A Phase 2 interventional study of Sucralose and Placebo in Healthy Volunteers and Overweight, sponsored by National Institute on Alcohol Abuse and Alcoholism (NIAAA). Recruiting at 1 site in United States. Open to female participants aged 18 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-01.
Sponsored by National Institute on Alcohol Abuse and Alcoholism (NIAAA) · Phase 2, Interventional, and Other
Background:
Artificial sweeteners like sucralose are found in many foods and drinks. Sucralose might affect hormones and cause health changes.
Objective:
To see if sucralose changes how medicines are absorbed and processed, how hormones are secreted, gut bacteria, and how fat cells are metabolized.
Eligibility:
People ages 18-60 who:
Design:
Participants will be screened with:
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:
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.
Background:
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.
Aims:
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
Methods:
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:
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.
Age: between 18 and 60 years
4 weeks
8. Able and willing to avoid eating grapefruit, parsnips, celery, drinking grapefruit juice or sodas containing quinine (e.g. tonic water) during the study
9. Able and willing to collect stool specimens
10. Able and willing to consume digoxin and midazolam during study visits
EXCLUSION CRITERIA:
Participants will receive sucralose capsules (approximately 4mg/kg/day) by mouth for 28 days.
Other: Sucralose
Participants will receive placebo capsules by mouth for 28 days.
Other: Placebo
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 capsules will be taken orally 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.
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.
Time frame: 28 days
To investigate the effects of sucralose on glucose metabolism and incretin secretion, lipid metabolism, and intestinal microbiome
We also aim to determine if consumption of approximately 4mg/kg sucralose over a 28-day period leads to: 1)changes in glycemia and glucose stimulated secretion of GLP-1 and other gut hormones during an oral glucose tolerance test (OGTT) 2)changes in lipid metabolism (in vitro (adipose tissue) and in vivo (fasting and during OGTT) 3)alterations in the intestinal microflora
Time frame: 28 days
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National Institute on Alcohol Abuse and Alcoholism (NIAAA)