Ulcerative Colitis (Disorder)
Conditions
Brief summary
The purpose of this study is to determine whether consumption of 237 ml of pomegranate juice daily for 8 weeks will: 1. lower inflammation (in the gut as well as generally in the body) and improve your overall quality of life 2. affect the microbes living in the gut (gut microbiota)
Detailed description
the study is aimed at evaluating the effects of pomegranate juice (PomJ) on: 1) gut inflammation (fecal calprotectin and Simple Clinical Colitis Activity Index) and quality of life; 2) circulating inflammatory markers (e.g., hs-CRP, IL-6, IL-10, TNF-a, IL-1b, IL-8, LBP, LPS) and markers of oxidative stress (blood and urine malondialdehyde (MDA)) and 3) gut microbiota composition and functionality (urinary and circulating urolithin metabolites, fecal SCFAs/BAs, blood LBP and LPS, etc.). We will perform a randomized, controlled, 16-week trial to generate preliminary evidence on the effects of PomJ consumption in patients with mild-to-moderate UC. Participants will be randomly assigned to one of two groups: intervention group and delayed start group. The study will involve 2 phases, each lasting for 8 weeks. During Phase 1, the intervention group will consume 237 ml of PomJ daily, while the delayed start group will follow their habitual diet. Data generated from the delayed start group during Phase 1 will serve as the control for the study. During Phase 2, the intervention group will stop consuming PomJ and switch to consuming their habitual diet, while the delayed start group will consume 237 ml of PomJ daily for 8 weeks. Data generated from the intervention group during Phase 2 will serve as a follow-up to explore whether the effects of PomJ consumption persist after consumption is stopped (this will be an exploratory outcome).
Interventions
OTHERpomegranate juice -> habitual diet
237 ml of pomegranate juice for the first 8 weeks -\> habitual diet for the second 8 weeks
OTHERhabitual diet -> pomegranate juice
habitual diet for the first 8 weeks -\> 237 ml of pomegranate juice for the second 8 weeks
Sponsors
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* • Adults ≥ 18 yo * Following a low-polyphenol and fiber diet (\< 3 servings of fruits/vegetables per day) * Mild-to-moderate UC at the time of screening (2 ≤ partial Mayo scores ≤ 5) * Supportive evidence of active inflammation (hsCRP \>1 mg/L, fecal calprotectin \>50 µg/g stool, or abnormal lower endoscopy) in individuals with biopsy-proven UC * Patients on 5-aminosalicylates must be on a stable dose for ≥ 4 weeks prior to screening * Patients on treatment with immunosuppressive therapy (e.g., azathioprine/6-mercaptopurine, methotrexate) must be on stable dose for 8 weeks prior to baseline visit * At the time of baseline visit, patients may be on no more than 20 mg/day of prednisone and 9 mg/day of budesonide MMX * Subjects must read and sign the Institutional Review Board-approved written informed consent prior to the initiation of any study specific procedures or enrollment. A subject will be excluded for any condition that might compromise the ability to give truly informed consent.
Exclusion criteria
* • Non-English speaker * Vegetarian/vegan * Known pomegranate allergy * Documented chronic disease besides UC, including diabetes, renal or liver diseases, metabolic syndrome, active cancer, MI or stroke, history of gastric bypass * Patients with CD, indeterminate/severe to fulminant colitis * History of colectomy or colonic dysplasia * Presence of ileal pouch or ostomy * Evidence of active bacterial or viral gastroenteritis as indicated by positive stool studies for ova & parasites, Clostridium difficile, and stool culture * Recent hospitalizations (within 2 weeks of screening) for UC requiring IV steroids * Presence of the following labs indicative of severe colitis: a. Hemoglobin \< 8.0 g/dl b. Albumin \< 3.0 g/dl * Recent systemic antibiotics use (within 3 months of screening) or active use of anti-diarrheal medications * Taking supplements known to affect metabolism or gut microbiota composition (probiotics, fiber, etc.), unless willing to stop for the study duration * Use of Total Parenteral Nutrition (TPN) * Use of cyclosporine, tacrolimus, or thalidomide within 2 months prior to screening * Taking exogenous hormones (e.g., hormone replacement therapy) * Recent weight fluctuations (\>10% in the last 6 months) * Smoker or living with a smoker * Use of \>20 g of alcohol per day * Unable or unwilling to comply with the study protocol (including unwillingness to avoid watermelon and other lycopene-rich foods for the whole duration of the study) * Unable to provide consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| simple clinical colitis activity index (SCCAI) | At baseline, 8 weeks and 16 weeks | Simple Clinical Colitis Activity Index (SCCAI) includes questions about bowel frequency, urgency of defecation, etc. Measured by the number of points/scores. |
| Fecal calprotectin | At baseline, 8 weeks and 16 weeks | To evaluate effects of PomJ on gut inflammation in patients with mild-to-moderate UC. The primary outcome will be levels of fecal calprotectin (objective measure). Fecal calprotectin levels will be assessed via a commercially available ELISA kit in mcg/g. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biomarkers of inflammation and oxidative stress | At baseline, week 8 and week 16 | Blood interleukin-6 (IL-6) in pg/ml |
| Biomarkers of aging and oxidative stress | At baseline, week 8 and week 16 | Blood TNF-a in pg/ml |
Other
| Measure | Time frame | Description |
|---|---|---|
| Gut-derived metabolites | At baseline, weeks 8 and 16 | Blood urolithin metabolites in micromoles/L |
| Microbial inflammatory components | At baseline, weeks 8 and 16 | Blood lipopolysaccharide in ng/ml |
| Microbial-derived metabolites | At baseline, weeks 8 and 16 | Fecal short-chain fatty acids (SCFAs) in micromoles/g |
| Gut microbiota composition | At baseline, weeks 8 and 16 | The stool specimen will be collected by the participants at home at baseline and week 12 utilizing our Stool Collection Kit as per instructions. Immediately after collection, the specimen will be frozen in a home freezer and delivered in an insulated container to the UCLA Center for Human Nutrition. At UCLA, the specimen will be stored at - 80 ºC. Fecal microbiological analyses. Approximately 1g of the stool will be weighed and dried in a vacuum drying oven (15 in Hg) at 80 ºC for 48 hours, then weighed again to establish the moisture content so that all counts can be corrected to dry weight. From another aliquot of remaining fecal samples, DNA will be extracted using bead beating with a commercial extraction system (DNeasy PowerSoil® DNA Isolation Kit, Qiagen, Valencia, CA). The quality of the DNA samples will be confirmed using a Nanodrop 1000 (Thermo Fisher Scientific, Wilmington, DE). Extracted DNA will be transferred to UCLA Microbiome Core facility for MiSeq sequencing. |
Countries
United States
Contacts
Primary ContactTatiana Diacova, PhD, MS, RDN
Outcome results
None listed