Clearance of the probiotic strain Escherichia coli Nissle 1917 in the gastrointestinal tract of healthy volunteers
- Conditions
- Healthy volunteers trial, intended indication: Colitis ulcerosa in phase of remission, Chronic constipationTherapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2016-001240-19-BG
- Lead Sponsor
- Synlogic
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
1.No pre-existing medical conditions based on medical history and physical examination
2.Non-smoking
3.Male and female volunteers, aged 18-55 years
4.Normal weight according to the BMI (accepted range 18.5 to 30.0 kg/m2)
5.Regular bowel habits including consistency, frequency (4-14 stools per week)
6.Willingness to commit to no major dietary changes to daily carbohydrate and protein intake during the trial and until 2 weeks after last administration
7.Negative pregnancy test for all females of childbearing potential at entry visit
8.Signed written informed consent by subject
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 58
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1.Use of Mutaflor (or any other probiotic product) within 12 months prior to study initiation
2.Use of any investigational drug or antibiotics within 60 days prior to study initiation
3.Baseline EcN positivity by PCR assay of stool sample
4.Active infection (viral or bacterial)
5.Active GI disease (current or within past 6 months) including nausea, vomiting, diarrhea, constipation, abdominal pain, malabsorption, GI bleeding, inflammatory bowel disease, or any other condition that could affect Mutaflor passage or activity in the GI tract or cause fluctuations in GI signs/symptoms
6.Any previously diagnosed inflammatory bowel disease or irritable bowel syndrome
7.Major surgery of the gastrointestinal tract except for appendectomy
8.History of immune-compromised condition (e.g., AIDS, lymphoma, subjects undergoing corticosteroid treatment)
9.Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies
10.Hypersensitivity to the active substance in Mutaflor or to any of the excipients
11.Allergic diathesis or any clinically significant allergic disease (i.e. asthma or bronchial hyperreactivity)
12.Laboratory values outside the normal range that are determined to be clinically significant by the investigator
13.Other severe chronic medical conditions or other active diseases that should be excluded, based on clinical assessment of the investigator
14.Systolic blood pressure outside the range of 100 to 140 mmHg and/or diastolic blood pressure outside the range of 60 to 90 mmHg at entry visit
15.Heart rate outside the range of 50 to 90 beats/min at entry visit
16.Body temperature (axillary) outside the interval of 35.5 to 37.1°C at entry visit
17.Any clinically significant abnormality of the resting ECG (12-lead) (i.e. AV block, 2° to 3°, sinus bradycardia, sick sinus syndrome, SA block)
18.Special diet due to any reason, e.g. vegetarians
19.Subjects expected not to be able to fulfil study specific restrictions given in chapter 9.4 Restrictions of the study protocol
20.Pregnant and/or nursing women. Positive pregnancy test on day 0
21.Fertile women without reliable contraception method.
List of medically accepted contraceptive methods (used at least 4 weeks prior entry visit and not to be changed for the duration of the study):
a.combination of 2 barrier methods: female/male condoms, diaphragms, spermicides
b.hormonal methods: combined estrogen/progestin injectable and oral contraceptives, progestin injectable and oral contraceptives, Norplant implants, skin patches, NuvaRing®
c.intrauterine devices (IUD): inert or copper-releasing or progestin-releasing IUD
d.voluntary sterilization (female tubal occlusion)
22.History of drug abuse or use of illegal drugs: use of soft drugs, e.g. marihuana within 6 months of screening or hard drugs, e.g. cocaine, amphetamines, phencyclidine within 1 year of screening
23.Alcohol abuse, i.e. regular use of more than 2 units of alcohol per day or 10 units per week or a history of alcoholism (one unit of alcohol equals 250 ml beer, 125 ml wine or 25 ml spirits) or recovered alcoholics
24.Positive drug screening and/or positive alcohol test at entry screening or on day 0
25.Subjects who are known or suspected:
a.not to comply with the study directives
b.not to be capable of understanding and evaluating the information given to them as part of the formal information policy (informed con
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the clearance of Escherichia coli strain Nissle 1917 in the gastrointestinal tract after administration of an oral test preparation containing 2.5-25 x 10^9 CFU (Test IMP: Mutaflor® capsules) after single or multiple dose administrations of one capsule three times daily for 28 days (48 volunteers) or for 1 day (10 volunteers) taken together with meals;Secondary Objective: Not applicable;Primary end point(s): 1.Percentage of volunteers with a stool sample positive for Escherichia coli strain Nissle 1917, 24 weeks after the start of treatment;<br>2.Time to no detection of EcN in the stool<br>;Timepoint(s) of evaluation of this end point: After completion of the clinical part of the trial and database lock
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: Not applicable