Effects of Sucralose on Drug Absorption and Metabolism (The SweetMeds Study)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
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....
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •INCLUSION CRITERIA:
- •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
- •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
排除标准
- •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).
研究组 & 干预措施
Study Arm 2
Participants will receive placebo capsules by mouth for 28 days.
干预措施: Placebo (Other)
Study Arm 1
Participants will receive sucralose capsules (approximately 4mg/kg/day) by mouth for 28 days.
干预措施: Sucralose (Other)
结局指标
主要结局
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.
时间窗: 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.
次要结局
- To investigate the effects of sucralose on glucose metabolism and incretin secretion, lipid metabolism, and intestinal microbiome(28 days)