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Functional Research of Emulsifiers in Humans (FRESH)

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ClinicalTrials.gov Identifier: NCT03440229
Recruitment Status : Active, not recruiting
First Posted : February 21, 2018
Last Update Posted : February 21, 2019
Sponsor:
Collaborators:
Georgia State University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
James Lewis, University of Pennsylvania

Brief Summary:
A randomized double-blind study of the effect of carboxymethylcellulose (CMC) on stool microbiota composition, microbiota localization, and metabolic parameters in healthy subjects. It includes a 11-day in-patient stay, randomization to an emulsifier-free group or a CMC group with the same diet except baked goods/sorbet with added CMC at 15g/person/day.

Condition or disease Intervention/treatment Phase
Healthy Other: Emulsifier-containing diet Not Applicable

Detailed Description:

This is a randomized double-blind, controlled feeding experiment examining the effect of CMC on the stool microbiota composition, gene expression, and microbiota localization with respect to the epithelium. In addition, the investigators will assess the impact of CMC exposure in the diet on markers of metabolic syndrome including response to oral glucose tolerance testing and other plasma metabolite measurements.

Sixteen healthy volunteers will be recruited for a 11-day in-patient study. All participants will receive 3 full days of freshly prepared emulsifier-free food to begin the study. This will be called the "washout period". Participants will then be randomized into an "emulsifier-free" arm and a "CMC" arm in a 1:1 ratio.

Both arms will continue the same diet except that the "CMC" arm's brownie and sorbet will have CMC added to achieve a level of 15 gm per person per day consumption. Serial collection of fecal, plasma, urine and mucosal biopsy samples will be performed to investigate the extent to which CMC consumption by humans impacts the gut microbiota and its interaction with the host parameters related to inflammation and metabolism. Participants will have daily urine and stool collections. Sigmoidoscopies and glucose tolerance testing will be completed on day 1and 11. Blood samples are collected on days 1-4, 8, 10, and 11.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: This is a randomized double-blind controlled feeding experiment.
Primary Purpose: Other
Official Title: Functional Research of Emulsifiers in Humans
Actual Study Start Date : April 6, 2018
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
No Intervention: Emuslfier-free diet
This is western style diet prepared without any emulsifiers. Emulsifier free brownies and sorbet are provided daily.
Experimental: Emulsifier-containing diet
This is a western style diet prepared without any emulsifiers with the exception of the CMC that is included in brownies and sorbet that are provided daily.
Other: Emulsifier-containing diet
CMC is one of many synthetic dietary emulsifiers that are incorporated into a variety of processed foods. We have recently shown that, in mice, consumption of P80 and CMC, alters microbiota composition, have pro-inflammatory potential and promote microbiota encroachment into the colonic mucosa, low-grade inflammation, and metabolic syndrome. However, it is not known whether these compounds have similar effects in humans. We would like to study these effects in the human gut microbiota.
Other Name: Carboxymethylcellulose (CMC)




Primary Outcome Measures :
  1. Distance of nearest bacteria to the epithelium [ Time Frame: 11 days ]
    Measured distance from the epithelium to the nearest bacteria under high powered microscopy


Secondary Outcome Measures :
  1. Change in weight [ Time Frame: 11 days ]
    Comparison of weight change during the study period

  2. Area under glucose concentration curve [ Time Frame: Day 11 ]
    Area under the glucose concentration curves during the oral glucose tolerance test

  3. Area under insulin concentration curve [ Time Frame: Day 11 ]
    Area under the insulin concentration curves during the oral glucose tolerance test

  4. Satiety [ Time Frame: Days 10,11,15, and 16 ]
    Satiety is measured on a 10cm VAS. The mean value will be compared between the groups.

  5. Fecal lipocalin-2 [ Time Frame: Day 11 ]
    Fecal lipocalin-2 by Elisa



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Participant is capable of giving informed consent
  2. Participant is age 18 to 60 years

Exclusion Criteria:

