Clinical trial NCT03548948: Obesity, Iron Regulation and Colorectal Cancer Risk
Official title: Obesity, Iron Regulation and Colorectal Cancer Risk
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Colon Inflammation
Iron Malabsorption
Obesity
Diet Modification
Lead sponsor: University of Illinois at Chicago
Sponsor class: OTHER
Collaborators: name: American Cancer Society, Inc.
First posted: 2018-06-07
Enrollment: 17
Sex: FEMALE
Minimum age (years): 55
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 1. Typical American Diet with "high" heme/non-heme iron (16 mg)
2. Typical American Diet with "low" iron (8 mg)
3. Plant-based Diet with "high" non-heme iron (16 mg)
Primary purpose: OTHER

Brief summary: Obesity is an independent risk factor for colorectal cancer (CRC) although the underlying mechanisms have not been elucidated. Dietary nutrients play a key role in both the prevention and promotion of CRC. While iron is an essential nutrient, excess iron is associated with carcinogenesis. Unlike the systemic compartment, the intestinal lumen lacks an efficient system to regulate iron. In conditions when dietary iron malabsorption and intestinal inflammation co-exist, greater luminal iron is associated with increased intestinal inflammation and a shift in the gut microbiota to more pro-inflammatory strains. However, treatments designed to reduce luminal, including diet restriction and chelation, are associated with lower intestinal inflammation and the colonization of protective gut microbes. Obesity is associated with inflammation-induced, hepcidin-mediated, iron metabolism dysfunction characterized by iron deficiency and dietary iron malabsorption. Obesity is also linked to intestinal inflammation. Currently, there is a fundamental gap in understanding how altered iron metabolism impacts CRC risk in obesity.

The investigator's objective is to conduct a crossover controlled feeding trial of: 1) a "Typical American" diet with "high" heme/non-heme iron", 2) a "Typical American" diet with "low" iron, and 3) a Mediterranean diet with "high" non heme iron and examine effects on colonic and systemic inflammation and the gut microbiome.


Eligibility criteria: Inclusion Criteria:

* Self-identify as Hispanic, African American, or Caucasian.
* Meet body mass index (BMI \> = 30.0 kg/m2) and C-reactive protein (CRP) criteria (\> 2.0 mg/dl)
* Post-menopausal (no menstruation in the past 12 months)
* Weight stable (\< 3% weight change in the past 3 months)
* Non-smoker
* No major medical problems
* Have a working phone
* No known allergies, intolerance, medical, secular or religious dietary restrictions

Exclusion Criteria:

* Chronic constipation (less than three stools per week for several months)
* History or intestinal cancer, inflammatory bowel disease, celiac disease, or malabsorptive bariatric surgery
* Previous intestinal surgery
* H pylori infection or taking H2 blockers (e.g., Zantac, Pepcid) /antacids (e.g., Rolaids) more than 3 times per week
* Significant blood loss or blood donation in past 3 months
* Active gastrointestinal bleed
* Any surgery in the past 3 months
* Hemochromatosis
* Sickle cell disease
* Hereditary polyposis
* Rheumatoid arthritis
* Type I or Type II diabetes
* Smoker
* Antibiotic use in the past 2 months
* Excessive alcohol consumption \[\> 2 standard alcoholic drinks (12 ounces of beer, 5 ounces of wine, 1 shot of hard liquor) per day\]
* Aspirin use \>81 mg/day OR \>325 mg/every other day
* Regularly taking probiotics, fiber supplements, Orlistat (over the counter brand name: Alli), or steroids (inhaled or oral)

Primary outcomes:
measure: Change in colonic inflammation
timeFrame: Baseline and post-diet (day 22) for each of the three 3-week diets
Secondary outcomes:
measure: Change in systemic inflammation
timeFrame: Baseline and post-diet (day 22) for each of the three 3-week diets
measure: Change in stool microbial community profile at the phylum and genus level
timeFrame: Baseline and post-diet (day 22) for each of the three 3-week diets
measure: Change in serum hepcidin
timeFrame: Baseline and post-diet (day 22) for each of the three 3-week diets
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
Study officials:
affiliation: University of Illinois at Chicago
name: Lisa Tussing-Humphreys, PhD, MS, RD
role: PRINCIPAL_INVESTIGATOR
References: