Crohn's Disease, Inflammatory Bowel Disease
Conditions
Keywords
Crohn's disease, Fructooligosaccharide, Inulin, Diet, Treatment, Bacterial flora, Oxidative stress
Brief summary
Our objective is to determine whether a specific dietary intervention or a fructooligosaccharide (FOS) supplement has anti-oxidant or prebiotic effects and whether it is beneficial in the treatment of Crohn's Disease (CD.
Detailed description
Several epidemiological studies and therapeutic observations in the complementary and alternative medicine (CAM) literature suggest that diet is key to development of CD and its treatment. The investigators took advantage of these CAM recommendations and designed dietary interventions. Our preliminary open label studies in IBD patients showed that our interventions are acceptable and well-tolerated and result in improvement, reducing symptoms and/or the degree of inflammation. The investigators are now seeking to validate this finding and determine the mechanisms underlying the effects of dietary manipulation-such as potential effects on colonic bacterial microflora. In another pilot study using 16s rDNA bacterial fingerprinting, the investigators demonstrated that the intestinal microflora of patients with CD differ significantly from healthy individuals. Whether the investigators can normalize/change the microflora of CD patients with dietary therapies, however, remains to be determined. Accordingly, the investigators designed a double blind placebo controlled study to test the hypotheses that: (1) dietary manipulation with either diet or a FOS supplement is an effective CAM therapy that prevents CD relapse (leads to maintenance of remission) and (2) such dietary manipulation can normalize the microflora of CD patients and decrease mucosal oxidative damage. 90 participants are expected to undergo the trial and have a 2:1 chance of receiving active therapy. The trial is seeking to enroll participants with inactive CD who have been medically induced into remission within 9 months of enrollment. Participants must be on their Crohn's medications at a stable dose for 3 months, which does not include steroids (e.g. Prednisone, Entocort) or antibiotics at the time of enrollment. Participants will be followed till relapse occurs or up to 52 weeks. Participants are asked to fill out a variety of questionnaires, keep a food and adverse event diary, and have a research, limited, unprepped flexible sigmoidoscopy for colonic tissue collection at the beginning and end of the study period. Significance. This study could provide information to suggest diet or dietary supplement as a safe therapy for IBD and lay the groundwork for more definitive, randomized, controlled trials.
Interventions
DRUGActive fructo-oligosaccharide
2 teaspoons of active fructo-oligosaccharides daily and Time and attention administering usual dietary recommendations for a healthy diet based on 2005 Dietary Guidelines for Americans
DRUGPlacebo fructo-oligosaccharide
2 teaspoons of placebo fructose powder ( to serve as the placebo equivalent of active treatment with fructo-oligosaccharides daily) and Time and attention administering usual dietary recommendations for a healthy diet based on 2005 Dietary Guidelines for Americans
DIETARY_SUPPLEMENTDiet
A restrictive anti-inflammatory diet developed by the research team and 2 teaspoons of placebo fructose powder ( to serve as the placebo equivalent of active treatment with fructo-oligosaccharides daily)
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
Rush University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Documented ileocolonic or colonic CD based on classical history and classical endoscopic or surgical findings and histology compatible with CD; 2. Induction of remission with medical therapy within 9 months of the study; 3. Inactive CD for at least 2 weeks with CDAI score less than 150; 4. No change in IBD medication doses for 3 months; 5. No change in smoking habits a month prior to enrollment (because smoking may exacerbate CD) and acceptance of not-changing smoking habits during the term of the study).
Exclusion criteria
1. Patients with history of bowel obstruction and/or known strictures (as the high fiber content may precipitate obstruction); 2. Patients with extensive colonic or ileocolonic resection; 3. Patients with ileostomies or colostomies with diverted fecal stream; 4. Patients with isolated perianal/anorectal disease; 5. Patients with surgically induced remission; 6. Concomitant infection (e.g., C. difficile colitis); 7. Use of antibiotics within 4 weeks, or steroids, herbal remedies or diet therapies within 2 weeks of the onset of the trial or during the study; 8. Use of potential IBD exacerbators such as NSAIDs within 1 wk of the study; 9. Acute illness requiring immediate hospitalization for CD or other reasons; 10. Presence of symptomatic organic GI disease other than CD, hemorrhoids, hiatal hernia; GERD; 11. Pre-existent organ failure or severe comorbidities as these may change Gl flora: * Liver disease (cirrhosis or persistently abnormal AST or ALT that are 2X\> normal); * Kidney disease (creatinine\>2.0 mg/dL); * Uncontrolled psychiatric illness; * Clinically important lung disease or heart failure; * HIV disease; * Alcoholism; * Transplant recipients; * Patients receiving other immunosuppressant medications for comorbidities (e.g. Enbrel for rheumatoid arthritis); 12. Presence of short bowel syndrome or severe malnutrition with ideal body weight less than or equal to 90% or predicted; 13. Estimated survival \<1 year and Karnofsky performance status \<50%; 14. Desire to become pregnant during study or current pregnancy or nursing; 15. Desire to change smoking-status during the study; 16. Daily use of anticoagulation and antiplatelet medications; 17. Complicated IBD with anticipation of imminent surgical intervention during the term of the study; 18. Inability to have a regular follow-up and comply with study requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Flare Up of Crohn's Disease Through Month 12 | Up to 12 months | The efficacy of the dietary treatment was assessed by looking at the number of participants who flared. |
| Quality of Life in Patients Taking Dietary Treatments | At exit visit of study | Inflammatory Bowel Disease Questionnaire (IBDQ) overall scores at the exit visit of the study.It consists of 32 questons divided into four dimensions: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items) and social function (5 items). Every question has graded responses from 1 (worst situation) to 7 (best situation), and thus the total score is ranging from 32 to 224 with higher scores representing better quality of life. |
| Safety of Dietary Treatments | 90 days | Data not collected |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Ileocolonic Flora | 90 days | Data not collected |
Countries
United States
Participant flow
Recruitment details
54 subjects were randomized into a 12 month randomized, double blind, placebo controlled trial to test the efficacy of a specialized restrictive diet and a Fructo-oligosaccharide (FOS) supplement in maintenance of remission in patients with Crohn's disease (CD). Participants were recruited at Rush University, Chicago between Sept 2005-2012.
