Crohn Disease, Inflammatory Bowel Diseases, Ulcerative Colitis
Conditions
Brief summary
There is limited data to guide the use of dietary change in the management of IBD, and it can prove challenging to implement in the setting of altered anatomy, comorbid conditions, and patient compliance. Therefore there is an important need to study diet as a therapy for IBD. Here, the investigators propose a novel study to evaluate the feasibility and efficacy of the autoimmune protocol (AIP) diet in patients with active Crohn's disease (CD) and ulcerative colitis (UC).
Detailed description
The investigators propose a novel study to evaluate the feasibility and efficacy of the autoimmune paleo (AIP) diet in patients with Crohn's disease (CD) and ulcerative colitis (UC). Specific aims: 1. To evaluate the effect of the AIP diet on clinical and endoscopic disease activity for CD and UC, 2. To examine changes in inflammatory biomarkers during AIP diet 3. To characterize changes in RNA expression from intestinal mucosal biopsy specimens from prior to diet initiation to end of the study. 4. To characterize changes in fecal microbiome during diet intervention
Interventions
OTHERAutoimmune protocol (AIP) diet
Autoimmune protocol diet, designed as a 6 week step wise elimination phase followed by 5 week maintenance phase.
Sponsors
Scripps Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. At least 18 years of age 2. Able to provide written informed consent prior to screening and to comply with the requirements of the study protocol. 3. Established diagnosis of small bowel CD or colonic CD or ulcerative colitis 4. Confirmation of active CD or UC with recent (within 6 months of consent or prior to study start) objective evidence of endoscopically active disease on colonoscopy or computed tomography/magnetic resonance enterography or video capsule endoscopy 5. Any medications being currently used for IBD must remain stable during the study period with the exception of tapering of corticosteroids. 6. Current disease activity defined as a Harvey Bradshaw index ≥ 5 at baseline for CD or Partial Mayo Score ≥ 3 for UC 7. Established Facebook account 8. Comfortable with internet-based surveys and email
Exclusion criteria
1. If female, is pregnant or is breast feeding 2. Known celiac disease or subjects with a positive screen for celiac disease (elevated tissue transglutaminase antibodies) 3. Inability to provide informed consent or unwilling to participate 4. Evidence of untreated infection (e.g. Clostridium difficile) 5. Presence of stoma or J pouch 6. Bowel surgery within 12 weeks prior to enrollment and/or has surgery planned or deemed likely for inflammatory bowel disease during the study period 7. Use of tube or enteral feeding, elemental diet, or parenteral alimentation within 4 weeks prior to study initiation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Remission for Crohn's Disease | 11 weeks | Clinical disease activity scores will be measured by Harvey Bradshaw Index for patients with Crohn's Disease (CD). The Harvey Bradshaw Index measures general well being, abdominal pain severity, number of stools daily, presence of abdominal mass, and complications. The Harvey Bradshaw Index ranges from 0-16, with lower values representing better outcome and higher values representing more disease activity. Clinical remission is defined as Harvey Bradshaw Index \<5 for CD. |
| Number of Participants With Clinical Remission for Ulcerative Colitis | 11 weeks | Clinical disease activity scores will be measured by Mayo score for patients with ulcerative colitis (UC). The Mayo score includes measures of stool frequency, rectal bleeding, physician global assessment, and endoscopic assessment. The Mayo score ranges from 0-12, with lower values representing better outcome and higher values representing more disease activity. Clinical remission is defined as Mayo score 2 or less for UC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Inflammatory Biomarkers, Including Fecal Calprotectin (FC), During Dietary Intervention | 11 weeks | Number of Participants with a change in fecal calprotectin levels (inflammatory biomarker) from baseline to 11 weeks. |
| Number of Participants With Mucosal Healing for Crohn's Disease or Ulcerative Colitis | 11 weeks | Number of participants with Crohn's disease or ulcerative colitis who have absence of erosions or ulcers on endoscopy or imaging |
| Changes in Fecal Microbiome Composition During Dietary Intervention | 11 weeks | Changes in fecal microbiome composition at baseline and at weeks 2, 4, 6, and 11 using 16S ribosomal RNA sequencing |
| Major Biological Processes Gene Ontology Terms Enriched in Downregulated and Upregulated Genes | 11 weeks | Description of changes in RNA expression from colonic biopsies from patients with ulcerative colitis from baseline to end of study (11 weeks). Specifically, examined top 10 major Biological Processes Gene Ontology Terms Enriched in Downregulated and Upregulated Genes |
| Changes in Inflammatory Biomarkers, Including C-reactive Protein (CRP), During Dietary Intervention | 11 weeks | Number of Participants with a change in C-reactive Protein Levels (inflammatory biomarker) from baseline to 11 weeks. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Autoimmune Protocol (AIP) Diet Adult patients with active Crohn's disease or ulcerative colitis, undergoing 11 week autoimmune protocol diet, to examine therapeutic efficacy
Autoimmune protocol (AIP) diet: Autoimmune protocol diet, designed as a 6 week step wise elimination phase followed by 5 week maintenance phase. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Autoimmune Protocol (AIP) Diet |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 44 years STANDARD_DEVIATION 19 |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 1 / 15 |
| serious Total, serious adverse events | 1 / 15 |
Outcome results
Primary
Number of Participants With Clinical Remission for Crohn's Disease
Clinical disease activity scores will be measured by Harvey Bradshaw Index for patients with Crohn's Disease (CD). The Harvey Bradshaw Index measures general well being, abdominal pain severity, number of stools daily, presence of abdominal mass, and complications. The Harvey Bradshaw Index ranges from 0-16, with lower values representing better outcome and higher values representing more disease activity. Clinical remission is defined as Harvey Bradshaw Index \<5 for CD.
