Interactions of Human Gut Microbiota With Intestinal Sweet Taste Receptors

NCT ID: NCT03032640

Last Updated: 2023-02-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

102 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-01-26

Study Completion Date

2022-10-18

Brief Summary

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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.

Detailed Description

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Conditions

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Obesity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Group 1- Healthy Lean subjects

Group 1 will receive Sodium Saccharin 200mg capsule, 2x/day, Day 1-14

Group Type ACTIVE_COMPARATOR

Oral Glucose Tolerance Test (OGTT)

Intervention Type OTHER

Once we test the fasting plasma glucose (after an overnight fast), subject will receive a 75g glucose beverage they will have to drink within 5 minutes. Then after drinking the beverage, 8 blood samples will be collected through the IV catheter, over the next 3 hours.

Assessment of dietary compliance

Intervention Type OTHER

Assessment of consumption of non-caloric artificial sweeteners

Stool sampling

Intervention Type OTHER

Subjects will provide a stool sample.

Sodium Saccharin

Intervention Type OTHER

Subjects in group 1 and group 3 will be provided with sodium saccharin.

Group 2- Healthy Lean subjects

Group 2 will receive Placebo 500mg capsule, 2x/day, Day 1-14

Group Type ACTIVE_COMPARATOR

Oral Glucose Tolerance Test (OGTT)

Intervention Type OTHER

Once we test the fasting plasma glucose (after an overnight fast), subject will receive a 75g glucose beverage they will have to drink within 5 minutes. Then after drinking the beverage, 8 blood samples will be collected through the IV catheter, over the next 3 hours.

Assessment of dietary compliance

Intervention Type OTHER

Assessment of consumption of non-caloric artificial sweeteners

Stool sampling

Intervention Type OTHER

Subjects will provide a stool sample.

Placebo

Intervention Type OTHER

Subjects in group 2 will be provided with placebo.

Group 3- Healthy Lean subjects

Group 3 will receive Sodium Saccharin 200mg + lactisole 335mg capsule, 2x/day, Day 1-14

Group Type ACTIVE_COMPARATOR

Oral Glucose Tolerance Test (OGTT)

Intervention Type OTHER

Once we test the fasting plasma glucose (after an overnight fast), subject will receive a 75g glucose beverage they will have to drink within 5 minutes. Then after drinking the beverage, 8 blood samples will be collected through the IV catheter, over the next 3 hours.

Assessment of dietary compliance

Intervention Type OTHER

Assessment of consumption of non-caloric artificial sweeteners

Stool sampling

Intervention Type OTHER

Subjects will provide a stool sample.

Sodium Saccharin

Intervention Type OTHER

Subjects in group 1 and group 3 will be provided with sodium saccharin.

Lactisole

Intervention Type OTHER

Subjects in group 3 and group 4 will be provided with lactisole.

Group 4- Healthy Lean subjects

Group 4 will receive Lactisole 335mg capsule, 2x/day, Day 1-14

Group Type ACTIVE_COMPARATOR

Oral Glucose Tolerance Test (OGTT)

Intervention Type OTHER

Once we test the fasting plasma glucose (after an overnight fast), subject will receive a 75g glucose beverage they will have to drink within 5 minutes. Then after drinking the beverage, 8 blood samples will be collected through the IV catheter, over the next 3 hours.

Assessment of dietary compliance

Intervention Type OTHER

Assessment of consumption of non-caloric artificial sweeteners

Stool sampling

Intervention Type OTHER

Subjects will provide a stool sample.

Lactisole

Intervention Type OTHER

Subjects in group 3 and group 4 will be provided with lactisole.

Interventions

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Oral Glucose Tolerance Test (OGTT)

Once we test the fasting plasma glucose (after an overnight fast), subject will receive a 75g glucose beverage they will have to drink within 5 minutes. Then after drinking the beverage, 8 blood samples will be collected through the IV catheter, over the next 3 hours.

Intervention Type OTHER

Assessment of dietary compliance

Assessment of consumption of non-caloric artificial sweeteners

Intervention Type OTHER

Stool sampling

Subjects will provide a stool sample.

Intervention Type OTHER

Sodium Saccharin

Subjects in group 1 and group 3 will be provided with sodium saccharin.

Intervention Type OTHER

Placebo

Subjects in group 2 will be provided with placebo.

Intervention Type OTHER

Lactisole

Subjects in group 3 and group 4 will be provided with lactisole.

Intervention Type OTHER

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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AdventHealth Translational Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Richard Pratley, MD

Role: PRINCIPAL_INVESTIGATOR

Translational Research Institute for Metabolism and Diabetes

Locations

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Translational Research Institute for Metabolism and Diabetes

Orlando, Florida, United States

Site Status

Countries

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United States

References

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Swithers SE. Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends Endocrinol Metab. 2013 Sep;24(9):431-41. doi: 10.1016/j.tem.2013.05.005. Epub 2013 Jul 10.

Reference Type BACKGROUND
PMID: 23850261 (View on PubMed)

Tilg H, Kaser A. Gut microbiome, obesity, and metabolic dysfunction. J Clin Invest. 2011 Jun;121(6):2126-32. doi: 10.1172/JCI58109. Epub 2011 Jun 1.

Reference Type BACKGROUND
PMID: 21633181 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25231862 (View on PubMed)

Saccharin and its salts. IARC Monogr Eval Carcinog Risks Hum. 1999;73:517-624. No abstract available.

Reference Type BACKGROUND
PMID: 10804968 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7330898 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7191585 (View on PubMed)

Renwick AG. The metabolism of intense sweeteners. Xenobiotica. 1986 Oct-Nov;16(10-11):1057-71. doi: 10.3109/00498258609038983.

Reference Type BACKGROUND
PMID: 3541395 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6353664 (View on PubMed)

Sweatman TW, Renwick AG, Burgess CD. The pharmacokinetics of saccharin in man. Xenobiotica. 1981 Aug;11(8):531-40. doi: 10.3109/00498258109045864.

Reference Type BACKGROUND
PMID: 7303723 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3891556 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8266711 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12677645 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33431052 (View on PubMed)

Related Links

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http://www.tri-md.org

Website for Translational Research Institute for Metabolism and Diabetes

Other Identifiers

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TRIMDFH 982524

Identifier Type: -

Identifier Source: org_study_id

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