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Effects of Dietary Fructose on Gut Microbiota and Fecal Metabolites in Obese Men and Postmenopausal Women: A Pilot Study

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ClinicalTrials.gov Identifier: NCT03339245
Recruitment Status : Completed
First Posted : November 13, 2017
Last Update Posted : February 5, 2019
Sponsor:
Collaborators:
Weill Medical College of Cornell University
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Peter Holt, MD, Rockefeller University

Tracking Information
First Submitted Date  ICMJE November 7, 2017
First Posted Date  ICMJE November 13, 2017
Last Update Posted Date February 5, 2019
Actual Study Start Date  ICMJE December 5, 2017
Actual Primary Completion Date October 2, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 13, 2017)
Difference in the distribution of fecal microbiota in each participant [ Time Frame: assessed at Day 16 of each intervention, up to 64 days ]
Difference in the distribution of fecal microbiota in each participant, between the fructose versus glucose supplemented diet arms of the study, as measured at the end of each intervention.
Original Primary Outcome Measures  ICMJE
 (submitted: November 7, 2017)
Difference in the distribution of fecal microbiota in each participant [ Time Frame: Day 16 of each Study Arm (+2 days) ]
Difference in the distribution of fecal microbiota in each participant, between the fructose versus glucose supplemented diet arms of the study, as measured at the end of each intervention.
Change History Complete list of historical versions of study NCT03339245 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of Dietary Fructose on Gut Microbiota and Fecal Metabolites in Obese Men and Postmenopausal Women: A Pilot Study
Official Title  ICMJE Effects of Dietary Fructose on Gut Microbiota and Fecal Metabolites in Obese Men and Postmenopausal Women: A Pilot Study
Brief Summary

Non alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver function tests in the U.S. (Browning, et al., 2004), ranging from steatosis to end-stage liver disease. Fructose ingestion by the American public has steadily increased since the 1980's, and with it increases in NAFLD, fatty liver hepatitis (NASH), diabetes, obesity, and cardiovascular disease. Foods and beverage in the U.S. are typically sweetened with sucrose (50% glucose and 50% fructose) or high fructose corn syrup (45-58% glucose and 42-55% fructose) (Stanhope, et al., 2009). Research into the role that added fructose plays in the emerging chronic health issues is necessary to affect public policy and provide the connection between fructose and the increasing incidence of these co-morbidities.

There is evidence that gut bacteria contribute to a range of human diseases including those of the liver and gastrointestinal tract. Dietary fructose has been suggested to play a role in the development of these diseases and has been shown to alter gut microbes in animals. If the investigators find that dietary fructose alters bacteria in the human gut, this would suggest a potential targetable link between high fructose diet and disease.

Detailed Description

Non- alcoholic fatty liver disease (NAFLD) occurs in 30% of the adult US population (Luther, J., et al., 2015). Eating large amounts of fructose (a dietary sugar) increases liver fat accumulation and worsens NAFLD. In addition, fructose consumption has been shown to greatly increase triglycerides(fat) in the blood after meals, increasing the risk of heart disease,(Stanhope,et al., 2009) insulin resistance and diabetes. Current theories on liver disease caused by consuming fructose focuses on changes in the breakdown of fat by the liver. In experimental animals, fructose feeding changes the bacteria population (microbiota) in the gut, causes NAFLD and NASH, and increases leaking of toxins from the intestine (intestinal permeability) to the blood stream resulting in inflammation.

In humans, fructose consumption rapidly increases liver fat. However, changes in gut microbiota have not been studied. The proposed study will compare the addition of fructose or glucose to the study subjects' usual diet in a crossover design. They will not know which sugar they are receiving.

The Investigators plan to study postmenopausal, moderately obese but healthy women, and moderately obese but healthy men (age 45-70 years) to find out the effect of fructose verses glucose on the bacteria in their stool and inflammation in the bowel. The Investigators hypothesize that adding fructose to the participant's usual diet, compared to glucose, will change stool bacteria composition and the products that the bacteria produce, which may increase intestinal leakage, and increase markers of inflammation in the stool and blood due to this leakage. These changes may contribute to fructose -induced liver disease.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Masking Description:
Double blind
Primary Purpose: Basic Science
Condition  ICMJE
  • Non-Alcoholic Fatty Liver Disease
  • Obesity
Intervention  ICMJE
  • Other: Fructose Solution (75 Grams)
    Fructose given in divided doses at breakfast and dinner.
  • Other: Glucose Solution (75 grams)
    Glucose given in divided doses at breakfast and dinner.
    Other Name: Dextrose
Study Arms  ICMJE
  • Experimental: Glucose, Then Fructose
    Participants first receive Glucose Solution (75 grams) from Day 3 through Day 16 of an inpatient stay with usual diet. After a 2-3 week washout period, they will then receive Fructose Solution (75 Grams) from Day 3 through Day 16 on a second inpatient stay with usual diet.
    Interventions:
    • Other: Fructose Solution (75 Grams)
    • Other: Glucose Solution (75 grams)
  • Experimental: Fructose, Then Glucose
    Participants first receive Fructose Solution (75 grams) from Day 3 through Day 16 of an inpatient stay with usual diet. After a 2-3 week washout period, they will then receive Glucose Solution (75 grams) from Day 3 through Day 16 on a second inpatient stay with usual diet.
    Interventions:
    • Other: Fructose Solution (75 Grams)
    • Other: Glucose Solution (75 grams)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 7, 2017)
10
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE October 2, 2018
Actual Primary Completion Date October 2, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Post menopausal female, last menstrual period at least 24 months ago OR male
  • Age 45-70
  • Willing to consume usual diet with either fructose or glucose added during (2) 16-18 day inpatient stays
  • Willing to consume usual diet during 2 week wash-out period at home
  • BMI 30.0-39.9
  • Willingness not to travel long distances while on study, including wash-out period
  • Willingness not to be exposed to new pets while on study including wash-out period

Exclusion Criteria:

  • Fasting serum triglycerides >200mg/dl
  • Fasting blood glucose >126mg/dl
  • Renal function tests >2x Upper limit of normal
  • Liver Function Tests > 1.5x Upper limit of normal
  • Currently on statins
  • Daily use of a cathartic
  • Broad spectrum antibiotic use within the past 45 days
  • Currently on proton pump inhibitor
  • Currently on insulin or oral hypoglycemic agents
  • Active viral Hepatitis
  • Chronic constipation
  • Inflammatory bowel disease
  • Chronic diarrhea
  • GI resection
  • Any evidence of cardiovascular disease on EKG
  • History of cardiovascular disease such as coronary artery disease, Coronary Artery Bypass Graft, valve replacement, Myocardial Infarction, stroke / Transient Ischemic attack.
  • History of macronutrient malabsorption
  • Current smoker. Stopped < 3 months ago.
  • Daily alcohol intake equal to 1.5 oz of 40 proof alcohol.
  • HIV positive
  • Any medical, psychological or social condition that, in the opinion of the Investigator, would jeopardize the health or well-being of the participant during any study procedures or the integrity of the data
  • Persons taking probiotics
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 45 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03339245
Other Study ID Numbers  ICMJE PHO-0956
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Peter Holt, MD, Rockefeller University
Study Sponsor  ICMJE Rockefeller University
Collaborators  ICMJE
  • Weill Medical College of Cornell University
  • National Institutes of Health (NIH)
Investigators  ICMJE
Principal Investigator: Peter Holt, MD Rockefeller University
PRS Account Rockefeller University
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP