Investigating the Stability, Variability and Mechanism of Incorporation of Lipid Mediators Into Eccrine Sweat

Study Overview
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Brief Summary
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The purpose of this study is to see what the differences are in sweat (amount and small molecule content) collected from different sites of the body and by different methods of sweat stimulation. Additionally, the investigators want to know whether the amount and small molecule content of the sweat is the same in an individual over time, and the same across individuals at a given time. Finally, the investigators want to know how consumption of over-the-counter anti-inflammatory drugs such as ibuprofen will affect the inflammatory mediator content of sweat and how that compares to blood. This information will help to better understand the composition and behavior of sweat and assess its potential utility as a routine clinical tool in skin research.

Detailed Description
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Subjects will participate in 4 study day visits that will be scheduled about 1- week apart. During the first study visit, the investigators will compare sweat collected following pharmacological stimulation of sweating (using the drug pilocarpine) to sweat collected following physiological stimulation of sweating (using a stationary bicycle). During the second study visit, the investigators will collect sweat following stimulation of sweating by the drug pilocarpine from the inner part of the forearm (near the wrist) and also the upper surface of the thigh (near the knee). During the third study visit, the investigators will collect sweat following stimulation of sweating by the drug pilocarpine from the inner part of both forearms (near the wrist). During the fourth study visit, the investigators will collect a sweat sample following stimulation of sweating by the drug pilocarpine from the inner part of the forearm (near the wrist) and a blood sample (about one teaspoon) from the other arm. After blood and sweat collection, participants will consume 400 mg (two tablets) of ibuprofen. The investigators will then collect blood and sweat from 30 minutes, 2 hours and 4 hours after participants consume the ibuprofen.

Official Title
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Investigating the Stability, Variability and Mechanism of Incorporation of Lipid Mediators Into Eccrine Sweat

Conditions
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Stability & Variability of Lipid-derived Molecules in Sweat

Intervention / Treatment
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* Drug: Ibuprofen
* Other: Physiological induction of sweating
* Drug: Pilocarpine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 20-40 y Male Weight > 110 pounds Exclusion Criteria: Diagnosed active chronic diseases for which the individual is currently taking daily medication, including but not limited to: Diabetes mellitus Cardiovascular disease Cancer Gastrointestinal disorders Kidney disease Liver disease Bleeding disorders Asthma Autoimmune disorders Hypertension Osteoporosis Recent minor surgery (within 4 wk) or major surgery (within 16 wk) Recent antibiotic therapy (within 4 wk) Recent hospitalization (within 4 wk) Use of over-the-counter or prescription medications at the time of the study that directly affect endpoints of interest (e.g. hyperlipidemia, glycemic control, steroids, statins, anti-inflammatory agents, and weight loss aids) Adults who are not able to consent Under current medical supervision Ibuprofen intolerance or allergy Those with a bleeding disorder Current enrollee in a clinical research study. Individuals with blood clotting or platelet defect disorders Individuals with orthopedic limitations or cardiovascular risk that preclude participation in the physiological stimulation of sweat by light exercise portion of the study Individuals who are trained athletes or that regularly perform physical activity defined as vigorous by the Centers for Disease Control and Prevention

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single group<br>All subjects will participate in 4 study day visits in the same order. compare sweat collected following pharmacological stimulation of sweating (using the drug pilocarpine) to sweat collected following physiological induction of sweating (exercise using a stationary bicycle). compare sweat collected following stimulation of sweating by the drug pilocarpine from the inner part of the forearm (near the wrist) to upper surface of thigh (near the knee). collect sweat following stimulation of sweating by the drug pilocarpine from the inner part of both forearms (near the wrist). collect blood and sweat samples before and 30 minutes, 2 hours and 4 hours after consumption of 400 mg of ibuprofen. | Drug: Ibuprofen<br>* 400 mg ibuprofen given to inhibit cyclooxygenase metabolism<br>Other: Physiological induction of sweating<br>* 15 minutes exercise at 60-80% oxygen consumption to induce sweating<br>* Other names: Exercise;Drug: Pilocarpine<br>* Iontophoresis with a 1.5 milliampere (mA) current using a gel disc containing a 5% pilocarpine nitrate solution to induce sweating<br>* Other names: Pilogel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volar Forearm Sweat Lipid Mediator Concentrations Following Pilocarpine Stimulation | Approximately 150 lipid mediators will be measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Assayed lipid mediators include oxygenated lipids, endocannabinoids and endocannabinoid-like molecules, and sphingolipids. | measured at study visit 1, 2 and 3; detected lipid mediator concentrations for study visit 1 reported | 
| Volar Forearm Sweat Lipid Mediator Concentrations Following Exercise | Approximately 150 lipid mediators will be measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Assayed lipid mediators include oxygenated lipids, endocannabinoids and endocannabinoid-like molecules, and sphingolipids. | measured at study visit 1, detected lipid mediator concentrations reported | 
| Lower Back Sweat Lipid Mediator Concentrations Following Pilocarpine Stimulation | Approximately 150 lipid mediators will be measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Assayed lipid mediators include oxygenated lipids, endocannabinoids and endocannabinoid-like molecules, and sphingolipids. | measured at study visit 1, detected lipid mediator concentrations reported | 
| Anterior Distal Thigh Sweat Lipid Mediator Concentrations Following Pilocarpine Stimulation | Approximately 150 lipid mediators will be measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Assayed lipid mediators include oxygenated lipids, endocannabinoids and endocannabinoid-like molecules, and sphingolipids. | measured at study visit 2, detected lipid mediator concentrations reported | 
| Change in Plasma Lipid Mediator Concentrations Before and After Oral Ibuprofen Administration | Approximately 100 lipid mediators will be measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Assayed lipid mediators include oxygenated lipids, endocannabinoids, and endocannabinoid-like molecules. | measured at four timepoints at study visit 4, detected lipid mediator concentrations for first timepoint reported | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pilocarpine-stimulated Sweat Lipid Mediator Concentrations Before and After Oral Ibuprofen Administration | Approximately 100 lipid mediators will be measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Assayed lipid mediators include oxygenated lipids, endocannabinoids, and endocannabinoid-like molecules. | measured at four timepoints at study visit 4, detected lipid mediator concentrations for first timepoint reported | 
| Change in Plasma Ibuprofen Concentrations | Plasma concentration of ibuprofen prior to and 30 min, 2 hr and 4 hr after oral administration | measured at four timepoints at study visit 4 | 
| Change in Sweat Ibuprofen Concentrations | Sweat concentration of ibuprofen prior to and 30 min, 2 hr and 4 hr after oral administration | measured at four timepoints at study visit 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oxygenated lipids, metabolic profiling, sphingoid bases, ceramides, endocannabinoids, non-invasive sampling