Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03052439 |
| Other study ID # |
HUM00122970 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 5, 2017 |
| Est. completion date |
April 22, 2020 |
Study information
| Verified date |
November 2020 |
| Source |
University of Michigan |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Irritable bowel syndrome (IBS) is the most common gastrointestinal disease, affecting 12% of
the US population and up to 20% of the population worldwide. This is a condition that is
diagnosed based on specific symptoms of altered bowel habits and abdominal pain, as well as
the exclusion of select other GI diseases. IBS not only causes constipation, diarrhea,
abdominal cramping, and bloating, it also significantly affects quality of life, overall
functioning, and work productivity.
The cause of IBS is likely multifactorial, which makes it a difficult disease to treat.
However, patients often associate their IBS symptoms with eating a meal. Up to 90% of IBS
patients restrict their diet to prevent or improve their symptoms, and patients are
increasingly interested in more holistic approaches to disease management. At present, the
most persuasive evidence that dietary changes can treat IBS supports a diet low in
fermentable carbohydrates (the low FODMAP (fermentable oligo, di, and monosaccharides and
polyols) diet). This diet, which is low in certain carbohydrates, has been shown to improve
IBS symptoms (particularly abdominal pain and bloating), but can be difficult to follow and
quite restrictive. In addition, this diet is not meant to be used as a maintenance diet;
patients undergo an elimination phase followed by a reintroduction phase of specific
carbohydrate groups as they monitor their symptoms. From the results of our proposed study,
the study team hopes to arrive at a modified, less -restrictive version of the low FODMAP
diet that is equally effective, and also create a standard protocol that patients can use
during this reintroduction phase.
Patients with IBS will be recruited into a 13-week trial that would help determine the
optimal way in which high FODMAP foods should be introduced. After consent, patients would
start on a low FODMAP diet for 14 days, and if their symptoms improve, they would be invited
to continue in the study. For 7 days prior to the reintroduction of individual FODMAPs,
patients will ingest 1daily servings of a low FODMAP nutrition drink to validate the low
FODMAP content of this dietary supplement. If patients do not experience a flare of symptoms
with the supplement, they enter the reintroduction period. During this period, subjects would
introduce different groups of FODMAPs in a blinded fashion while remaining on an otherwise
low FODMAP diet while monitoring their IBS symptoms. At the end of the study period, subjects
would be informed of the FODMAPs to which they were sensitive and would meet with a
dietitian. At the completion of the study, the investigators would compile the data and
determine which FODMAPs were mostly likely to exacerbate IBS symptoms, thus providing the
construct for a modified low FODMAP diet, or "low FODMAP-Light." It is hoped that this
modified, less restrictive version of the low FODMAP diet would be equally effective for the
majority of IBS patients.
Description:
Research Plan Design: Blinded FODMAP reintroduction study Duration of study: 1 year
Patient population:
Eligible IBS patients
Visit 1 (-2 weeks): After providing written informed consent, baseline and descriptive data
will be obtained including age, sex, race, pertinent medical history, prior IBS treatments,
vital signs, weight, use of concurrent medications and supplements, duration of symptoms, and
baseline symptoms. The investigators will also collect blood, stool and urine for a series of
separately funded translational studies assessing immune activation, permeability, and
microbiome.
After this visit, patients will enter a two-week screening period during which severity of
symptoms will be assessed. Eligible patients will rate their average daily abdominal
pain/discomfort as a 4 or higher on an 11 point numerical rating scale (NRS) (0-no pain,
10-intolerable pain) and IBS subtype of constipation-predominant, diarrhea- predominant, or
mixed bowel habits (by Rome IV criteria19). Patients with an indeterminate subtype will be
excluded. Patients will record symptoms (Table 1) daily using a web-based survey instrument.
Experience from previous diet trials suggests that approximately 50% of participants will not
fulfill these inclusion criteria after the screening period, and will be termed screen
failures.
