyroid gland (self-reported);

3. Diarrheagenic E. coli strain (as used in the study) detected in fecal sample at screening;

4. Evidence of current excessive alcohol consumption or non-therapeutic drug (ab)use);

5. High titer serum antibodies against CFA-II diarrheagenic E. coli strain (as used in the study) at screening;

6. History of microbiologically confirmed ETEC or cholera infection in last 3 years;

7. Known allergy to the following antibiotics: ciprofloxacin, trimethoprim-sulfamethoxazole, and penicillins;

8. Known allergy to soy, milk- and/or egg;

9. Mental status that is incompatible with the proper conduct of the study;

10. Occupation involving handling of ETEC or Vibrio cholerae currently, or in the past 3 years;

11. Reported average stool frequency of <1 or >3 per day;

12. Symptoms consistent with Travelers' Diarrhea concurrent with travel to countries where ETEC infection is endemic (most of the developing world) within 3 years prior to dosing, OR planned travel to endemic countries during the length of the study;

13. Use of antibiotics, norit, laxatives (up till 6 months prior to inclusion), cholesterol lowering agents, antacids, proton pump inhibitors and immune suppressive agents (up till 3 months prior to inclusion);

14. Vaccination for or ingestion of ETEC, cholera, or E coli heat labile toxin within 3 years prior to inclusion;

15. Vegans.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

PanTheryx, Inc.

INDUSTRY

Sponsor Role: collaborator

NIZO Food Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Van Schaik

Role: STUDY_DIRECTOR

NIZO Food Research

Locations

NIZO

Ede, Gelderland, Netherlands

Countries

Netherlands

Other Identifiers

NL62453.028.17

Identifier Type: -

Identifier Source: org_study_id