PTM202 and Modulation of Host Resistance to Diarrheagenic E. Coli (APA12/PANTER)

PTM202 and Modulation of Host Resistance to Diarrheagenic Escherichia Coli in a Randomized, Double-blind, Placebo Controlled Study in Healthy Human Subjects

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.

Study Overview

• Status: Completed
• Conditions: Traveler's Diarrhea
• Intervention / Treatment: Biological: E. coli strain E1392-75-2A; Device: PTM202

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).

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Ede, Gelderland, Netherlands, 6718ZB
      • NIZO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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).	Biological: 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).
Experimental: 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).	Biological: 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).; Device: PTM202; PTM202 is a dietary formula containing a proprietary mixture of dried bovine colostrum and dried whole egg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stool consistency	Change in stool consistency score (questionnaire) before and after E. coli challenge	Before challenge (Day 11-13), After challenge (Day 14-18)
Relative fecal wet weight	Change in relative fecal wet weight (freeze-drying) before and after E. coli challenge	Before challenge (Day 11-13), After challenge (Day 14-18)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stool frequency	Change in stool frequency (questionnaire) before and after E. coli challenge	Before challenge (Day 11-13), After challenge (Day 14-18)
Total fecal wet weight	Change in total fecal wet weight (wet weight measurement) before and after E. coli challenge	Before challenge (Day 11-13), After challenge (Day 14-18)
Gastro-intestinal symptoms	Change in gastro-intestinal symptoms (questionnaire) before and after E. coli challenge	Before challenge (Day 11-13), After challenge (Day 14-18)

Collaborators and Investigators

• Sponsor: NIZO Food Research
• Collaborators: PanTheryx, Inc.
• Investigators: Study Director: Van Schaik, NIZO food research

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2017
• Primary Completion (Actual): January 23, 2018
• Study Completion (Actual): March 16, 2018

Study Registration Dates

• First Submitted: September 15, 2017
• First Submitted That Met QC Criteria: September 28, 2017
• First Posted (Actual): October 4, 2017

Study Record Updates

• Last Update Posted (Actual): July 18, 2018
• Last Update Submitted That Met QC Criteria: July 17, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Nutrition; Gastroenteritis; E. coli; Traveler's diarrhea
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea
• Other Study ID Numbers: NL62453.028.17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes