Effects of Sucralose on Drug Absorption and Metabolism (The SweetMeds Study)

NCT03407079 | Recruiting Phase 2

• 2 other identifiers: 18004718-AA-0047
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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:

• 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 Design: 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.

Conditions

Healthy Volunteers; Overweight

Keywords

Drug Metabolism; Artificial Sweetener; P-Glycoprotein; Cytochrome P450; Microbiome

Outcome Measures

Primary Outcomes (1)

• 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.

  28 days

Secondary Outcomes (1)

• To investigate the effects of sucralose on glucose metabolism and incretin secretion, lipid metabolism, and intestinal microbiome

  28 days

Study Arms (2)

Study Arm 1

EXPERIMENTAL

Participants will receive sucralose capsules (approximately 4mg/kg/day) by mouth for 28 days.

Other: Sucralose

Study Arm 2

PLACEBO COMPARATOR

Participants will receive placebo capsules by mouth for 28 days.

Other: Placebo

Interventions

Sucralose OTHER

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.

Study Arm 1

Placebo OTHER

Placebo capsules will be taken orally for 28 days

Study Arm 2

Eligibility Criteria

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

You may qualify if:

• Age: between 18 and 60 years
• Female adults who self-identify as Hispanic and/or Black
• Body weight greater than 50 kg (110 lb)
• Body mass index between 25 kg/m\^2 and 40 kg/m\^2
• Consumption of less than or equal to one 12-ounce beverage sweetened with NNS per month or food equivalent
• Healthy with no known active medical condition or illness that requires drug treatment
• Able and willing to consume approximately 4 mg/kg sucralose daily or placebo in form of capsules for
• weeks
• \. Able and willing to avoid eating grapefruit, parsnips, celery, drinking grapefruit juice or sodas containing quinine (e.g. tonic water) during the study
• \. Able and willing to collect stool specimens
• \. Able and willing to consume digoxin and midazolam during study visits

You may not qualify if:

• Current use of prescription or non-prescription medication(s), herbal medications and oral contraceptives are also excluded. Certain exceptions are permitted, including vitamins. Other medications may be permitted at the discretion of the investigators.
• Diabetes (fasting blood glucose of 126 mg/dl or higher, or 2-hour blood glucose of 200 or higher on OGTT)
• Taken medications that affect blood sugar in the past 3 months or that include antibiotics
• GI history, at the discretion of the investigators
• Known allergy, sensitivity, or other contraindication to study procedures
• ALT or AST more than 1.5 times the upper limit of normal
• Abnormal thyroid function or abnormal serum electrolytes \& minerals (specifically potassium, calcium, and magnesium)
• Narrow angle glaucoma or untreated open angle glaucoma
• Regular use of alcohol (more than 1 drink per day) or drug use
• History of cardiac abnormalities, especially arrhythmia
• Unable or unwilling to cooperate with study procedures
• Psychiatric or cognitive disorder that will, in the opinion of the investigators, limit the subject's ability to provide informed consent, or to comply with study procedures
• Pregnant, planning to become pregnant or lactating (digoxin and midazolam are Category C and D medications, respectively).

Sponsors & Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (3)

• Abou-Donia MB, El-Masry EM, Abdel-Rahman AA, McLendon RE, Schiffman SS. Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. J Toxicol Environ Health A. 2008;71(21):1415-29. doi: 10.1080/15287390802328630.

  PMID: 18800291 BACKGROUND

• Sylvetsky AC, Brown RJ, Blau JE, Walter M, Rother KI. Hormonal responses to non-nutritive sweeteners in water and diet soda. Nutr Metab (Lond). 2016 Oct 21;13:71. doi: 10.1186/s12986-016-0129-3. eCollection 2016.

  PMID: 27777606 BACKGROUND

• 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.

  PMID: 25231862 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Overweight

Interventions

trichlorosucrose

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Paule V Joseph, C.R.N.P.

  National Institute on Alcohol Abuse and Alcoholism (NIAAA)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paule V Joseph, C.R.N.P.

CONTACT

(301) 827-5234; paule.joseph@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2018
• First Posted: January 23, 2018
• Study Start: April 5, 2018
• Primary Completion (Estimated): December 26, 2027
• Study Completion (Estimated): December 26, 2027
• Last Updated: April 29, 2026

Record last verified: 2026-02-26

Locations

US (1)