Status and phase
Conditions
Treatments
About
More than 250 million courses of antibiotics are prescribed annually in the ambulatory care setting in the United States alone, including more than 40 million in children under 18 years of age. The perception that antibiotic use has minimal attendant adverse side effects contributes to the over-utilization of antibiotics in clinical circumstances when they are not strictly indicated. We have learned much about the human microbiome. The emerging view is of profound life-long bi-directional interactions between our microbiota and our cells. Perturbations in the microbiota affect metabolic, immune, and cognitive physiology in experimental animal models. When a person takes an antibiotic, the antibiotic diffuses via the blood into all body compartments, selecting for resistance. We propose to examine the effects of two commonly used antibiotics (the beta-lactam, amoxicillin and the macrolide azithromycin) on human microbial populations and on metabolic and immune physiology, studying healthy human volunteers in a randomized controlled clinical trial at the NIH Clinical Center. Our hypothesis is that in addition to acutely perturbing the human microbiome, these agents will have measurable metabolic and immunologic effects, with residual effects in the weeks that follow. To test this hypothesis, we will assess the effects of a brief therapeutic course of antibiotics on microbiome and metagenome composition. After an initial evaluation period, antibiotics will be given for 7 days or 5 days (depending on the antibiotic), and there will be a post-treatment evaluation. A control group will receive no drug intervention. Specimens will be obtained from multiple sites at each of 10 time points occurring before, during, and after antibiotic administration, and used for estimating bacterial and fungal composition and gene content. We will also assess the effects of the antibiotic course on markers of innate and adaptive immunity as well as markers of metabolic and hormonal physiology. A subgroup of subjects will be studied in the clinical center metabolic chamber to assess 24-hour energy expenditure and its components (sleeping, diet-induced, and activity energy expenditure), as well as macronutrient oxidation rates (carbohydrate, fat, and protein), during 3 of the 10 study visits. In addition to the primary data analyses, we will build a model that integrates the temporal data to begin to understand the complex intertwined physiology between microbiome and host.
Full description
More than 250 million courses of antibiotics are prescribed annually in the ambulatory care setting in the United States alone, including more than 40 million in children under 18 years of age. The perception that antibiotic use has minimal attendant adverse side effects contributes to the over-utilization of antibiotics in clinical circumstances when they are not strictly indicated. We have learned much about the human microbiome. The emerging view is of profound life-long bi-directional interactions between our microbiota and our cells. Perturbations in the microbiota affect metabolic, immune, and cognitive physiology in experimental animal models. When a person takes an antibiotic, the antibiotic diffuses via the blood into all body compartments, selecting for resistance. We propose to examine the effects of two commonly used antibiotics (the beta-lactam, amoxicillin and the macrolide azithromycin) on human microbial populations and on metabolic and immune physiology, studying healthy human volunteers in a randomized controlled clinical trial at the NIH Clinical Center. Our hypothesis is that in addition to acutely perturbing the human microbiome, these agents will have measurable metabolic and immunologic effects, with residual effects in the weeks that follow. To test this hypothesis, we will assess the effects of a brief therapeutic course of antibiotics on microbiome and metagenome composition. After an initial evaluation period, antibiotics will be given for 7 days or 5 days (depending on the antibiotic), and there will be a post-treatment evaluation. A control group will receive no drug intervention. Specimens will be obtained from multiple sites at each of 10 time points occurring before, during, and after antibiotic administration, and used for estimating bacterial and fungal composition and gene content. We will also assess the effects of the antibiotic course on markers of innate and adaptive immunity as well as markers of metabolic and hormonal physiology. A subgroup of subjects will be studied in the Clinical Center metabolic chamber to assess 24-hour energy expenditure and its components (sleeping, diet-induced, and activity energy expenditure), as well as macronutrient oxidation rates (carbohydrate, fat, and protein), during 3 of the 10 study visits. In addition to the primary data analyses, we will build a model that integrates the temporal data to begin to understand the complex intertwined physiology between microbiome and host.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Healthy women and men will be eligible for study participation if they meet the following criteria:
SUBJECT EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from study participation:
Body Mass Index (BMI) greater than or equal to 35 or less than or equal to 18 kg/M(2).
Vital signs outside of acceptable range at Screening Visit, i.e., blood pressure >160/100, oral temperature >100 degrees F, pulse >100.
Use of any of the following drugs or devices within the last 6 months:
Illicit drug use, including amphetamines, cocaine, or heroin, within the last 6 months. Marijuana use is not exclusionary.
Chronic smokers and subjects who use smokeless tobacco products (due to known effects of tobacco on the oral microbiome).
Claustrophobia.
Use of antacids (proton pump inhibitors, sucralfate, H1 and H2 antagonists, and those containing aluminum magnesium) within the last 3 months.
Use of laxatives or enemas within the last 3 months.
Diagnostic colonoscopy within the last 6 months.
Use of topical antibiotics or topical steroids on the face, scalp, or neck, or on arms, forearms, or hands within the previous 30 days.
Use of vaginal/vulvar medications, including antifungals, within the previous 30 days. Subjects may continue to use permitted vaginal contraceptives (spermicides and female condoms) until 24 hours prior to sampling
Use of isotretinoin within the past 5 years.
Intranasal influenza vaccination within the last 6 months due to effects on mucosal immunity.
Acute disease at the time of enrollment (defer enrollment until subject recovers). Acute disease is defined as the presence of a moderate or severe illness with or without fever.
Chronic, clinically significant (unresolved, requiring ongoing medical management or medication) pulmonary, cardiovascular, dermatologic, endocrine, GI, hepatic, or renal functional abnormality, as determined by medical history, physical examination, and/or laboratory testing. Includes, but not limited to:
Genitourinary/Gynecologic conditions, including:
History of cancer except for squamous or basal cell carcinomas of the skin that have been medically managed by local excision.
Unstable dietary history as defined by major changes in diet during the previous month, where the subject has eliminated or significantly increased a major food group in the diet.
Recent history of excessive alcohol consumption defined as more than five 1.5-ounce servings of 80-proof distilled spirits, five 12-ounce servings of beer, or five 5-ounce servings of wine at one sitting over the last 30 days.
Positive test for HIV, hepatitis B virus, or hepatitis C virus indicating infection (hepatitis B seropositivity conferred by vaccination is not exclusionary).
Any confirmed or suspected condition/state of immunosuppression or immunodeficiency (primary or acquired).
Major surgery of the GI tract, including cholecystectomy or appendectomy, in the past 5 years. Any major bowel resection at any time.
History of gastric stapling, lap band, or surgical procedure for treatment of obesity.
History of GI disorders or diseases including:
Active behavioral or psychiatric conditions that would be incompatible with a safe and successful participation in the study, including major depression, anxiety disorder, schizophrenia, and presence of psychotic symptoms.
Active eating disorders, including anorexia nervosa, bulimia, or binge eating syndrome.
Use of weight-loss drugs within the past 5 years.
Weight change (intended or unintended; loss or gain) of more than 10% of total body weight in the 3 months before admission.
Regular urinary incontinence necessitating use of incontinence protection garments.
Female who is pregnant, intending to become pregnant, or lactating.
History of recurrent rashes within the past 6 months.
At the time of the screening visit:
Subjects who are unable to complete required study visits per allotted visit windows.
Any condition that, in the opinion of the investigator, contraindicates participation in this study.
Primary purpose
Allocation
Interventional model
Masking
210 participants in 3 patient groups
Loading...
Central trial contact
Lurline Wu, C.R.N.P.; Christa S Zerbe, M.D.
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal