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

• Sponsor: USDA, Western Human Nutrition Research Center (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT02935894
• Collaborator: University of California, Davis (Other)
• Enrollment: 14
• Location: 1
• Arm: 1
• Actual Duration (Months): 6.3
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Stability & Variability of Lipid-derived Molecules in Sweat	Drug: Ibuprofen; Other: Physiological induction of sweating; Drug: Pilocarpine	N/A

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Investigating the Stability, Variability and Mechanism of Incorporation of Lipid Mediators Into Eccrine Sweat
• Actual Study Start Date: Nov 28, 2016
• Actual Primary Completion Date: Jun 8, 2017
• Actual Study Completion Date: Jun 8, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Single group 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; 400 mg ibuprofen given to inhibit cyclooxygenase metabolism; Other: Physiological induction of sweating; 15 minutes exercise at 60-80% oxygen consumption to induce sweating; Other Names: Exercise ; Drug: Pilocarpine; Iontophoresis with a 1.5 milliampere (mA) current using a gel disc containing a 5% pilocarpine nitrate solution to induce sweating; Other Names: Pilogel

Outcome Measures

Primary Outcome Measures

1. Volar Forearm Sweat Lipid Mediator Concentrations Following Pilocarpine Stimulation [measured at study visit 1, 2 and 3; detected lipid mediator concentrations for study visit 1 reported]

   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.

2. Volar Forearm Sweat Lipid Mediator Concentrations Following Exercise [measured at study visit 1, detected lipid mediator concentrations reported]

   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.

3. Lower Back Sweat Lipid Mediator Concentrations Following Pilocarpine Stimulation [measured at study visit 1, detected lipid mediator concentrations reported]

   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.

4. Anterior Distal Thigh Sweat Lipid Mediator Concentrations Following Pilocarpine Stimulation [measured at study visit 2, detected lipid mediator concentrations reported]

   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.

5. Change in Plasma Lipid Mediator Concentrations Before and After Oral Ibuprofen Administration [measured at four timepoints at study visit 4, detected lipid mediator concentrations for first timepoint reported]

   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.

Secondary Outcome Measures

1. Change in Pilocarpine-stimulated Sweat Lipid Mediator Concentrations Before and After Oral Ibuprofen Administration [measured at four timepoints at study visit 4, detected lipid mediator concentrations for first timepoint reported]

   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.

2. Change in Plasma Ibuprofen Concentrations [measured at four timepoints at study visit 4]

   Plasma concentration of ibuprofen prior to and 30 min, 2 hr and 4 hr after oral administration

3. Change in Sweat Ibuprofen Concentrations [measured at four timepoints at study visit 4]

   Sweat concentration of ibuprofen prior to and 30 min, 2 hr and 4 hr after oral administration

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 40 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Western Human Nutrition Research Center	Davis	California	United States	95616

Sponsors and Collaborators

• USDA, Western Human Nutrition Research Center
• University of California, Davis

Investigators

• Principal Investigator: John W. Newman, Ph.D., USDA-ARS-Western Human Nutrition Research Center

Study Documents (Full-Text)

• Study Protocol - Feb 9, 2017
• Informed Consent Form - Feb 13, 2017
• Statistical Analysis Plan - Dec 5, 2017

More Information

Publications

None provided.

• Responsible Party: USDA, Western Human Nutrition Research Center
• ClinicalTrials.gov Identifier: NCT02935894
• Other Study ID Numbers: 929370
• First Posted: Oct 18, 2016
• Last Update Posted: Jun 1, 2018
• Last Verified: Apr 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by USDA, Western Human Nutrition Research Center: oxygenated lipids; metabolic profiling; sphingoid bases; ceramides; endocannabinoids; non-invasive sampling
• Additional relevant MeSH terms: Ibuprofen; Pilocarpine

Study Results

Participant Flow

Arm/Group Title	Single Group
Arm/Group Description	Subjects will participate in 4 study 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 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. Ibuprofen: 400 mg ibuprofen given to inhibit cyclooxygenase metabolism Physiological induction of sweating: 15 minutes exercise at 60-80% oxygen consumption to induce sweating Pilocarpine: Iontophoresis with a 1.5 milliampere (mA) current using a gel disc containing a 5% pilocarpine
Period Title: Overall Study
STARTED	14
COMPLETED	13
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Single Group
Arm/Group Description	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 on 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. Ibuprofen: 400 mg ibuprofen given to inhibit cyclooxygenase (COX) metabolism Physiological induction of sweating: 15 minutes exercise at 60-80% oxygen consumption to induce sweating Pilocarpine: Iontophoresis with a 1.5 milliampere (mA) current using a gel disc containing a
Overall Participants	14
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	14 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	14 100%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United States	14 100%
Height (centimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters]	179.2 (6.2)
Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	82.6 (15.9)
Body Mass Index (kilograms per square meter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms per square meter]	25.8 (5.0)
Perceived Exercise Intensity (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	1.6 (0.5)

Outcome Measures

1. Primary Outcome

Title	Volar Forearm Sweat Lipid Mediator Concentrations Following Pilocarpine Stimulation
Description	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.
Time Frame	measured at study visit 1, 2 and 3; detected lipid mediator concentrations for study visit 1 reported

Outcome Measure Data

Analysis Population Description

Of the 14 subjects recruited for this study, only 7 provided usable data for this primary outcome.

Arm/Group Title	Single Group
Arm/Group Description	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. Ibuprofen: 400 mg ibuprofen given to inhibit COX metabolism Physiological induction of sweating: 15 minutes exercise at 60-80% oxygen consumption to induce sweating Pilocarpine: Iontophoresis with a 1.5 milliampere (mA) current using a gel disc containing a 5% pilocarpine
Measure Participants	7
9-HODE	20 (9.8)
13-HODE	46 (28)
9-HOTrE	2.2 (1.2)
13-HOTrE	3.5 (1.8)
5-HETE	0.1 (0.07)
8-HETE	0.23 (0.062)
9-HETE	0.12 (0.062)
11-HETE	0.15 (0.055)
12-HETE	0.85 (0.94)
15-HETE	0.43 (0.25)
12-HEPE	0.086 (0.044)
9,10-e-DiHO	85 (37)
9,10-DiHOME	4.4 (3)
12,13-DiHOME	3.4 (2.3)
9,10-DiHODE	0.85 (1.1)
12,13-DiHODE	0.5 (0.31)
15,16-DiHODE	2.7 (3.9)
5,6-DiHETrE	5.3 (2.5)
8,9-DiHETrE	0.73 (0.43)
11,12-DiHETrE	0.51 (0.29)
14,15-DiHETrE	0.65 (0.4)
9,10-EpOME	1.7 (0.79)
12,13-EpOME	0.96 (0.29)
9,10-EpODE	0.55 (0.54)
12,13-EpODE	0.12 (0.066)
15,16-EpODE	3.5 (3.4)
9-KODE	14 (6.3)
13-KODE	7.2 (3.8)
12,13-Ep-9-KODE	3.7 (2.8)
5-KETE	0.025 (0.019)
LTB5	0.1 (0.094)
10-Nitrooleate	0.096 (0.054)
10-Nitrolinoleate	0.11 (0.069)
PGE1	0.24 (0.15)
PGE2	2.1 (1.8)
PGF2a	0.14 (0.14)
15-deoxy PGJ2	0.033 (0.012)
PGE3	0.13 (0.17)
Sum TriHOMEs	57 (56)
PEA	7.9 (6.8)
SEA	7.9 (6.7)
OEA	0.32 (0.38)
LEA	0.043 (0.035)
aLEA	0.0047 (0.0036)
Dihomo GLA EA	0.0022 (0.003)
AEA	0.019 (0.011)
DEA	0.17 (0.24)
1-OG	870 (1300)
2-OG	190 (270)
1-LG	300 (540)
2-LG	2.3 (1.1)
1-AG	14 (12)
2-AG	15 (30)
NO-Gly	0.48 (0.22)
NA-Gly	0.017 (0.02)
C14 Ceramide	1.4 (1.1)
C16 Ceramide	6.6 (4.7)
C18 Ceramide	1.2 (0.66)
C20 Ceramide	2 (1.4)
C24 Ceramide	5.7 (4.9)
18:1 Sphingosine	15 (8.9)

2. Primary Outcome

Title	Volar Forearm Sweat Lipid Mediator Concentrations Following Exercise
Description	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.
Time Frame	measured at study visit 1, detected lipid mediator concentrations reported

Outcome Measure Data

Analysis Population Description

Of the 14 subjects recruited for this study, only 7 provided usable data for this primary outcome.

