Clinical trial NCT03032640: Interactions of Human Gut Microbiota With Intestinal Sweet Taste Receptors
Official title: Interactions of Human Gut Microbiota With Intestinal Sweet Taste Receptors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Keywords: Glucose
Sweet taste receptors
Artificial sweeteners
Lead sponsor: AdventHealth Translational Research Institute
Sponsor class: OTHER
First posted: 2017-01-26
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to collect data to examine whether short-term consumption of non-caloric artificial sweeteners (NCASs), such as saccharin, can lead to changes in blood sugar levels and in the composition of the bacteria in the large intestine.


Eligibility criteria: Inclusion Criteria:

1. Able to provide written informed consent
2. Age 18-45 years
3. Weight stable (± 3 kg) during the 6 months prior to enrollment
4. BMI ≤ 25 kg/m2
5. Consumption of less than a can of diet beverage or a spoonful of NCASs weekly (or each equivalent from foods) during the past month

Exclusion Criteria:

1. Known coronary artery disease, angina or congestive heart failure
2. Type 1 or Type 2 Diabetes (A1c ≥6.5%)
3. Bleeding disorders
4. Hemoglobin level \< 12.5 g/dL for women; hemoglobin level \< 13.0 g/dL for men
5. Acute or chronic infections
6. Hepatitis and/or cirrhosis
7. Severe asthma or chronic obstructive pulmonary disease
8. Renal insufficiency or nephritis (creatinine \> 1.6 mg/dl)
9. Prior bariatric surgery
10. Inflammatory bowel disease or malabsorption
11. Cancer within the last 3 years (except non-melanoma skin cancer or treated cervical carcinoma in situ)
12. Psychiatric disorders or eating disorders
13. Cushing's disease or syndrome
14. Untreated or inadequately controlled hypo- or hyperthyroidism (abnormal TSH)
15. Active rheumatoid arthritis or other inflammatory rheumatic disorder
16. Pregnant or nursing women
17. Smoking (smoking within the past 3 months)
18. Less than 4 bowel movements per week
19. Known hypersensitivity to saccharin, lactisole or any of its excipients.

    Excluded medications include but are not limited to:
20. Anti-diabetic agents
21. Oral, injected or chronic topical steroids (inhaled steroids for mild asthma are acceptable)
22. Antibiotic use (within the past 3 months)
23. Other drugs known to affect immune or metabolic function
24. Orlistat, phentermine, topiramate or other weight loss or anorectic agents (tricyclic antidepressants, atypical antipsychotics or other psychiatric drugs with effects on body weight)

Primary outcomes:
measure: Blood analyzed by way of NOVA StatStrip Meter and Milliplex Map Kit.
timeFrame: 6 weeks
Secondary outcomes:
measure: Short chain fatty acid analyses
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Translational Research Institute for Metabolism and Diabetes
state: Florida
Study officials:
affiliation: Translational Research Institute for Metabolism and Diabetes
name: Richard Pratley, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, Israeli D, Zmora N, Gilad S, Weinberger A, Kuperman Y, Harmelin A, Kolodkin-Gal I, Shapiro H, Halpern Z, Segal E, Elinav E. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014 Oct 9;514(7521):181-6. doi: 10.1038/nature13793. Epub 2014 Sep 17.
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citation: Pantarotto C, Salmona M, Garattini S. Plasma kinetics and urinary elimination of saccharin in man. Toxicol Lett. 1981 Dec;9(4):367-71. doi: 10.1016/0378-4274(81)90012-6.
citation: Sweatman TW, Renwick AG. The tissue distribution and pharmacokinetics of saccharin in the rat. Toxicol Appl Pharmacol. 1980 Aug;55(1):18-31. doi: 10.1016/0041-008x(80)90215-x. No abstract available.
citation: Renwick AG. The metabolism of intense sweeteners. Xenobiotica. 1986 Oct-Nov;16(10-11):1057-71. doi: 10.3109/00498258609038983.
citation: Arnold DL, Krewski D, Munro IC. Saccharin: a toxicological and historical perspective. Toxicology. 1983 Jul-Aug;27(3-4):179-256. doi: 10.1016/0300-483x(83)90021-5.
citation: Sweatman TW, Renwick AG, Burgess CD. The pharmacokinetics of saccharin in man. Xenobiotica. 1981 Aug;11(8):531-40. doi: 10.3109/00498258109045864.
citation: Renwick AG. The disposition of saccharin in animals and man--a review. Food Chem Toxicol. 1985 Apr-May;23(4-5):429-35. doi: 10.1016/0278-6915(85)90136-x.
citation: Evaluation of certain food additives and contaminants. Forty-first report of the Joint FAO/WHO Expert Committee on Food Additives. World Health Organ Tech Rep Ser. 1993;837:1-53. No abstract available.
citation: Food and Agriculture Organization World Health Organization. Evaluation of certain food additives. Fifty-ninth report of the Joint FAO/WHO Expert Committee on Food Additives. World Health Organ Tech Rep Ser. 2002;913:i-viii, 1-153, back cover.
citation: Serrano J, Smith KR, Crouch AL, Sharma V, Yi F, Vargova V, LaMoia TE, Dupont LM, Serna V, Tang F, Gomes-Dias L, Blakeslee JJ, Hatzakis E, Peterson SN, Anderson M, Pratley RE, Kyriazis GA. High-dose saccharin supplementation does not induce gut microbiota changes or glucose intolerance in healthy humans and mice. Microbiome. 2021 Jan 12;9(1):11. doi: 10.1186/s40168-020-00976-w.