Cocaine Use, Exercise, Hyperthermia
Conditions
Keywords
thermoregulation, sweating, skin blood flow
Brief summary
Assess the effects of intranasal cocaine on temperature regulation and whole-body sweat rate during exercise in warm environmental conditions.
Detailed description
Previously it was shown that intranasal cocaine attenuates skin blood flow and sweating responses during passive heat stress, when compared to placebo. However, nothing is known about the effects of cocaine on whole-body temperature regulation during mild to moderate exercise in warm environmental condition. This project will test the hypothesis that intranasal cocaine attenuates whole-body sweat rate, resulting in greater elevations in core temperature during mild to moderate exercise in warm environmental conditions. Primary data include core temperature, skin temperatures, and whole body sweat rate. Secondary variables include cardiovascular responses, perceptions of exercise exertion and thermal comfort, and metabolic heat production. Intranasal lidocaine will be used as the placebo for cocaine. The selection of the drug administered during the first experimental trial will be randomized, with the other drug administered during the second experimental trial.
Interventions
DRUGCocaine
Cocaine (cocaine hydrochloride 4% nasal solution) will be administered (3 mg/kg) intranasally prior to entering the warm environmental conditions and performing 60 minutes of exercise.
DRUGLidocaine
Lidocaine (lidocaine hydrochloride 4% nasal solution) will be administered (3 mg/kg) intranasally prior to entering the warm environmental conditions and performing 60 minutes of exercise.
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Investigator)
Masking description
Our research nurse will know whether the participant will receive cocaine or lidocaine. All others involved in the protocol, including the participant, will not know which agent they received for which trial.
Intervention model description
We will conduct a double-blind, placebo-controlled, crossover study. Following informed consent and screening, eligible participants will be randomized to complete the cocaine or the lidocaine (placebo) trial first, with the other agent administered during the subsequent visit. During these experimental visits, we will first obtain pre-drug temperature and cardiovascular data, which will be followed by administer of cocaine or lidocaine intranasally. Participants will then enter the chamber set to warm environmental conditions. After further instrumentation in the warm environment, participants will perform mild to moderate intensity physical activity for 60 minutes. Throughout the 60 minutes of physical activity we will record body temperature and cardiovascular responses. Upon concluding the physical activity, subjects will rest while body temperature and cardiovascular responses are obtained post-physical activity.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* 18 to 50 years of age * Healthy * Body mass index less than 31 kg/m\^2 * Speak English * Systolic blood pressure \<140 mmHg * Diastolic blood pressure \<90 mmHg
Exclusion criteria
* Subjects not in the defined age range * Participants who have cardiac, respiratory, neurological, and/or metabolic illnesses * Any known history of renal or hepatic insufficiency/disease * Pregnancy or breast feeding * Body mass less than 60 kilograms * Current smokers, as well as individuals who regularly smoked within the past 3 years * Individuals with a history of drug abuse within the past 5 years * Individuals who have an unexplained positive urine drug screen (e.g., some agents cause false-positive results and when agent abstained the drug screen is negative, one example could be an over the counter supplement) * Currently taking pain modifying medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Core Temperature | Core temperature is measured at baseline and at 60 minutes of heat exposure. | Core temperature will be measured either from a temperature sensor pill or from a rectal temperature probe. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| End Skin Temperature | Measured at the end of heat exposure, 90 minutes from cocaine/lidocaine administration | Skin temperature will be measured from small temperature sensitive electrodes attached to the participant's skin |
| End Heart Rate | Measured at the end of heat exposure, 90 minutes from Cocaine/ lidocaine administration | Heart rate will be measured from ECG electrodes attached to the participant |
| Whole Body Sweat Rate | Within 30 minutes before exposure to warm environmental conditions (before cocaine/ lidocaine administration) and immediately after the heat exposure (90 minutes post cocaine/ lidocaine administration) | Whole body sweat rate is calculated by subtracting the participants post-heat exposure nude body weight from their pre-heat exposure nude body weight |
| End Mean Arterial Pressure | Measured at the end of heat exposure, 90 minutes from cocaine/ lidocaine administration | Systolic and diastolic blood pressure will be measured from a cuff placed on the upper arm. |
| End Thermal Sensation | These values will be obtained at end of the 60 minute heat exposure (90 minutes post cocaine/ lidocaine administration) | Subjective assessment of how hot the subject feels. Title of Scale: Thermal Sensation Scale; Minimum value: -50 unbearably cold; Maximum value: 50: unbearably hot Scale presents numbers in increments of 5 |
Countries
United States
Participant flow
Recruitment details
3 participants who signed the consent were withdrawn from the study prior to visit 1 due to either elevated bp at screening visit or they started a new medication that disqualified them from participating in this study.
Participants by arm
| Arm | Count |
|---|---|
| Hot-Humid: Cocaine First Then Lidocaine Participants will complete two trials in environmental conditions 38 degrees Celsius with 40% humidity.
Cocaine will be administered intranasally prior to entering the warm environmental conditions and performing 60 minutes of exercise on visit 1. Lidocaine will be administered intranasally prior to entering the warm environmental conditions and performing 60 minutes of exercise on visit 2. | 6 |
| Hot-Humid: Lidocaine First Then Cocaine Participants will complete two trials in environmental conditions 38 degrees Celsius with 40% humidity.
Lidocaine will be administered intranasally prior to entering the warm environmental conditions and performing 60 minutes of exercise on visit 1. Cocaine will be administered intranasally prior to entering the warm environmental conditions and performing 60 minutes of exercise on visit 2. | 7 |
| Hot-Dry: Cocaine First Then Lidocaine Participants will complete 2 trials in environmental conditions 41 degrees Celsius with 15% humidity.
Cocaine will be administered intranasally prior to entering the warm environmental conditions and performing 60 minutes of exercise on visit 1. Lidocaine will be administered intranasally prior to entering the warm environmental conditions and performing 60 minutes of exercise on visit 2. | 6 |
| Hot-Dry: Lidocaine First Then Cocaine Participants will complete 2 trials in environmental conditions 41 degrees Celsius with 15% humidity.
Lidocaine will be administered intranasally prior to entering the warm environmental conditions and performing 60 minutes of exercise on visit 1. Cocaine will be administered intranasally prior to entering the warm environmental conditions and performing 60 minutes of exercise on visit 2. | 4 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Hot-Humid: Cocaine First Then Lidocaine | Hot-Humid: Lidocaine First Then Cocaine | Hot-Dry: Cocaine First Then Lidocaine | Hot-Dry: Lidocaine First Then Cocaine | Total |
|---|---|---|---|---|---|
| Age, Continuous | 30 years STANDARD_DEVIATION 5 | 32 years STANDARD_DEVIATION 3 | 28 years STANDARD_DEVIATION 7 | 28 years STANDARD_DEVIATION 4 | 30 years STANDARD_DEVIATION 5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 6 Participants | 5 Participants | 4 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 6 Participants | 3 Participants | 3 Participants | 17 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 4 Participants | 1 Participants | 11 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 2 Participants | 3 Participants | 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 | 0 / 13 | 0 / 13 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 13 | 0 / 13 | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Change in Core Temperature
Core temperature will be measured either from a temperature sensor pill or from a rectal temperature probe.
Time frame: Core temperature is measured at baseline and at 60 minutes of heat exposure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hot-Humid: Cocaine | Change in Core Temperature | 1.19 Celsius | Standard Deviation 0.32 |
| Hot-Humid: Lidocaine | Change in Core Temperature | 1.09 Celsius | Standard Deviation 0.33 |
| Hot-Dry: Cocaine | Change in Core Temperature | 1.20 Celsius | Standard Deviation 0.27 |
| Hot-Dry: Lidocaine | Change in Core Temperature | 0.89 Celsius | Standard Deviation 0.23 |
Secondary
End Heart Rate
Heart rate will be measured from ECG electrodes attached to the participant
Time frame: Measured at the end of heat exposure, 90 minutes from Cocaine/ lidocaine administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hot-Humid: Cocaine | End Heart Rate | 151 BPM | Standard Deviation 21 |
| Hot-Humid: Lidocaine | End Heart Rate | 147 BPM | Standard Deviation 18 |
| Hot-Dry: Cocaine | End Heart Rate | 147 BPM | Standard Deviation 20 |
| Hot-Dry: Lidocaine | End Heart Rate | 134 BPM | Standard Deviation 18 |
Secondary
End Mean Arterial Pressure
Systolic and diastolic blood pressure will be measured from a cuff placed on the upper arm.
Time frame: Measured at the end of heat exposure, 90 minutes from cocaine/ lidocaine administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hot-Humid: Cocaine | End Mean Arterial Pressure | 85 mmHg | Standard Deviation 7 |
| Hot-Humid: Lidocaine | End Mean Arterial Pressure | 89 mmHg | Standard Deviation 8 |
| Hot-Dry: Cocaine | End Mean Arterial Pressure | 86 mmHg | Standard Deviation 10 |
| Hot-Dry: Lidocaine | End Mean Arterial Pressure | 87 mmHg | Standard Deviation 9 |
Secondary
End Skin Temperature
Skin temperature will be measured from small temperature sensitive electrodes attached to the participant's skin
Time frame: Measured at the end of heat exposure, 90 minutes from cocaine/lidocaine administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hot-Humid: Cocaine | End Skin Temperature | 35.83 Celsius | Standard Deviation 0.44 |
| Hot-Humid: Lidocaine | End Skin Temperature | 35.57 Celsius | Standard Deviation 0.59 |
| Hot-Dry: Cocaine | End Skin Temperature | 35.80 Celsius | Standard Deviation 0.81 |
| Hot-Dry: Lidocaine | End Skin Temperature | 35.39 Celsius | Standard Deviation 0.99 |
Secondary
End Thermal Sensation
Subjective assessment of how hot the subject feels. Title of Scale: Thermal Sensation Scale; Minimum value: -50 unbearably cold; Maximum value: 50: unbearably hot Scale presents numbers in increments of 5
Time frame: These values will be obtained at end of the 60 minute heat exposure (90 minutes post cocaine/ lidocaine administration)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hot-Humid: Cocaine | End Thermal Sensation | 31 units on a scale | Standard Deviation 14 |
| Hot-Humid: Lidocaine | End Thermal Sensation | 37 units on a scale | Standard Deviation 9 |
| Hot-Dry: Cocaine | End Thermal Sensation | 26 units on a scale | Standard Deviation 12 |
| Hot-Dry: Lidocaine | End Thermal Sensation | 27 units on a scale | Standard Deviation 15 |
Secondary
Whole Body Sweat Rate
Whole body sweat rate is calculated by subtracting the participants post-heat exposure nude body weight from their pre-heat exposure nude body weight
Time frame: Within 30 minutes before exposure to warm environmental conditions (before cocaine/ lidocaine administration) and immediately after the heat exposure (90 minutes post cocaine/ lidocaine administration)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hot-Humid: Cocaine | Whole Body Sweat Rate | 0.83 L/hour | Standard Deviation 0.25 |
| Hot-Humid: Lidocaine | Whole Body Sweat Rate | 0.79 L/hour | Standard Deviation 0.27 |
| Hot-Dry: Cocaine | Whole Body Sweat Rate | 0.79 L/hour | Standard Deviation 0.15 |
| Hot-Dry: Lidocaine | Whole Body Sweat Rate | 0.84 L/hour | Standard Deviation 0.15 |