Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02793193 |
| Other study ID # |
PITN-GA-2013-607652 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2/Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
July 2016 |
| Est. completion date |
January 2018 |
Study information
| Verified date |
May 2016 |
| Source |
University Hospital Tuebingen |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The gut-brain axis is described as being important in both, gut functions and central nervous
system (CNS) functions. The microbiota in the gut plays an important role in this axis
through neural, immune and endocrine systems. Previous studies have found altered gut
microbiota (GM) composition could change the CNS functions in animals and humans. Probiotics
were shown having positive effect on improving stress response in animals and stress related
psychiatry in humans. The current study will investigate if probiotics can improve response
to social stress in healthy participants and patients with irritable bowel syndrome (IBS),
which is a stress-related disease, and whether this probiotic action can be counteracted by
the locally acting antibiotic, Rifaximin. The investigators will use the Cyberball paradigram
to induce social stress and magnetoencephalography (MEG) to record neural responses related
to the social stress. The administration of the probiotics will be a new strategy for both
the mental health management and treatment of gastrointestinal (GI) disorders in the future.
Description:
Understanding the neural mechanisms underlying the experience of social stress may help to
prevent the development of IBS and to help people to maintain their mental health. Social
distress has been examined with the Cyberball paradigm in developing peers and children with
autism spectrum disorders, people with social anxiety disorder and with borderline
personality disorder. These studies provided researchers the clinical evidence and validity
of the paradigm in patients . Here the investigators will examine the neural response of
healthy volunteers to acute stress induced by the Cyberball game and if acute intervention
with probiotics for 4 weeks can alleviate the stress response. The study will be firstly
conducted on healthy volunteers whose GM will be disturbed by an antibiotic Rifaximin as to
simulate IBS patients, to see their neural response to the social exclusion (Study 1). The
second study will be conducted as a clinical trial in healthy volunteers to investigate the
effect of the probiotic Bifidobacterium longum 1714 (Study 2).
Study 1 & 2 will be a randomized, double blind, double dummy design, during which the
participants will visit the laboratory for 2 times (M1, M2,): measurement at baseline and
after intervention. Intervention period lasts for 1 week in study 1 and 4 weeks in study 2.
In study 1, Group 1 will take Rifaximin for 1 week Group 2 will take Placebo for 1 week
In study 2, Group 1 will take B.longum 1714 for 4 weeks Group 2 will take Placebo for for 4
weeks
Participants will be not allowed to eat certain kinds of food. As mentioned in the exclusion
criteria, participants will not eat probiotic/prebiotic containing food supplements, or
potentially immune-enhancing dietary supplements either. The food to be avoided will be
summarized on a list of probiotic/prebiotic containing food. Also, participants will be asked
to record the food they take on each day during the intervention, by taking photos.
Nutritional information about the food taken by the participants will be analyzed by using an
online tool http://nutritiondata.self.com/.
Before the intervention period, each participant will need to complete questionnaires
including a demographic questionnaire, the Patient Health Questionnaire (PHQ) and the
Hospital Anxiety and Depression Scale (HADS). The PHQ is for excluding those healthy
participants who suffer from psychiatry disorder(s) and for further analysis. The HADS, which
will also be completed after each intervention period, aims to study the effect of the
probiotic on anxiety and depression level in healthy participants and especially in IBS
patients. Also, participants will receive a daily online questionnaire via email, including
the Positive Affect and Negative Affect Scales, and questions about their level of stress,
consumption of the study capsules, hours of sleep, IBS symptom and quality of life (QoL) (the
last two are only for patients), etc. Through questionnaires, the investigators will record
menstruation information of female participants for controlling confounders. Also, gender and
age between healthy and patient groups will be matched as much as possible, since these
factors could have an effect on the GM composition and the CNS functions.
Stool samples will be collected on the day participants come to a lab visit for measurements.
The stool sample should be as fresh as possible, ideally collected in the morning of the
visiting day. Fresh samples will be stored in RNA synthesis stabilization buffer at the time
of collection. A centrifuged fecal pellet will be stored at -80°.
During the Magnetoencephalography measuring, before the Cyberball game, there will be a
resting state session for 5 minutes. In this session participants will be studied in supine
position. Participants will be instructed to move as little as possible and remain awake,
while keeping their eyes closed. After the resting state recording the Cyberball game will
start. The task of the game will be projected on a screen and participants will be asked to
fixate the screen and hold a response box to get ready for the task. Magnetic fields will be
measured with a 275-channel whole head magnetometer at a sampling rate of 1200 Hz. In order
to overlay the brain activity derived from MEG on anatomical scans, a high-resolution (1 mm,
isotropic) T1-weighted structural MR image will be acquired with an MPRAGE sequence with a
3-T MR scanner (University Hospital Tübingen, Tübingen, Germany).
7 participants will be needed in each experimental group in study 1, resulting in at least 14
in study 1. 20 participants will be needed in each experimental group in study 2, resulting
in at least 40 in study 2. The recruitment of participants will be organized by the MEG
center under the responsibility of Prof. Dr. Christoph Braun. The study will be announced on
black boards in the Tübingen University Clinic and the campus of the University. Further
announcements will be done via the University mailing list and the local newspaper. Each
participant will be provided with detailed information about the aims of the investigation,
the tasks and measurements. Participants will be informed about the possibility to cancel the
examination at any time without cause or prejudice for her person. Investigation will be
carried out only when written consent from the participants is obtained.
