Effects of Sucralose on Drug Absorption and Metabolism (The SweetMeds Study)
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|ClinicalTrials.gov Identifier: NCT03407079|
Recruitment Status : Recruiting
First Posted : January 23, 2018
Last Update Posted : November 12, 2018
Artificial sweeteners like sucralose are found in many foods and drinks. Sucralose might affect hormones and cause health changes.
To see if sucralose changes how medicines are absorbed and processed, how hormones are secreted, gut bacteria, and how fat cells are metabolized.
People ages 18-60 who:
- Are black or Hispanic
- Weigh more than 110 pounds
- Have a body mass index of 25-40
- Do not have a condition that requires drug treatment
Participants will be screened with:
- Medical history
- Physical exam
- Blood, heart, and urine tests
Participants must not eat or drink anything with artificial sweeteners throughout the study.
Over 7 days, Participants will answer questions, and give daily urine samples and 1 stool sample. Participants will repeat these throughout the study.
Overnight Visit 1: participants will fast starting the night before. They will get breakfast at the visit. The visit includes:
- An IV will be placed in the arm. Participants will get 2 tablets of medicines. Blood will be drawn several times over 24 hours.
- A piece of fat tissue may be taken from the abdomen (biopsy).
- Participants will have a sweet drink. Blood samples will be taken over 2 hours.
Then participants will be randomly assigned to take either a sucralose capsule or placebo. They will take it twice a day for 2 weeks. They will complete two 24-hour food diaries.
Overnight Visit 2 repeats Visit 1 except the biopsy.
Then participants will take the capsules for another 2 weeks.
Overnight Visit 3 repeats Visit 1.
Participants may be contacted by phone within 4 weeks after they finish.
|Condition or disease||Intervention/treatment||Phase|
|Healthy Volunteers Overweight||Other: Sucralose Other: Placebo||Phase 2|
Consumption of non-nutritive sweeteners (NNS) has dramatically increased worldwide and is more prevalent in women than men. Similarly, obesity rates have continued to rise, most notably in minorities. Since NNS consumption has been linked to obesity, we propose studying NNS effects specifically in minority women.
NNS are frequently consumed in combination with prescription medications. This necessitates the study of possible NNS-drug interactions. The hypothesis that NNS may affect drug absorption and metabolism is based on a rodent study. In 2008, Abou-Donia et al reported that sucralose increased the activity of P-glycoprotein (P-gp), a membrane transporter involved in absorption and distribution of a wide range of pharmacologic compounds, and CYP3A, a cytochrome P-450 enzyme important to the first-pass metabolism of many drugs.
So far, NNS effects in clinical studies were mostly observed after acute (one time) or short term exposure. For example, we and others found increased incretin and insulin concentrations in response to sucralose alone or in combination with acesulfame-potassium prior to a glucose load. The effects were most pronounced in obese African American women. We also found upregulation of inflammatory cytokines in subcutaneous fat biopsies of obese individuals who reported consumption of NNS compared to non-consumers. Whether these hormonal and tissue responses persist after prolonged exposure needs to be investigated. NNS have also been shown to influence the microbial composition of the oral cavity and the gut. However, most data were generated in mice and do not exist in humans.
Primary Aim: To determine the effects of sucralose (4 mg/kg/day) administered to overweight and obese minority women for 28 days on drug metabolism using digoxin and midazolam as probes for P-glycoprotein and CYP3A, respectively.
Secondary Aims: To investigate the effects of sucralose on
- glucose metabolism and incretin secretion
- lipid metabolism
- intestinal microflora
The study consists of 3 periods. In the first period (run-in, 7 days), participants will be instructed to avoid all NNS (including NNS in cosmetics or health care products). During the second and third periods (14 days each), participants will be randomized to consume either sucralose containing capsules (4 mg/kg/day) or placebo. At the end of each period, the following measurements will be obtained during an overnight hospitalization:
- Serial measurements of plasma concentrations of midazolam and digoxin for 24 hours following a single oral dose of each drug
- Frequently sampled 2-hour oral glucose tolerance test (OGTT) to measure glucose, insulin, C-peptide, GLP-1, and other gut hormones.
At the end of P1 (run-in, no intervention) and after P3 (sucralose exposure x 4 weeks), subcutaneous fat biopsies will be performed. Stool samples will be obtained throughout.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||150 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Effects of Sucralose on Drug Absorption and Metabolism (The SweetMeds Study)|
|Actual Study Start Date :||April 5, 2018|
|Estimated Primary Completion Date :||September 12, 2020|
|Estimated Study Completion Date :||August 1, 2021|
Experimental: Study Arm 1
Participants will receive sucralose capsules (approximately 4mg/kg/day) by mouth for 28 days.
Sucralose is an organochlorine and is approximately 600 times sweeter than sucrose. Participants will receive sucralose (approximately 4mg/kg/day) or placebo by mouth in a capsule for 28 days. This dose corresponds to the amount of sucralose contained in approximately 3 or 4 twelve ounce cans of commercially-available diet soda for a 70 kg adult.
Placebo Comparator: Study Arm 2
Participants will receive placebo capsules by mouth for 28 days.
- To explore the effects of sucralose (approx 4 mg/kg x 28 days) on pharmacokinetics of digoxin and midazolam, which are representative examples of P-gp and CYP3A dependent medications. [ Time Frame: 28 days ]
- Glucose metabolism and incretin secretion [ Time Frame: 28 days ]
- Lipid metabolism [ Time Frame: 28 days ]
- Intestinal microbiome [ Time Frame: 28 days ]
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): NCT03407079
|Contact: Kristina I Rother, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Kristina I Rother, M.D.||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|