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Completed

NCT Number: NCT03548948

Obesity, Iron Regulation and Colorectal Cancer Risk

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.

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Key information

Conditions

Colon Inflammation Body Weight Colitis Colonic Diseases Diet Modification Digestive System Diseases Gastroenteritis Gastrointestinal Diseases Intestinal Diseases Iron Malabsorption Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

55 year–70 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

University of Illinois at Chicago

Chicago, Illinois, 60608, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

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.

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.

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.

Primary outcomes

  1. Change in colonic inflammation

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

    Fecal calprotectin, a proxy for colon tissue inflammation, will be measured from stool an calprotectin immunoassay

Secondary outcomes

  1. Change in systemic inflammation

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

    Circulating C-reactive protein, Interleukin-6 (IL-6) and Tumor necrosis factor-alpha (TNF-a) will be measured from serum using immunoassays.

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

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

    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.

  3. Change in serum hepcidin

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

    Serum hepcidin will be measured using an immunoassay

Sponsors and collaborators

Lead sponsor

University of Illinois at Chicago

Other

Collaborators

  • American Cancer Society, Inc.

Registry information

Important dates

Study start
2015
Primary completion
2018
Study completion
2019
First posted
Jun 7, 2018
Registry last updated
Sep 27, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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