Participants by arm
| Arm | Count |
|---|---|
| Time and Attention + Active Fructooligosaccharide Supplement. Time and attention + active fructooligosaccharide supplement.
Time and attention + active fructooligosaccharide supplementation: 2 teaspoons of fructooligosaccharides daily | 19 |
| Time and Attention + Fructooligosaccharide Placebo Time and attention + fructooligosaccharide placebo
Time and attention + fructo-oligosaccharide placebo: 2 teaspoons of placebo powder daily | 19 |
| Dietary Therapy + Fructooligosaccharide Placebo Dietary therapy + fructooligosaccharide placebo
dietary therapy + fructo-oligosaccharide placebo: Medical nutrition therapy and 2 teaspoons of placebo powder | 16 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Flare up | 6 | 4 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Pregnancy | 1 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 3 | 4 |
Baseline characteristics
| Characteristic | Dietary Therapy + Fructooligosaccharide Placebo | Time and Attention + Active Fructooligosaccharide Supplement. | Time and Attention + Fructooligosaccharide Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 3 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 17 Participants | 16 Participants | 47 Participants |
| Age, Continuous | 45.13 years STANDARD_DEVIATION 14.17 | 43.21 years STANDARD_DEVIATION 12.43 | 48 years STANDARD_DEVIATION 16.89 | 45.46 years STANDARD_DEVIATION 14.51 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 19 Participants | 14 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 2 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 15 Participants | 16 Participants | 43 Participants |
| Region of Enrollment United States | 16 participants | 19 participants | 19 participants | 54 participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 13 Participants | 33 Participants |
| Sex: Female, Male Male | 6 Participants | 9 Participants | 6 Participants | 21 Participants |
| Smoking Non-smokers | 16 participants | 16 participants | 18 participants | 50 participants |
| Smoking Smokers | 0 participants | 3 participants | 1 participants | 4 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 19 / 19 | 19 / 19 | 16 / 16 |
| serious Total, serious adverse events | 2 / 19 | 1 / 19 | 0 / 16 |
Outcome results
Primary
Number of Participants With Flare Up of Crohn's Disease Through Month 12
The efficacy of the dietary treatment was assessed by looking at the number of participants who flared.
Time frame: Up to 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Time and Attention + Active Fructooligosaccharide Supplement | Number of Participants With Flare Up of Crohn's Disease Through Month 12 | 6 participants |
| Time and Attention + Fructooligosaccharide Placebo | Number of Participants With Flare Up of Crohn's Disease Through Month 12 | 4 participants |
| Dietary Therapy + Fructooligosaccharide Placebo | Number of Participants With Flare Up of Crohn's Disease Through Month 12 | 0 participants |
Primary
Quality of Life in Patients Taking Dietary Treatments
Inflammatory Bowel Disease Questionnaire (IBDQ) overall scores at the exit visit of the study.It consists of 32 questons divided into four dimensions: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items) and social function (5 items). Every question has graded responses from 1 (worst situation) to 7 (best situation), and thus the total score is ranging from 32 to 224 with higher scores representing better quality of life.
Time frame: At exit visit of study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Time and Attention + Active Fructooligosaccharide Supplement | Quality of Life in Patients Taking Dietary Treatments | 180.17 units on a scale | Standard Deviation 24.78 |
| Time and Attention + Fructooligosaccharide Placebo | Quality of Life in Patients Taking Dietary Treatments | 197.42 units on a scale | Standard Deviation 22.55 |
| Dietary Therapy + Fructooligosaccharide Placebo | Quality of Life in Patients Taking Dietary Treatments | 196 units on a scale | Standard Deviation 18.52 |
Primary
Safety of Dietary Treatments
Data not collected
Time frame: 90 days
Population: Data not Collected
Secondary
Changes in Ileocolonic Flora
Data not collected
Time frame: 90 days
Population: Data not collected