  1. Diagnosis with IBD, celiac disease, or other chronic intestinal disorders. Since we are interested in assessing the impact of diet on the microbiome in the absence of pathologic inflammation, we will exclude participants with chronic intestinal abnormalities.
  2. Baseline bowel frequency less than every 2 days or greater than 3 times daily. Normal bowel frequency is every 3rd day to 3 times per day.20-23 Although unknown, stool frequency could be related to the microbiome composition.24-26 Furthermore, change in diet could alter baseline stool frequency, potentially causing diarrhea, particularly in those with high baseline stool frequency, or severe constipation in those with low stool frequency. To avoid the need for use of antidiarrheal medications or laxatives, which themselves could alter the microbiome composition, these patients will be excluded.
  3. Current smoker. What effect smoking has on the microbiome of the gut is unknown. Furthermore, because our hospital is a smoke-free environment, volunteers will not be able to smoke. Thus, inclusion of smokers would increase the risk of early withdrawal from the study.
  4. Body Mass Index (BMI) <18.5 or >40 at screening. Volunteers with BMI below normal27 will be excluded to prevent inclusion of participants with a subclinical systemic disease that may influence the gut microbiome. Volunteers with severe obesity will be excluded as obesity may be associated with altered gut microbiome composition.
  5. More than two of the criteria for metabolic syndrome:

    • A waist circumference greater than 35 inches (89 centimeters) for women and 40 inches (102 centimeters) for men at screening.
    • A diagnosis of diabetes mellitus or baseline HbA1c > 6.4% or a fasting glucose level of greater than 100mg/dL
    • Systolic blood pressure >130 mmHg or diastolic blood pressure >85 mmHg or treated with medications for hypertension at screening.
    • Fasting triglycerides >149 mg/dl or treated with medications for hypertriglyceridemia
    • Fasting HDL cholesterol <40 mg/dl in men or <50 mg/dl in women or treated with medications for hypercholesterolemia
  6. Known substance abuse disorder or consumption of illicit drugs or alcohol in the 24 hours prior to admission to the Center for Human Phenomic Science (CHPS).
  7. Prior bowel resection surgery other than appendectomy. It is unknown how prior bowel resection surgery may influence the microbiome composition, hence we will exclude these participants.
  8. Contraindication to flexible sigmoidoscopy and biopsies. Patients with suppressed white blood count may be at increased risk of systemic infection following sigmoidoscopy with biopsies. As such, participants with a WBC less than 3,500 or an absolute neutrophil count of less than 1,000 will be excluded. Patients with thrombocytopenia or with a coagulopathy may be at increased risk of bleeding complications after colonoscopic biopsies. As such, patients with a platelet count of less than 100,000 or an INR greater than 1.2 will be excluded from the study.
  9. Estimated GFR<60ml/min/1.73m2 based on measured serum creatinine concentration
  10. Pregnant and lactating women. To avoid any risk to an unborn fetus or new born baby from changing the mother's diet, pregnant and lactating women will be excluded.
  11. Use of antibiotics in the 6 months prior to Visit 2. A small proportion of bacteria may require 6 months to recover after treatment with antibiotics.28
  12. Use of antacids, NSAIDs, or dietary supplements in the week prior to Visit 2. NSAIDs have been associated with C. difficile colitis, although whether this is causative and whether this is mediated through changing the fecal microbiota composition is unknown.29 Antacids could potentially alter the gut microbiota by changing the acid milieu or by altering fecal transit time. For our study purposes, multivitamins will not be considered dietary supplements.
  13. Use of laxatives or anti-diarrhea medications in the two weeks prior to Visit 2.
  14. Use of anticholinergics in the week prior Visit 2.
  15. Use of narcotics in the week prior to Visit 2.
  16. HIV infection, AIDS, or other known conditions resulting in immunosuppression - we will determine this by direct participant query; no formal testing will be done.
  17. Allergies or intolerance to the components of the study diets.
  18. Participant has experienced diarrhea within the two weeks prior to Visit 2. Diarrhea is defined as a change in bowel habits with an increased frequency or loose stools such that the stool could not be lifted with a fork.
  19. Refusal to use a medically accepted method of birth control while participating in this study, such as a barrier method, hormonal contraceptives, implanted birth control devices, permanent methods (such as a vasectomy), and/or abstinence.
  20. Vegans and Vegetarians.
  21. Student or employee of any one of the investigators.
  22. Anyone who cannot receive study payment (ie: visa)
  23. Any condition that the investigator feels may limit the volunteer's ability to complete the study protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03440229


Locations
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United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Georgia State University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Jim Lewis, MD, MSCE University of Pennsylvania

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Responsible Party: James Lewis, Professor of Medicine, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT03440229     History of Changes
Other Study ID Numbers: 828422
R21DK115180 ( U.S. NIH Grant/Contract )
First Posted: February 21, 2018    Key Record Dates
Last Update Posted: February 21, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carboxymethylcellulose Sodium
Laxatives
Gastrointestinal Agents