Healthy VolunteersPhase 2NCT03407079
Effects of Sucralose on Drug Absorption and Metabolism (The SweetMeds Study)
A Phase 2 study testing Sucralose in people with Healthy Volunteers and Overweight, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers, Overweight
- What is being tested?
- Sucralose
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Apr 2018to 26 Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Show all 11Show fewer
- Able and willing to consume approximately 4 mg/kg sucralose daily or placebo in form of capsules for
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY8664111010, prpl@cc.nih.gov
About this study
Background:
Artificial sweeteners like sucralose are found in many foods and drinks. Sucralose might affect hormones and cause health changes.
Read more
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.
Read the detailed description
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
- glucose metabolism and incretin secretion
- lipid metabolism
- intestinal microflora
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:
- 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.
- Conditions
- Healthy Volunteers, Overweight
- Being tested
- Sucralose, Placebo
- Keywords
- Drug Metabolism, Artificial Sweetener, P-Glycoprotein, Cytochrome P450, Microbiome
- Medical subject headings
- Overweight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SucraloseOther
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.
PlaceboOther
Placebo capsules will be taken orally for 28 days
| Study group | Role | What they receive |
|---|---|---|
| Study Arm 1 | Experimental | Participants will receive sucralose capsules (approximately 4mg/kg/day) by mouth for 28 days. Receives: Other: Sucralose |
| Study Arm 2 | Placebo comparator | Participants will receive placebo capsules by mouth for 28 days. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 days
Secondary outcomes (1)
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
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2018
- Study start5 Apr 2018
- Primary completion26 Dec 2027 (estimated)
- Study completion26 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Paule V Joseph, C.R.N.P., Principal investigator, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03407079
- Sponsor's protocol ID
- 180047
- Other IDs
- 18-AA-0047
- Status last verified
- 26 Feb 2026
- First submitted
- 20 Jan 2018
- Last updated
- 5 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 18800291Sylvetsky 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.
PubMed 27777606Suez 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.
PubMed 25231862
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Sucralose on Drug Absorption and Metabolism (The SweetMeds Study)
- ClinicalTrials.gov ID
- NCT03407079
- Acronym / sponsor ID
- 180047
- Conditions
- Healthy Volunteers, Overweight
- Keywords
- Drug Metabolism, Artificial Sweetener, P-Glycoprotein, Cytochrome P450, Microbiome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)US National Institutes of Health
- Study start
- 5 Apr 2018 (actual)
- Primary completion
- 26 Dec 2027 (estimated)
- Study completion
- 26 Dec 2027 (estimated)
- First posted
- 23 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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
- glucose metabolism and incretin secretion
- lipid metabolism
- intestinal microflora
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:
- 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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study Arm 1 | Experimental | Other: SucraloseParticipants will receive sucralose capsules (approximately 4mg/kg/day) by mouth for 28 days. |
| Study Arm 2 | Placebo comparator | Other: PlaceboParticipants will receive placebo capsules by mouth for 28 days. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SucraloseSucralose 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. | Other | Study Arm 1 |
| PlaceboPlacebo capsules will be taken orally for 28 days | Other | Study Arm 2 |
Primary outcome
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
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.
1 secondary outcome
To investigate the effects of sucralose on glucose metabolism and incretin secretion, lipid metabolism, and intestinal microbiome
Time frame: 28 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Background: PubMed 18800291Abou-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.
- Background: PubMed 27777606Sylvetsky 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.
- Background: PubMed 25231862Suez 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Paule V Joseph, C.R.N.P. principal investigator
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sucralose in people with Healthy Volunteers and Overweight, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Paule V Joseph, C.R.N.P. ((301) 827-5234, paule.joseph@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03407079, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.