Intranasal Cocaine and Temperature Regulation During Exercise

Study Overview
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Brief Summary
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Assess the effects of intranasal cocaine on temperature regulation and whole-body sweat rate during exercise in warm environmental conditions.

Detailed Description
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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.

Official Title
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Intranasal Cocaine and Temperature Regulation During Exercise

Conditions
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Hyperthermia, Cocaine Use, Exercise

Intervention / Treatment
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* Drug: Cocaine
* Drug: Lidocaine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cocaine<br>Prior to entering the warm environmental conditions the participant will receive cocaine intranasally at a dose no higher than 3 mg per kilogram body mass. This dose will be given only once. | Drug: Cocaine<br>* Cocaine will be administered intranasally prior to entering the warm environmental conditions and performing 60 minutes of exercise.<br>|
| Placebo Comparator: Lidocaine<br>Prior to entering the warm environmental conditions the participant will receive lidocaine intranasally at a dose no higher than 3 mg per kilogram body mass. This dose will be given only once. | Drug: Lidocaine<br>* Lidocaine will be administered intranasally prior to entering the warm environmental conditions and performing 60 minutes of exercise.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in core body temperature | Core body temperature will be measured either from a temperature sensor pill or from a rectal thermometer | Within 30 minutes before exposure to warm environmental conditions, throughout 60 minutes of exercise, and during the 30 minute recovery period. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in skin temperature | Skin temperature will be measured from small temperature sensitive electrodes attached to the participant's skin | Within 30 minutes before exposure to warm environmental conditions, throughout 60 minutes of exercise, and during the 30 minute recovery period. | 
| Change in heart rate | Heart rate will be measured from ECG electrodes attached to the participant | Within 30 minutes before exposure to warm environmental conditions, throughout 60 minutes of exercise, and during the 30 minute recovery period. | 
| Change in whole body sweat rate | Whole body sweat rate will be measured by nude weight of the participant | Within 30 minutes before exposure to warm environmental conditions and immediately after the 30 minute recovery period. | 
| Change in blood pressure | Systolic and diastolic blood pressure will be measured from a cuff placed on the upper arm. | Within 30 minutes before exposure to warm environmental conditions, throughout 60 minutes of exercise, and during the 30 minute recovery period. | 
| Perceptual questionnaire on how hot one feels | Subjective assessment of how hot the subject feels. Title of Scale: Thermal Sensation Scale; Minimum value: 0 unbearably cold; Maximum value: 8: unbearably hot | These values will be obtained throughout the 60 minutes of exercise and during the 30 minute recovery period | 
| Perceptual questionnaire on how hard one feels they are exercising | Subjective assessment of how hard the subject feels they are exercising Title of scale: Rating of Perceived Exertion Borg Scale; Minimum value: 6 No exertion at all; Maximum value: 20 Maximum exertion | These values will be obtained throughout the 60 minutes of exercise and during the 30 minute recovery period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thermoregulation, sweating, skin blood flow