Arm/Group Title	Single Group
Arm/Group Description	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. Ibuprofen: 400 mg ibuprofen given to inhibit COX metabolism Physiological induction of sweating: 15 minutes exercise at 60-80% oxygen consumption to induce sweating Pilocarpine: Iontophoresis with a 1.5 milliampere (mA) current using a gel disc containing a 5% pilocarpine
Measure Participants	7
9-HODE	2.4 (1.9)
13-HODE	5.2 (3.9)
9-HOTrE	0.6 (0.5)
13-HOTrE	1.5 (1.4)
5-HETE	0.023 (0.018)
8-HETE	0.14 (0.061)
9-HETE	0.029 (0.018)
11-HETE	0.012 (0.0061)
12-HETE	0.04 (0.031)
15-HETE	0.074 (0.054)
12-HEPE	0.029 (0.015)
9,10-e-DiHO	21 (12)
9,10-DiHOME	3.1 (1.8)
12,13-DiHOME	2.8 (1.6)
9,10-DiHODE	0.56 (0.68)
12,13-DiHODE	0.3 (0.12)
15,16-DiHODE	1.9 (2.3)
5,6-DiHETrE	0.026 (0.037)
8,9-DiHETrE	0.24 (0.25)
11,12-DiHETrE	0.022 (0.026)
14,15-DiHETrE	0.041 (0.018)
9,10-EpOME	0.46 (0.31)
12,13-EpOME	0.36 (0.22)
9,10-EpODE	0.19 (0.18)
12,13-EpODE	0.019 (0.014)
15,16-EpODE	0.82 (0.86)
9-KODE	1.5 (1.4)
13-KODE	0.89 (0.6)
12,13-Ep-9-KODE	3.4 (1.8)
5-KETE	0.02 (0.017)
LTB5	0.099 (0.082)
10-Nitrooleate	0.074 (0.043)
10-Nitrolinoleate	0.087 (0.078)
PGE1	0.85 (1)
PGE2	1.1 (1.3)
PGF2a	0.44 (0.74)
15-deoxy PGJ2	0.046 (0.036)
PGE3	0.18 (0.21)
Sum TriHOMEs	130 (130)
PEA	14 (25)
SEA	15 (25)
OEA	0.11 (0.093)
LEA	0.019 (0.01)
aLEA	0.0033 (0.0024)
Dihomo GLA EA	0.0023 (0.0036)
AEA	0.017 (0.025)
DEA	0.015 (0.013)
1-OG	11 (14)
2-OG	7 (7.3)
1-LG	2.1 (1.8)
2-LG	0.34 (0.36)
1-AG	1.8 (3.1)
2-AG	0.79 (1)
NO-Gly	0.15 (0.13)
NA-Gly	0.01 (0.012)
C14 Ceramide	0.23 (0.18)
C16 Ceramide	1 (1)
C18 Ceramide	0.29 (0.34)
C20 Ceramide	0.36 (0.34)
C24 Ceramide	0.88 (0.8)
18:1 Sphingosine	4.9 (4.6)

3. Primary Outcome

Title	Lower Back Sweat Lipid Mediator Concentrations Following Pilocarpine Stimulation
Description	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.
Time Frame	measured at study visit 1, detected lipid mediator concentrations reported

Outcome Measure Data

Analysis Population Description

Of the 14 subjects recruited for this study, only 4 provided usable data for this primary outcome.

Arm/Group Title	Single Group
Arm/Group Description	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. Ibuprofen: 400 mg ibuprofen given to inhibit COX metabolism Physiological induction of sweating: 15 minutes exercise at 60-80% oxygen consumption to induce sweating Pilocarpine: Iontophoresis with a 1.5 milliampere (mA) current using a gel disc containing a 5% pilocarpine
Measure Participants	4
9-HODE	17 (11)
13-HODE	81 (42)
9-HOTrE	1.8 (0.65)
13-HOTrE	2.6 (1.1)
5-HETE	0.15 (0.1)
8-HETE	0.23 (0.21)
9-HETE	0.12 (0.083)
11-HETE	0.2 (0.27)
12-HETE	0.3 (0.22)
15-HETE	0.32 (0.2)
12-HEPE	0.15 (0.11)
9,10-e-DiHO	36 (13)
9,10-DiHOME	2.6 (0.73)
12,13-DiHOME	2.2 (0.52)
9,10-DiHODE	0.38 (0.16)
12,13-DiHODE	0.34 (0.14)
15,16-DiHODE	0.55 (0.16)
5,6-DiHETrE	2.8 (1.8)
8,9-DiHETrE	0.1 (0.22)
11,12-DiHETrE	0.28 (0.039)
14,15-DiHETrE	0.34 (0.067)
9,10-EpOME	1.6 (1.1)
12,13-EpOME	1.6 (1.3)
9,10-EpODE	0.28 (0.15)
12,13-EpODE	0.2 (0.1)
15,16-EpODE	0.49 (0.34)
9-KODE	11 (9.2)
13-KODE	6 (2.9)
12,13-Ep-9-KODE	2.6 (0.94)
5-KETE	0.1 (0.12)
LTB5	0.13 (0.093)
10-Nitrooleate	0.75 (1.2)
10-Nitrolinoleate	0.26 (0.31)
PGE1	0.11 (0.046)
PGE2	0.62 (0.28)
PGF2a	0.27 (0.15)
PGE3	0.17 (0.13)
Sum TriHOMEs	12 (11)
PEA	47 (65)
SEA	53 (73)
OEA	0.55 (0.46)
LEA	0.14 (0.14)
aLEA	0.11 (0.14)
Dihomo GLA EA	0.05 (0.083)
AEA	0.14 (0.19)
DEA	0.028 (0.069)
1-OG	300 (210)
2-OG	46 (47)
1-LG	110 (82)
2-LG	2.6 (1.3)
1-AG	10 (12)
2-AG	2.6 (1.3)
NO-Gly	0.25 (0.26)
NA-Gly	0.027 (0.057)
C14 Ceramide	0.49 (0.28)
C16 Ceramide	1.7 (1.6)
C18 Ceramide	0.34 (0.32)
C20 Ceramide	0.33 (0.26)
C24 Ceramide	0.41 (0.28)
18:1 Sphingosine	8.1 (12)

4. Primary Outcome

Title	Anterior Distal Thigh Sweat Lipid Mediator Concentrations Following Pilocarpine Stimulation
Description	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.
Time Frame	measured at study visit 2, detected lipid mediator concentrations reported

Outcome Measure Data

Analysis Population Description

Of the 14 subjects recruited for this study, only 4 provided usable data for this primary outcome.

Arm/Group Title	Single Group
Arm/Group Description	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. Ibuprofen: 400 mg ibuprofen given to inhibit COX metabolism Physiological induction of sweating: 15 minutes exercise at 60-80% oxygen consumption to induce sweating Pilocarpine: Iontophoresis with a 1.5 milliampere (mA) current using a gel disc containing a 5% pilocarpine
Measure Participants	4
9-HODE	19 (9.9)
13-HODE	48 (24)
9-HOTrE	1.8 (0.54)
13-HOTrE	5.2 (1)
5-HETE	0.067 (0.059)
8-HETE	0.17 (0.066)
9-HETE	0.12 (0.043)
11-HETE	0.12 (0.075)
12-HETE	0.31 (0.14)
15-HETE	0.26 (0.28)
12-HEPE	0.13 (0.057)
9,10-e-DiHO	35 (5.5)
9,10-DiHOME	2.9 (0.89)
12,13-DiHOME	2.4 (0.69)
9,10-DiHODE	0.46 (0.095)
12,13-DiHODE	0.7 (0.13)
15,16-DiHODE	0.99 (0.31)
5,6-DiHETrE	2.7 (1.2)
8,9-DiHETrE	0.62 (0.45)
11,12-DiHETrE	0.19 (0.072)
14,15-DiHETrE	0.19 (0.087)
9,10-EpOME	1.7 (0.54)
12,13-EpOME	1.6 (0.47)
9,10-EpODE	0.8 (0.66)
12,13-EpODE	0.25 (0.14)
15,16-EpODE	0.95 (0.45)
9-KODE	21 (17)
13-KODE	9.3 (7.3)
12,13-Ep-9-KODE	3.3 (1.4)
5-KETE	0.04 (0.018)
LTB5	0.088 (0.068)
10-Nitrooleate	0.12 (0.14)
10-Nitrolinoleate	0.16 (0.019)
PGE1	0.18 (0.15)
PGE2	0.36 (0.38)
PGF2a	0.44 (0.45)
PGE3	0.15 (0.14)
Sum TriHOMEs	36 (14)
PEA	18 (6.4)
SEA	18 (5.8)
OEA	0.31 (0.24)
LEA	0.078 (0.039)
aLEA	0.022 (0.005)
Dihomo GLA EA	0.00037 (0.0058)
AEA	0.013 (0.005)
DEA	0.053 (0.061)
1-OG	200 (88)
2-OG	37 (16)
1-LG	81 (41)
2-LG	2.1 (0.6)
1-AG	13 (5.4)
2-AG	4.2 (0.72)
NO-Gly	0.23 (0.14)
NA-Gly	0.02 (0.013)
C14 Ceramide	0.24 (0.15)
C16 Ceramide	1.5 (1.2)
C18 Ceramide	0.31 (0.25)
C20 Ceramide	0.36 (0.32)
C24 Ceramide	1 (0.99)
18:1 Sphingosine	2.2 (4.5)

5. Primary Outcome

Title	Change in Plasma Lipid Mediator Concentrations Before and After Oral Ibuprofen Administration
Description	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.
Time Frame	measured at four timepoints at study visit 4, detected lipid mediator concentrations for first timepoint reported

Outcome Measure Data

Analysis Population Description

Of the 14 subjects recruited for this study, only 9 provided usable data for this primary outcome.

Arm/Group Title	Single Group
Arm/Group Description	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. Ibuprofen: 400 mg ibuprofen given to inhibit COX metabolism Physiological induction of sweating: 15 minutes exercise at 60-80% oxygen consumption to induce sweating Pilocarpine: Iontophoresis with a 1.5 milliampere (mA) current using a gel disc containing a 5% pilocarpine
Measure Participants	9
PGE1	0.126
PGE2	0.159
PGF2a	5.47
13-HODE	23
9-HODE	8.77
13-HOTE	1.56
9-HOTE	1.19
15-HETE	0.861
12-HETE	1.31
11-HETE	0.408
5-HETE	0.425
17-HDoHE	2.55
9,10-e-DiHO	10.4
12,13-DiHOME	4.13
9,10-DiHOME	4.44
15,16-DiHODE	15
12,13-DiHODE	1.77
9,10-DiHODE	0.458
14,15-DiHETrE	1.17
11,12-DiHETrE	1.11
5,6-DiHETrE	0.406
17,18-DiHETE	20.2
19,20-DiHDoPA	1.91
Sum TriHOMEs	7.88
9(10)-EpO	9.96
12(13)-EpOME	4.1
9(10)-EpOME	1.12
15(16)-EpODE	3.95
9(10)-EpODE	1.02
13-KODE	1.89
9-KODE	3.09
OEA	4.14
LEA	1.19
aLEA	0.0968
Dihomo GLA EA	0.168
AEA	0.627
DEA	0.298
DHEA	0.76
NO-Gly	3.5
NA-Gly	0.833
OG	393
LG	238
AG	20.7

6. Secondary Outcome

Title	Change in Pilocarpine-stimulated Sweat Lipid Mediator Concentrations Before and After Oral Ibuprofen Administration
Description	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.
Time Frame	measured at four timepoints at study visit 4, detected lipid mediator concentrations for first timepoint reported

Outcome Measure Data

Analysis Population Description

Of the 14 subjects recruited for this study, only 9 provided usable data for this primary outcome.

Arm/Group Title	Single Group
Arm/Group Description	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. Ibuprofen: 400 mg ibuprofen given to inhibit COX metabolism Physiological induction of sweating: 15 minutes exercise at 60-80% oxygen consumption to induce sweating Pilocarpine: Iontophoresis with a 1.5 milliampere (mA) current using a gel disc containing a 5% pilocarpine
Measure Participants	9
PGE1	0.453
PGE2	2.71
13-HODE	21.9
9-HODE	7.72
13-HOTE	1.08
9-HOTE	1.08
20-HETE	0.742
15-HETE	0.311
12-HETE	0.965
11-HETE	0.0882
8-HETE	0.0618
5-HETE	0.138
15-HEPE	0.0576
12-HEPE	0.0781
17-HDoHE	0.46
9,10-e-DiHO	58.4
12,13-DiHOME	1.89
9,10-DiHOME	3.61
15,16-DiHODE	1.49
12,13-DiHODE	0.332
9,10-DiHODE	0.35
14,15-DiHETrE	0.341
11,12-DiHETrE	0.231
5,6-DiHETrE	3.29
17,18-DiHETE	1.76
Sum TriHOMEs	31.7
9(10)-EpO	2.81
12(13)-EpOME	0.485
9(10)-EpOME	0.657
15(16)-EpODE	0.491
12(13)-EpODE	0.0703
9(10)-EpODE	0.194
13-KODE	2.17
9-KODE	5.35
12(13)-Ep-9-KODE	1.82
10-Nitrooleate	1.78
9-Nitrooleate	0.729
10-Nitrolinoleate	0.297
OEA	0.586
LEA	0.0447
NO-Gly	0.156
NA-Gly	0.0627
OG	61.5
LG	4.11
AG	4.2

7. Secondary Outcome

Title	Change in Plasma Ibuprofen Concentrations
Description	Plasma concentration of ibuprofen prior to and 30 min, 2 hr and 4 hr after oral administration
Time Frame	measured at four timepoints at study visit 4

Outcome Measure Data

Analysis Population Description

Of the 14 subjects recruited for this study, only 9 provided usable data for this primary outcome.

Arm/Group Title	Single Group
Arm/Group Description	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. Ibuprofen: 400 mg ibuprofen given to inhibit COX metabolism Physiological induction of sweating: 15 minutes exercise at 60-80% oxygen consumption to induce sweating Pilocarpine: Iontophoresis with a 1.5 milliampere (mA) current using a gel disc containing a 5% pilocarpine
Measure Participants	9
Prior to administration	0
30 min after administration	18.8
2 hr after administration	48.3
4 hr after administration	33.8

8. Secondary Outcome

Title	Change in Sweat Ibuprofen Concentrations
Description	Sweat concentration of ibuprofen prior to and 30 min, 2 hr and 4 hr after oral administration
Time Frame	measured at four timepoints at study visit 4

Outcome Measure Data

Analysis Population Description

Of the 14 subjects recruited for this study, only 9 provided usable data for this primary outcome.

Arm/Group Title	Single Group
Arm/Group Description	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. Ibuprofen: 400 mg ibuprofen given to inhibit COX metabolism Physiological induction of sweating: 15 minutes exercise at 60-80% oxygen consumption to induce sweating Pilocarpine: Iontophoresis with a 1.5 milliampere (mA) current using a gel disc containing a 5% pilocarpine
Measure Participants	9
Prior to administration	0
30 min after administration	0
2 hr after administration	0
4 hr after administration	0

Adverse Events

Time Frame	Adverse events collected from November 2016 to June 2017 (6 months)
Arm/Group Title	Single Group
Arm/Group Description	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. Ibuprofen: 400 mg ibuprofen given to inhibit COX metabolism Physiological induction of sweating: 15 minutes exercise at 60-80% oxygen consumption to induce sweating Pilocarpine: Iontophoresis with a 1.5 milliampere (mA) current using a gel disc containing a 5% pilocarpine
All Cause Mortality
	Single Group
	Affected / at Risk (%)	# Events
Total	0/14 (0%)
Serious Adverse Events
	Single Group
	Affected / at Risk (%)	# Events
Total	0/14 (0%)
Other (Not Including Serious) Adverse Events
	Single Group
	Affected / at Risk (%)	# Events
Total	0/14 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.