Visit 2 (weeks 0-2): IBS patients who fulfill the entry criteria will be invited to
participate in the remainder of the trial. Instruction from an experienced research dietitian
pertaining to the low FODMAP diet will be administered to all participants in an open-label
fashion for 2 weeks. Patients are to continue to record symptoms daily. Our previous work has
demonstrated that abdominal pain and bloating are the most responsive symptoms to the low
FODMAP diet. As such, the primary measure for this study will be improvement in abdominal
pain with improvement in bloating as a key secondary endpoint. If a subject experiences a
≥30% reduction in abdominal pain during the 2-week low FODMAP intervention compared to
baseline, they will be invited to participate in the blinded, FODMAP reintroduction phase
(below). If this ≥30% reduction is not obtained, this period of open-label low FODMAP diet
will be extended an additional 2 weeks to ascertain if their symptoms improve to qualify for
continuation.
Standard dietary compliance measures used in the counseling environment are to include
prospectively recorded 3-day food diaries before and after the open label period. Body weight
over the course of the study will also be followed. Food diaries will be analyzed for
compliance via the Nutrition Data System for Research (NDSR) computer program, measuring
fructose, lactose, sucrose, pectins, sorbitol, and added sugars. Blood, stool and urine
samples will be collected for translational studies (separately funded).
Week 2: If a ≥30% reduction in abdominal pain is obtained from the low FODMAP diet, subjects
will be eligible to continue in the study during which they will remain on a full FODMAP
elimination diet. For 7 days (week 2-3) prior to the reintroduction of individual FODMAPs,
subjects will ingest 1 daily servings of a low FODMAP nutrition drink (Pronourish, 170
calories each, Nestlé S.A., Vevey, Switzerland) to validate the low FODMAP content of this
dietary supplement. Daily symptoms will be measured as above. If a participant does not
experience a flare of symptoms with the supplement, they will continue onto the
reintroduction phase. If the participant does experience a flare in symptoms, they will
discontinue the product for 1 week before continuing in to the next phase (reintroduction
phase) of the study. The supplement will be supplied with an unbranded label. Adverse events
will be monitored during weeks 2-3 and significant adverse events (discontinuation of the
supplement, worsening of GI symptoms back to baseline) will be recorded.
Visit 3 (weeks 3-13): FODMAP reintroduction (lactose, fructose, fructans, polyols, galactans)
will be achieved by providing subjects with similar appearing and similar tasting snacks
which will contain specific types of supplemental FODMAPs prepared by research dieticians at
MCRU. The study team will ask the participants to continue on their low FODMAP diet during
this reintroduction phase, with the addition of 1-2 supplemental low FODMAP drinks per day
for convenience. The re-introduction of FODMAP containing foods will be conducted in a
double-blind fashion where both subjects and investigators will be unaware of the type of
FODMAP being reintroduced. The study dietitians will remain un-blinded to the subjects'
FODMAP treatment since they will be responsible for preparing and providing the FODMAP
containing supplement to the subjects. For the first 7 days of the re-introduction phase,
subjects will receive a FODMAP containing food item; this treatment will be followed by a
7-day wash out period during which subjects will receive a similar food or supplement that
does not contain the targeted FODMAP. The daily dose of fermentable carbohydrate contained in
the study food or supplement will be administered in 2 doses (moderate for the first 3 days
and higher amount for the later 4 days of the 7 day reintroduction period), with the content
similar to that found in the typical American diet (internal data from healthy study
subjects, published data18,20). To determine optimal dosing, the study team will conduct a
careful systematic review and interviews with experienced dieticians and GIs to determine the
optimal dose to each FODMAP with which to challenge. The order in which each specific FODMAP
is tested will be randomized to minimize the chances of an order effect. Throughout the study
period, symptom data will continue to be recorded on a daily basis (Table 1). If a subject is
unable to tolerate any portion of the reintroduction phase, they will discontinue
reintroduction of that specific FODMAP and revert again to a low FODMAP diet for washout.
Visit 4: Final study visit (13 weeks). Subjects will be unblinded as to which FODMAP
components exacerbated symptoms, if any. This information will be disseminated to study
participants by our dietitians immediately after their completion of the study period. The
primary investigators remain blinded to this information through analysis of data. A
three-day food diary will be obtained to ensure ongoing compliance with the low FODMAP diet.
Serum samples for immune activation, stool for microbiome analysis, urine for metabolome
analysis will be collected at Visit 2 and 3 and analyzed with funding from alternate sources.
Body weight will again be assessed.
