Obesity, Iron Regulation and Colorectal Cancer Risk

NCT03548948 | Completed

• 1 other identifier: 2014-0721
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Colon Inflammation; Iron Malabsorption; Obesity; Diet Modification

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Change in systemic inflammation

  Baseline and post-diet (day 22) for each of the three 3-week diets

• Change in stool microbial community profile at the phylum and genus level

  Baseline and post-diet (day 22) for each of the three 3-week diets

• Change in serum hepcidin

  Baseline and post-diet (day 22) for each of the three 3-week diets

Study Arms (3)

High heme iron diet

OTHER

Other: High heme iron diet

Low iron diet

OTHER

Other: Low iron diet

Plant-based high non-heme iron diet

OTHER

Other: Plant-based high non-heme iron diet

Interventions

High heme iron diet OTHER

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.

High heme iron diet

Low iron diet OTHER

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.

Low iron diet

Plant-based high non-heme iron diet OTHER

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.

Plant-based high non-heme iron diet

Eligibility Criteria

• Age: 55 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 \[\> 2 standard alcoholic drinks (12 ounces of beer, 5 ounces of wine, 1 shot of hard liquor) per day\]

Sponsors & Collaborators

• University of Illinois at Chicago: lead
• American Cancer Society, Inc.: collaborator

Study Sites (1)

University of Illinois at Chicago

Chicago, Illinois, 60608, United States

Location

MeSH Terms

Conditions

Colitis; Obesity

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Lisa Tussing-Humphreys, PhD, MS, RD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: 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)

Study Record Dates

• First Submitted: May 7, 2018
• First Posted: June 7, 2018
• Study Start: July 15, 2015
• Primary Completion: November 1, 2018
• Study Completion: June 30, 2019
• Last Updated: September 27, 2019

Record last verified: 2019-09

Locations

US (1)