Obesity, Tuberculosis
Conditions
Keywords
Obesity, Pharmacokinetics, Pharmacodynamics, Dose individualization, Tuberculosis
Brief summary
This study is designed to measure drug concentrations in the blood of healthy volunteers administered a single dose of ethambutol. Our hypothesis is that volunteers with a body mass index (BMI) 25-40 kg/m2 will remove ethambutol more quickly from the blood than leaner volunteers, and those with a BMI \> 40 kg/m2 will have even greater clearance than those who are leaner.
Interventions
DRUGEthambutol
All volunteers in each category will receive a single dose of oral ethambutol based on American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of American (ATS/CDC/IDSA) TB treatment guidelines.1 We will not use any doses higher than the maximum dose recommended for daily administration by the current ATS/CDC/IDSA TB guidelines (which use ideal body weight for dosing): 40-55kg: 800 mg (two 400 mg tablets) 56-75kg: 1,200 mg (three 400 mg tablets) 76-90kg: 1,600 mg (four 400 mg tablets) \> 90 kg: No dosage recommendations so these volunteers will only receive 1,600 mg (four 400 mg tablets)
Sponsors
National Center for Research Resources (NCRR)
University of Texas Southwestern Medical Center
Texas Tech University Health Sciences Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male and female volunteers, age 18 years of age or older, of all racial and ethnic origins. English and/or Spanish speaking volunteers are eligible to participate. * We are recruiting 6 normal weight (BMI \<25 kg/m2), 6 obese (BMI 25-40 kg/m2), and 6 extremely obese (BMI \> 40 kg/m2) for this study. Half of each group will be male, the other half will be female.
Exclusion criteria
* Creatinine clearance \< 70 ml/min as estimated by the Cockcroft-Gault equation. * Pregnant or nursing or unwilling to use a reliable contraception method during the study period. The effects of ethambutol on pregnancy are unknown. In addition, the metabolic changes that accompany pregnancy may alter the concentration-time profile of ethambutol, so that the pregnancy and post-partum state would be a confounding variable. * Abnormal liver function tests: transaminases \>10 time the upper limit of normal, alkaline phosphatase \> 5 time the upper limit of normal, total bilirubin \>5 time the upper limit of normal. * History of allergy to ethambutol. * Ethambutol is contraindicated for any reason. * Suspected or documented mycobacterial infection. * History of gout.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Total Clearance of Ethambutol | Blood samples will be collected over a 24 hour period (0, 2, 6, 11, 18, and 24 hours) |
Countries
United States
Participant flow
Recruitment details
Recruitment of volunteers by fliers.
Participants by arm
| Arm | Count |
|---|---|
| Ethambutol All volunteers received a single dose of oral ethambutol based on American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of American (ATS/CDC/IDSA) TB treatment guidelines. No doses were higher than the maximum dose recommended for daily administration by the current ATS/CDC/IDSA TB guidelines (which use ideal body weight for dosing):
40-55kg: 800 mg (two 400 mg tablets) 56-75kg: 1,200 mg (three 400 mg tablets) 76-90kg: 1,600 mg (four 400 mg tablets) \> 90 kg: No dosage recommendations so these volunteers will only receive 1,600 mg (four 400 mg tablets) | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | Ethambutol |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Age Continuous | 36.6 years STANDARD_DEVIATION 11.3 |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 18 |
| serious Total, serious adverse events | 0 / 18 |
Outcome results
Primary
Total Clearance of Ethambutol
Time frame: Blood samples will be collected over a 24 hour period (0, 2, 6, 11, 18, and 24 hours)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ethambutol | Total Clearance of Ethambutol | 80.8 L/h | Standard Deviation 18.6 |