Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01252550 |
| Other study ID # |
NU341 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
December 2, 2010 |
| Last updated |
November 17, 2014 |
| Start date |
May 2010 |
| Est. completion date |
August 2014 |
Study information
| Verified date |
November 2014 |
| Source |
Sahlgrenska University Hospital, Sweden |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Sweden: Regional Ethical Review Board |
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of this study is to investigate the association between gut microbiota,
immunology and typical pathophysiological factors in patients with IBS (all subtypes) AND to
assess the effect of Activia consumption on GI symptoms provoked by a lactulose challenge
test in IBS patients.
Description:
BACKGROUND
There is a wide variety of symptoms in IBS, irritable bowel syndrome, both among individuals
and in the symptoms of a specific individual. Pathophysiological factors that are of
importance have been identified in IBS, but all of the factors do not occur in the
symptomatology of all patients. Visceral hypersensitivity, deviant motor and secretion
function in the gastrointestinal tract as well as psychological factors are believed to be
of importance. However the relative importance of specific factors in the symptomatology is
not elucidated.
Deviations in the autonomic and central nerve function have also been demonstrated in IBS,
along with low grad inflammation, immunological anomalies, and changes in the
microbiological gut flora. The importance of these factors in developing the more
established pathophysiological factors, visceral hypersensitivity, and deviated
gastrointestinal motor and secretion functions have not yet been studied. Neither have the
interactions between the autonomic and central nerve functions or the significance of these
functions in IBS.
In response to the recent findings, regarding deviant microbiological gut flora in IBS, the
use of probiotics as treatment has been tested, with altering outcome. The effects of some
products are positive, but far from all the patients with IBS get sufficient relief. The
response of treatment with probiotics cannot be predicted with the methods available today;
in example it is not possible to predict which patient will respond to the treatment and
what the mechanisms behind the symptom relief are.
Questions
- What affects the symptomatology in IBS?
- Visceral hypersensitivity
- Deviant colonic motor function
- Autonomic nerve dysfunction
- Central nerve dysfunction (especially in the level of the brain stem)
- Psychological factors
- Coping
- Demography (sex, age)
- Immunological deviations in peripheral blood/intestine
- Deviations in the composition of the microbiological gut flora
- Sexual/physical abuse
- What are the interactions between pathophysiological deviations in IBS?
- Can the treatment response of probiotics be predicted?
- Why do probiotics give relief to some of the patients with IBS?
INVESTIGATION
1. A structured investigational model, covering the most important pathophysiological
factors in IBS and clarifying the symptomatology of the patients in detail.
2. A randomized, double blinded placebo controlled study, evaluating the effects of
probiotics (Bifidobacterium lactis) on the symptomatology in IBS as well as measuring
the effect probiotics have on the fermentation in the intestines, immunological
variables and the composition of the microbiological gut flora.
VISIT 1
- The patients are thoroughly informed regarding the context of the study and a written
consent is signed.
- Blood samples are taken to rule out any organic disease (Hb, LPK, TPK, Na, K, Crea,
Liver status, CRP, Transglutaminase antibodies).
- Validated questionnaires are completed
- IBS Symptom Severity Scale (IBS-SSS) - gastrointestinal and extra intestinal
symptoms
- Gastrointestinal Symptom Rating Scale - IBS (GSRS-IBS) - IBS specific GI-symptoms
- Hospital Anxiety and Depression Scale (HAD) - general anxiety and depression
- Visceral Sensitivity Index (VSI) - GI-specific anxiety
- Patient Health Questionnaire-15 (PHQ-15) - severity of somatisation, depression,
anxiety (panic anxiety, eating disorders and alcohol problems)
- IBS Quality of Life Questionnaire (IBSQOL) - disease specific health related
quality of life
- Fatigue Impact Scale (FIS) - impact of fatigue on quality of life
- Abuse Questionnaire - physical and sexual abuse
- Sense of Coherence Index - sense of coherence, coping
- ABR (Auditory Brain stem Response audiometry) - brain stem audiometry measuring the
electric activity in level of the brain stem while listening to different audio stimuli
(listening to sounds of clicks through headphones). Through this test the function of
the brain stem can be measured, its ability to mask the effect of disturbing noises
etc.
- Holter-ECG (24 h) - spectrum analysis to evaluate the autonomic nerve function; the
balance between parasympathetic and sympathetic nerve function.
- Permeability test of the intestine - the patient drinks a liquid solution of water and
sugars (50.0 g sucrose, 5.0 g mannitol, 10.0 g lactulose and 1.0 g sucralose in 200 ml
tap water), thereafter urine is collected during the following 9 h. The amount of
sugars found in the urine is a measurement of the permeability in the intestines. The
urine will be collected in separate containers depending on what time of the day it is,
and depending on the time the permeability in the small intestine respectively in the
large intestine can be measured separately.
