Obesity, Iron Regulation and Colorectal Cancer Risk

Obesity Clinical Trial

Official title:

Obesity, Iron Regulation and Colorectal Cancer Risk

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03548948
• Other study ID #: 2014-0721
• Status: Completed
• Phase: N/A
• Start date: July 15, 2015
• Est. completion date: June 30, 2019

Study information

• Verified date: September 2019
• Source: University of Illinois at Chicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: June 30, 2019
• Est. primary completion date: November 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 55 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Colon Inflammation
• Diet Modification
• Inflammation
• Iron Malabsorption
• Malabsorption Syndromes
• Obesity

Intervention

Other:
• High heme iron diet
A "Typical American" diet with "high" heme/non-heme iron" (18 mg total). Diet is isocaloric and has a macronutrient composition of total fat 35%, carbohydrates 50%, protein 15% of calories and fiber 9g/1000 calories. Subjects consumes the diet for 3 weeks with a minimum 3 week washout before the next diet.
• Low iron diet
A "Typical American" diet with "low" heme/non-heme iron" (8 mg total). Diet is isocaloric and has a macronutrient composition of total fat 35%, carbohydrates 50%, protein 15% of calories and fiber 9g/1000 calories. Subjects consumes the diet for 3 weeks with a minimum 3 week washout before the next diet.
• Plant-based high non-heme iron diet
A plant-based diet with "high" non-heme iron" (18 mg total). Diet is isocaloric and has a macronutrient composition of total fat 35%, carbohydrates 50%, protein 15% of calories and fiber 9g/1000 calories. Subjects consumes the diet for 3 weeks with a minimum 3 week washout before the next diet.

Locations

Country	Name	City	State
United States	University of Illinois at Chicago	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
University of Illinois at Chicago	American Cancer Society, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in colonic inflammation	Fecal calprotectin, a proxy for colon tissue inflammation, will be measured from stool an calprotectin immunoassay	Baseline and post-diet (day 22) for each of the three 3-week diets
Secondary	Change in systemic inflammation	Circulating C-reactive protein, Interleukin-6 (IL-6) and Tumor necrosis factor-alpha (TNF-a) will be measured from serum using immunoassays.	Baseline and post-diet (day 22) for each of the three 3-week diets
Secondary	Change in stool microbial community profile at the phylum and genus level	Stool samples to analyze the composition of the microbiota, extracted bacterial genomic DNA will be used as a template for polymerase chain reactions targeting the V4 variable regions of the 16S ribosomal ribonucleic acid gene. Amplicons generated from polymerase chain reaction will be run on the Illumina MiSeq sequencing platform to profile microbial communities at the phylum and genus level.	Baseline and post-diet (day 22) for each of the three 3-week diets
Secondary	Change in serum hepcidin	Serum hepcidin will be measured using an immunoassay	Baseline and post-diet (day 22) for each of the three 3-week diets