APA12/PANTER* study: ""PTM202 and modulation of host resistance to diarrheagenic Escherichia coli in a randomized placebo-controlled trial in healthy human subjects"

Diarrhea is an important cause of morbidity and mortality in all regions of the
world and among all ages. The annual number of enterotoxigenic Escherichia coli
(ETEC) cases in the developing world was estimated at 840 million, with another
50 million asymptomatic carriers in children aged <5 years. Food-borne
infections are also frequently encountered by travelers to tropical countries,
with incidences up to 80%. Travelers* diarrhea is the most common health
impairment in persons visiting developing countries, affecting up to 50-90% of
travelers in high risk areas. Antibiotics can be a form of treatment, but the
growing resistances of pathogens against antibiotics is a drawback. Enhancement
of human resistance to food-borne infections by functional food ingredients is
therefore an attractive option.

To study whether PTM202, a dietary formula containing a proprietary mixture of
dried bovine colostrum and dried whole egg, improves the resistance of humans
to traveller*s diarrhea as caused by diarrheagenic E. coli. PTM202 contains
specific immunoglobulins that target rotavirus, enterotoxigenic E. coli,
shigatoxin-producing E. coli and Salmonella.

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). 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 a standardized evening meal and 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 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.

During the entire study, subjects will be instructed to maintain their habitual
diet, except for their dairy intake. Dairy has a high calcium content and
contributes significantly to total daily calcium intake. These dietary
guidelines will limit calcium intake on average to 500 mg/day. At study day 14,
after an overnight fast, all subjects will receive an inoculation of the
diarrheagenic E. coli (1E10 CFU (n=72) at study day 14). At study day 14, 15
and 16, subjects will receive either placebo or PTM202, a dietary formula
containing a proprietary mixture of dried bovine colostrum and dried whole egg.

Diarrheagenic E. coli strain E1392-75-2A
The strain used at NIZO food research, the diarrheagenic E. coli strain
E1392-75-2A, is a spontaneous mutant with deletion of the genes encoding the LT
and ST toxins, and can therefore not produce any toxins.
NIZO food research has previously performed 7 nutritional intervention studies
(n=305 subjects) in humans with E. coli strain E1392/75(2A). In the previous
studies, the diarrheagenic E. coli strain transiently induced symptoms of a
food borne infection increasing infectious diarrhea, fecal pathogen excretion,
stool frequency, Bristol Stool Score, and reported symptoms. All recorded
disease episodes were self-limiting and did not require early antibiotic
treatment. No treatment-related serious adverse events were reported during
these studies. The diarrheagenic E. coli strain E1392-75-2A strain is sensitive
to Ciprofloxacin which is a commonly used antibiotic in case of treatment of
this kind of E. coli infections.

PTM202
Both dairy and egg ingredients of PTM202 & soy protein based isonitrogenous
placebo have the potential to cause allergic responses in sensitive
individuals, including severe and anaphylactic reactions. Individuals with
known sensitization to either milk, egg or soy protein will be excluded, and we
anticipate that the majority of subjects will have had prior exposure to both
as part of normal diet. PTM202 should be avoided by those with intolerance to
lactose. Most clinical studies report no adverse effects from bovine colostrum
although minor side effects including nausea and flatulence have been rarely
reported. Soy protein may have allergic symptoms like skin redness (rash),
hives, itching, abdominal pain, diarrhea, nausea or vomiting, wheezing, runny
nose etc. For most people, soy allergy is uncomfortable but not serious.
Rarely, an allergic reaction to soy can be life-threatening.