Time frame: 11 weeks
Population: In this study, 9 out of the 15 participants had Crohn's disease. The other 6 participants had ulcerative colitis, so were not included in this subgroup analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With Crohn's Disease | Number of Participants With Clinical Remission for Crohn's Disease | 6 Participants |
Primary
Number of Participants With Clinical Remission for Ulcerative Colitis
Clinical disease activity scores will be measured by Mayo score for patients with ulcerative colitis (UC). The Mayo score includes measures of stool frequency, rectal bleeding, physician global assessment, and endoscopic assessment. The Mayo score ranges from 0-12, with lower values representing better outcome and higher values representing more disease activity. Clinical remission is defined as Mayo score 2 or less for UC.
Time frame: 11 weeks
Population: In this study, 6 out of the 15 participants had ulcerative colitis. The other 9 participants had Crohn's disease, so were not included in this subgroup analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With Crohn's Disease | Number of Participants With Clinical Remission for Ulcerative Colitis | 5 Participants |
Secondary
Changes in Fecal Microbiome Composition During Dietary Intervention
Changes in fecal microbiome composition at baseline and at weeks 2, 4, 6, and 11 using 16S ribosomal RNA sequencing
Time frame: 11 weeks
Population: Data was not collected. Fecal samples did not achieve quality control requirements in order to analyze data, so this substudy was terminated and analyses were not performed.
Secondary
Changes in Inflammatory Biomarkers, Including C-reactive Protein (CRP), During Dietary Intervention
Number of Participants with a change in C-reactive Protein Levels (inflammatory biomarker) from baseline to 11 weeks.
Time frame: 11 weeks
Population: Of the 15 participants in this trial, 9 participants had available CRP data at the end of the study to evaluate changes in CRP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With Crohn's Disease | Changes in Inflammatory Biomarkers, Including C-reactive Protein (CRP), During Dietary Intervention | 9 Participants |
Secondary
Changes in Inflammatory Biomarkers, Including Fecal Calprotectin (FC), During Dietary Intervention
Number of Participants with a change in fecal calprotectin levels (inflammatory biomarker) from baseline to 11 weeks.
Time frame: 11 weeks
Population: Of the 15 participants in the study, 6 patients had available fecal calprotectin data at 11 weeks for comparison
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With Crohn's Disease | Changes in Inflammatory Biomarkers, Including Fecal Calprotectin (FC), During Dietary Intervention | 6 Participants |
Secondary
Major Biological Processes Gene Ontology Terms Enriched in Downregulated and Upregulated Genes
Description of changes in RNA expression from colonic biopsies from patients with ulcerative colitis from baseline to end of study (11 weeks). Specifically, examined top 10 major Biological Processes Gene Ontology Terms Enriched in Downregulated and Upregulated Genes
Time frame: 11 weeks
Population: Outcome measure is descriptive. Of the 15 participants in this trial, 4 participants with ulcerative colitis had available colon biopsies at baseline and 11 weeks to examine changes in RNA expression in the colon. For all 4 participants, the 10 highest scoring Gene Ontology terms for biological processes associated with upregulated and downregulated genes were presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Crohn's Disease | Major Biological Processes Gene Ontology Terms Enriched in Downregulated and Upregulated Genes | 10 Enriched Gene Ontology Terms |
Secondary
Number of Participants With Mucosal Healing for Crohn's Disease or Ulcerative Colitis
Number of participants with Crohn's disease or ulcerative colitis who have absence of erosions or ulcers on endoscopy or imaging
Time frame: 11 weeks
Population: Of the 15 participants in this study, 7 had available followup endoscopic data available for assessment of mucosal healing.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With Crohn's Disease | Number of Participants With Mucosal Healing for Crohn's Disease or Ulcerative Colitis | 7 Participants |