Functional Research of Emulsifiers in Humans

NCT03440229 | Completed Results

• 2 other identifiers: 828422R21DK115180
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Distance of Nearest Bacteria to the Epithelium

  Measured distance from the epithelium to the nearest bacteria under high powered microscopy; The measurements were taken on the last day of the diet intervention. An average of 3 measurements was taken.

  last day of inpatient stay (either day 17 for the 3 participants with a 17 day inpatient stay or day 11 for the 13 participants with an 11 day inpatient stay.)

Secondary Outcomes (5)

• Change in Weight

  For 3 participants with a 17 day stay, weight was measured on Day 4 and Day 17 of the inpatient stay. For 13 participants with an 11 day stay, weight was measured on Day 1 and Day 11 of the inpatient stay.

• Area Under Glucose Concentration Curve

  For 3 participants with a 17 day stay, area under the glucose curve was measured on days 4 and 17 of the inpatient stay . For 13 participanst with an 11 day stay, area under the glucose curve was measured on days 1 and Day 11 of the inpatient stay.

• Area Under Insulin Concentration Curve

  For 3 pts. with 17 day stays, area under the curve was measured on days 4 and 17 of the inpatient stay. For 13 pts. with 11 day stays, area under the curve was measured on days 1 and Day 11 of the inpatient stay.

• Visual Analog Scale Measurements - Satiety/Hunger - Change From Baseline

  Measured at end of inpatient stay (Day 17 for 3 participants and Day 11 for 13 participants) comparing it to the study start (prior to diet intervention; either day 4 for the 3 participants or day 1 for 13 participants.

• Fecal Lipocalin-2

  For the 3 participants with a 17 day inpatiet stay, this was measured on Day 17. For the 13 participants with an 11 day stay, this was measured on Day 11

Study Arms (2)

Emuslfier-free diet

NO INTERVENTION

This is western style diet prepared without any emulsifiers. Emulsifier free brownies and sorbet are provided daily.

Emulsifier-containing diet

EXPERIMENTAL

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

Interventions

Emulsifier-containing diet OTHER

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.

Also known as: Carboxymethylcellulose (CMC)

Emulsifier-containing diet

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant is capable of giving informed consent
• Participant is age 18 to 60 years

You may not qualify if:

• Diagnosis with Inflammatory Bowel Disease (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.
• 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.
• 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
• 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).
• 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.
• 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 white blood cell (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 international normalized ratio (INR) greater than 1.2 will be excluded from the study.
• Estimated glomerular filtration rate (GFR)\<60ml/min/1.73m2 based on measured serum creatinine concentration
• 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.
• 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
• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead
• Georgia State University: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

• Doucet E, Pomerleau M, Harper ME. Fasting and postprandial total ghrelin remain unchanged after short-term energy restriction. J Clin Endocrinol Metab. 2004 Apr;89(4):1727-32. doi: 10.1210/jc.2003-031459.

  PMID: 15070937 BACKGROUND

• Chassaing B, Compher C, Bonhomme B, Liu Q, Tian Y, Walters W, Nessel L, Delaroque C, Hao F, Gershuni V, Chau L, Ni J, Bewtra M, Albenberg L, Bretin A, McKeever L, Ley RE, Patterson AD, Wu GD, Gewirtz AT, Lewis JD. Randomized Controlled-Feeding Study of Dietary Emulsifier Carboxymethylcellulose Reveals Detrimental Impacts on the Gut Microbiota and Metabolome. Gastroenterology. 2022 Mar;162(3):743-756. doi: 10.1053/j.gastro.2021.11.006. Epub 2021 Nov 11.

  PMID: 34774538 DERIVED

MeSH Terms

Interventions

Carboxymethylcellulose Sodium

Intervention Hierarchy (Ancestors)

Methylcellulose; Cellulose; Glucans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Dr. James D. Lewis
• Organization: University of Pennsylvania

james.lewis@pennmedicine.upenn.edu

215-573-5137

Study Officials

• Jim Lewis, MD, MSCE

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a randomized double-blind controlled feeding experiment.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: February 5, 2018
• First Posted: February 22, 2018
• Study Start: April 6, 2018
• Primary Completion: May 13, 2019
• Study Completion: May 13, 2019
• Last Updated: October 19, 2021
• Results First Posted: September 16, 2021

Record last verified: 2021-09

Locations

US (1)