- Registration of stool consistency and frequency over the following 2-3 weeks, until
visit 3, using the "Bristol Stool Form Scale" (BSF)
- Food journal are handed out - food intake over three consecutive days will be
registered by the patient.
VISIT 2
- Handing in urine - the last of the urine collected on visit 1 is being handed in by the
patient.
- Returning EKG-material - the Holter, recording EKG, is returned by the patient.
VISIT 3
- Salivary sample - test to measure the levels of cortisol, an important stress marker.
- Oro-anal transit time - 60 markers that can be seen through x-ray examination are being
swallowed prior to the visit (10 markers/day during 6 days) and in the examination it
is possible to see how many of the markers remain in the GI-tract and where in the
tract they are positioned. This is a way to measure the oro-anal transit time, which
mainly is determined by the colonic transit time. Thereby this is an indirect
measurement of the motor function in colon. Regional transit in different colonic parts
can be assessed by evaluating where in the colon the markers are.
- Rectal sensitivity testing - a balloon is placed in the rectum and is through a tube
attached to a so called barostat. By using the barostat it is possible to inflate and
deflate the balloon in a controlled matter and also to measure compression and volume
in the balloon. The compression and volume is being increased in a predetermined way
and the patient is asked to state how it feels by using VAS-scales; symptoms noted and
the intensity of these symptoms. The sensitivity in the rectum (large intestine) can be
described by valuing the levels of compression and volume that give rise to the
symptoms.
VISIT 4
- Sigmoidoscopy with biopsies. Macroscopic evaluation of the mucosa of the large
intestine, to rule out inflammatory bowel disease as a cause of the patients symptoms.
Biopsies from the rectum and sigmoid are collected to be analyzed in regards of
inflammatory cell populations and interleukins in the colonic mucosa, as well as amount
of bacteria in the mucosa. Molecular techniques will be used, such as 16sRNA.
- Stool sample - analysis of immunological and inflammatory markers in the faeces and of
the composition of the microbiological bacterial flora, this reflects the luminal
bacterial flora (16sRNA technique will be used).
- Blood samples - various immunological analysis, for example different pro- and
anti-inflammatory interleukins and different food related antibodies (IgE, IgG), are
done to evaluate toe immunological activity and propensity to react in an unfavorable
way when for instance consuming certain food items.
- Symptom protocol (IBS-SSS) and journal of stool consistency and frequency (Bristol
Stool Form Scale (BSF)) are handed out. Symptoms and stools will be registered during
1-3 weeks and will be used as basal values prior to the treatment period.
VISIT 5
- Lactulose challenge test - evaluation of symptoms and excretion of hydrogen and methane
gas in the exhaled air after intake of a liquid meal (400ml Nutridrink®, 1.5 kcal/ml)
containing 25 mg lactulose. Hydrogen and methane gas in the exhaled air is a
measurement of the degree of fermentation in the intestines, and indirectly can a
bacterial overgrowth in the small intestine be detected. This "challenge" test is more
of a physiological test to study the sensitivity of the GI-tract. The symptoms and
excretion of gas will be registered during 4 h.
- Stool sample - analysis of immunological and inflammatory markers in the faeces and of
the composition of the microbiological bacterial flora, this reflects the luminal
bacterial flora (16sRNA technique will be used).
- Salivary sample - test to measure the levels of cortisol, an important stress marker.
- Randomization of the patients as they are included in the treatment part of the study.
The patients will during 14 days have a daily intake of a yoghurt containing probiotics
(Bifidobacterium lactis, Activia®) or a yoghurt without probiotics (placebo), 125 g 2
times a day (morning and evening). During the treatment part the patients register
symptoms (Symptom protocol (IBS-SSS)) and stool consistency and frequency (Bristol
Stool Form Scale (BSF)).
VISIT 6
- Visit takes place on the last day of the treatment period.
- Lactulose challenge test is being repeated to evaluate potential differences in
symptoms and excretion of hydrogen and methane gas in the exhaled air after intake of a
liquid meal (400ml Nutridrink®, 1.5 kcal/ml) containing 25 mg lactulose.
- Stool sample - analysis of immunological and inflammatory markers in the faeces and of
the composition of the microbiological bacterial flora, this reflects the luminal
bacterial flora (16sRNA technique will be used).
- Blood samples - various immunological analysis, for example different pro- and
anti-inflammatory interleukins and different food related antibodies (IgE, IgG), are
done to evaluate toe immunological activity and propensity to react in an unfavorable
way when for instance consuming certain food items. Will be compared with previous
blood samples.
VISIT 7
• Summarizing visit - visit at a doctor specialized in functional GI-disorders. The results
from the tests and analysis of the previous visits are being evaluated and any potential
treatment is based on these results. The patients are offered a telephone based follow-up if
they want to, otherwise they are recommitted to the primary health care.
