Healthy
Conditions
Keywords
Dichloroacetate, Chloral Hydrate, Metabolism
Brief summary
This is a research study to look at how Dichloroacetate (DCA), and investigational drug and chloral hydrate are broken down in the body. The purpose of the study is to better understand how humans metabolize these two common chemicals that are widely present in the environment. The study focuses on how the drug chloral hydrate is broken down and how it effects DCA
Detailed description
The subject's general health is assessed by a history and physical exam and routine blood work. I normal the individual undergoes five nights of receiving 1.5ug/kg of chloral hydrate. On day 6 the individual receives 2.5 micrograms/kg of Dichloroacetate (DCA) and kinetics are drawn. After 30 days the subject comes back and receives 1.5ug/kg of chloral hydrate for five nights and has kinetics drawn on night one and five. On days 6-9 the subject returns for a blood draw. After 30 days the same process as above is done except the subject receives 1gram of chloral hydrate for five nights and 25mg/kg of Dichloroacetate one day then 30 days later the subject receives 1gram of chloral hydrate for five nights and has kinetics done on night one and five and blood samples drawn on days 6-9
Interventions
DRUGDichloroacetate environmental dose
On day 6 they receive Dichloroacetate 2.5 ug/kg orally times 1 and have pharmacokinetics.
DRUGChloral Hydrate environmental dose
Study subjects are given 1.5 ug/kg of Chloral Hydrate for 5 nights and pharmacokinetics are done on night 1 and 5.
DRUGDichloroacetate therapeutic dose
Subjects receive 25 mg/kg DCA on Day 6. Pharmacokinetics are done on nights 1 and nights 5.
DRUGChloral Hydrate therapeutic dose
Subject is given 25 mg/kg of Chloral Hydrate for five nights.
Sponsors
National Institutes of Health (NIH)
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* healthy * normal screening labs
Exclusion criteria
* no gastrointestinal surgery * no smoking * no medication * not pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma DCA (Microgram/ml) After 5 Days of Therapeutic Level Chloral Hydrate on Arm 2A. | 6 Days | After 5 days of of therapeutic level Chloral Hydrate, the levels of Dichloroacetate in the plasma were measured. |
| Difference in Half Lives 5 Day Less One Day Exposure in Trichloroacetate | 5 days | Elimination Half-life Difference on Arm 2B for 13C-Labeled trichloroacetate between day 5 (prolonged exposure) and day 1 (de novo exposure) after therapeutic level exposure to Chloral Hydrate. This outcome only applies to Period 4. Trichloroacetate is a marker, not an intervention. |
| Urinary Maleylacetone Levels After 5 Day Exposure to Therapeutic Chloral Hydrate (Arm 2B) | 5 days | The levels were clinically indetectable at baseline and the question was whether or not substantive levels would be noted at after 5 days exposure to Chloral Hydrate. Detectable, but low levels were detected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Detectable DCA After Day 1 in Serum (0=No 1=Yes) | 1 day | All four arms receive Chloral Hydrate on Day 1 (arms 1A and 1B environmental levels) and (arms 2A and 2B therapeutic levels). The question is could Dichloroacetate be detected in serum at the end of day 1. This analysis is purely descriptive, and no comparisons were planned. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited using an ad approved by the Institutional Review Board (IRB) and by undergoing a screening exam to determine eligibility.
Pre-assignment details
There were 27 total participants, with 4 eligible sessions (periods) for each, with the order to be randomized. As per CT.Gov instructions, the periods are identified by treatment rather than order.There were no planned comparisons between the arms of this pharmacological study. Withdrawals entered but did not reach baseline.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects Intent was to have all subjects participate in all sessions (periods) | 27 |
| Total | 27 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants |
| Age, Continuous | 28.0 years STANDARD_DEVIATION 7.9 |
| Region of Enrollment United States | 27 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 7 | 3 / 8 | 2 / 8 | 2 / 8 |
| serious Total, serious adverse events | 0 / 7 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Difference in Half Lives 5 Day Less One Day Exposure in Trichloroacetate
Elimination Half-life Difference on Arm 2B for 13C-Labeled trichloroacetate between day 5 (prolonged exposure) and day 1 (de novo exposure) after therapeutic level exposure to Chloral Hydrate. This outcome only applies to Period 4. Trichloroacetate is a marker, not an intervention.
Time frame: 5 days
Population: This applies only to Arm 2B (Therapeutic Chloral Hydrate without DCA.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Therapeutic Chloral Hydrate and DCA (2A) | Difference in Half Lives 5 Day Less One Day Exposure in Trichloroacetate | 2432 minutes | Standard Deviation 1403 |
Comparison: Only relevant to Arm 2B.p-value: 0.001795% CI: [1260, 3606]t-test, 2 sided
Primary
Plasma DCA (Microgram/ml) After 5 Days of Therapeutic Level Chloral Hydrate on Arm 2A.
After 5 days of of therapeutic level Chloral Hydrate, the levels of Dichloroacetate in the plasma were measured.
Time frame: 6 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Therapeutic Chloral Hydrate and DCA (2A) | Plasma DCA (Microgram/ml) After 5 Days of Therapeutic Level Chloral Hydrate on Arm 2A. | 1.64 micrograms/ml | Standard Deviation 0.4 |
Comparison: No comparison is relevant. The statistical method is how we obtained the point estimate and confidence interval. No test was intended.95% CI: [1.31, 1.97]
Primary
Urinary Maleylacetone Levels After 5 Day Exposure to Therapeutic Chloral Hydrate (Arm 2B)
The levels were clinically indetectable at baseline and the question was whether or not substantive levels would be noted at after 5 days exposure to Chloral Hydrate. Detectable, but low levels were detected.
Time frame: 5 days
Population: all eligible participants to arm 2B (Period 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Therapeutic Chloral Hydrate and DCA (2A) | Urinary Maleylacetone Levels After 5 Day Exposure to Therapeutic Chloral Hydrate (Arm 2B) | 0.38 micrograms per ml clorohydrate | Standard Deviation 0.17 |
Comparison: Only relevant for arm 2B95% CI: [0.24, 0.51]
Secondary
Detectable DCA After Day 1 in Serum (0=No 1=Yes)
All four arms receive Chloral Hydrate on Day 1 (arms 1A and 1B environmental levels) and (arms 2A and 2B therapeutic levels). The question is could Dichloroacetate be detected in serum at the end of day 1. This analysis is purely descriptive, and no comparisons were planned.
Time frame: 1 day
Population: All eligible session completers
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Therapeutic Chloral Hydrate and DCA (2A) | Detectable DCA After Day 1 in Serum (0=No 1=Yes) | 0 participants |
| Environmental Chloral Hydrate (1B) | Detectable DCA After Day 1 in Serum (0=No 1=Yes) | 0 participants |
| Therapeutic Chloral Hydrate and DCA (2A) | Detectable DCA After Day 1 in Serum (0=No 1=Yes) | 0 participants |
| Therapeutic Chloral Hydrate (2B) | Detectable DCA After Day 1 in Serum (0=No 1=Yes) | 0 participants |