Clinical trial NCT01168739: Effect of Combined Exercise, Heat, and Quercetin Supplementation on Whole Body Stress Response
Official title: Effect of Combined Exercise, Heat, and Quercetin Supplementation on Whole Body Stress Response
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heat Acclimation and Thermotolerance
Keywords: thermotolerance
heat acclimation
quercetin
exertional heat illness
gastrointestinal barrier permeability
Lead sponsor: University of New Mexico
Sponsor class: OTHER
Collaborators: name: Gatorade Sports and Science Institute
name: Quercegen Pharmaceuticals
First posted: 2010-07-23
Enrollment: 9
Sex: MALE
Minimum age (years): 18
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to determine whether dietary quercetin supplementation effects thermotolerance and heat acclimation in human subjects exposed to exercise/heat stress.

Specific Aim I. To determine if quercetin in combination with repeated bouts of thermally stressful exercise will impact intestinal barrier function. The investigators will examine urinary lactulose excretion, plasma endotoxin,plasma quercetin, inflammatory cytokines (TNF-a \& Il-6), anti-inflammatory cytokines (Il-10), and HSP70 and HSF-1 content of peripheral blood mononuclear cells.

Specific Aim II. To determine whether quercetin's suppresses the ability of human subjects to acclimate to exercise/heat stress. The investigators will examine body temperatures, heart rates, physiological strain, sweat and plasma volume responses to standardized heat tolerance tests.

Detailed description: Overall Protocol:

This study will involve a repeated-measures design (2 conditions) in which subjects will perform exercise in the heat. Each condition will begin with an Intestinal Permeability Measurement (IP1), where subjects will be admitted to the General Clinical Research Center (GCRC), drinking a test solution and collecting their urine for 8 hours to measure intestinal integrity prior to heat stress. This will be followed by a Heat Tolerance Trial (HT1: 50min exercise at 50% VO2max in environmental chamber controlled at 56oC, 20%RF), used as a baseline measurement of subject's capacity to work in the heat. Following HT1 each subject will perform 7 Days of Heat Acclimation (HA)exercise (controlled hyperthermia design, each subject will elevate core temperature \>39oC in 50min during 50 minutes of exercise in environmental chamber controlled at 56oC, 20%RF; rest 10 min in environmental chamber; then perform another 50min of exercise at this elevated core temperature). On days 1 and 7 of HA subjects will follow exercise by performing additional Intestinal Permeability Measurements, providing pre (IP2) and post acclimation (IP3) measurements of intestinal permeability. Day 6 of HA will provide a posttest measurement of subjects' capacity to work in the heat, and will be synonymous with Heat Tolerance Trial 2 (HT2).

Subjects will take quercetin during the seven days of HA in one condition, and placebo in the other. At least 1 month must elapse before a subject will be allowed to repeat the opposite condition. The order will be balanced (half will take quercetin first, the other half placebo). This will be a double blinded study. Neither the investigators nor the subjects will know whether a HA involves quercetin or placebo.

Due to the possibility of outside factors causing variations in intestinal permeability over the course of the study, IP1 will always be used as a baseline condition, with IP2 and IP3 being scored relative (as percent change) to the first. Subjects will never be supplemented in IP1, as this might affect basal measurements of permeability. However, because quercetin supplementation may only exert a transient effect on intestinal permeability, subjects will always be supplemented (with either placebo or quercetin, according to condition) in IP2 and IP3.

In all conditions, subjects will be required to follow guidelines on diet and exercise. They will be instructed to avoid caffeine, alcohol, and to stay well hydrated. They will be instructed to avoid exercise that is not directly outlined by the experiment (see attached). Their meals will be provided by the GCRC to ensure adequate nutrition and to avoid high dietary levels of quercetin. We are currently working with BioNutrition on this menu. To ensure compliance with this diet, subjects will fill out a food diary.

Eligibility criteria: Inclusion Criteria:

* Healthy: 1 or less CV risk factor. Positive risk factors include:

  * Family history
  * Current cigarette smoker or quit within the previous 6 months
  * Hypertension (\>140/90 mmHg) or on antihypertensive medication
  * Impaired fasting glucose (\>110 mg/dl)
  * Dyslipidemia (LDL\>130 mg/dl;HDL\<40 mg/dl, total \>200 mg/dl)
  * Low VO2 peak: \<40ml/kg/min
  * Overfatness(BMI\>30 kg/m2 and/or body fat \> 25%)
* Male
* 18-39 years of age
* Willing to follow study diet
* Willing to exercise for prescribed time
* Willing to tolerate hot environment
* Willing to avoid external influences (ambient heat, uv exposure, external exercise) for study duration

Exclusion Criteria:

* History of heat illness
* Current NSAID use
* Known gastrointestinal disease
* Illness (physician provide physical before subject begin each condition)

Primary outcomes:
measure: Urinary Lactulose Excretion
timeFrame: Baseline
measure: Plasma endotoxin
timeFrame: Baseline
measure: Plasma Quercetin
timeFrame: Baseline
measure: Plasma TNF-a
timeFrame: pre, post, 2hours post, 4 hours post exercise on Day 1 of exercise/heat stress
measure: plasma Il-6
timeFrame: Pre, post, 2hours post, 4 hours post exercise, day 1 of exercise/heat stress
measure: Plasma Il-10
timeFrame: Pre, post, 2 hours post, 4 hours post exercise on Day 1 of exercise/heat stress
measure: HSP70 content of peripheral blood mononuclear cells
timeFrame: Pre, post, 2 hours post, 4 hours post exercise on day 1 of exercise/heat stress
measure: HSF-1 content of peripheral blood mononuclear cells
timeFrame: Pre, post, 2 hours post, 4 hours post exercise on day 1 of exercise/heat stress
measure: Core temperature response to heat tolerance test
timeFrame: heat tolerance test 1= before study onset
measure: Skin temperature response to heat tolerance test
timeFrame: heat tolerance test 1= before study onset
measure: Mean body temperature response to heat tolerance test
timeFrame: heat tolerance test 1= before study onset
measure: Heart rate response to heat tolerance test
timeFrame: heat tolerance test 1= before study onset
measure: Physiological strain response to heat tolerance test
timeFrame: heat tolerance test 1= before study onset
measure: Urinary Lactulose Excretion
timeFrame: Day 1 of exercise/heat stress
measure: Urinary Lactulose Excretion
timeFrame: Day 7 of exercise/heat stress
measure: Plasma Quercetin
timeFrame: Day 1 of exercise/heat stress
measure: Plasma Quercetin
timeFrame: Day 7 of exercise/heat stress
measure: Plasma Endotoxin
timeFrame: Day 1 of exercise/heat stress
measure: plasma endotoxin
timeFrame: day 7 of exercise/heat stress
measure: Plasma TNF-a
timeFrame: pre, post, 2hours post, 4 hours post exercise on Day 7 of exercise/heat stress
measure: plasma Il-10
timeFrame: pre, post, 2hours post, 4 hours post exercise on Day 7 of exercise/heat stress
measure: plasma Il-6
timeFrame: pre, post, 2hours post, 4 hours post exercise on Day 7 of exercise/heat stress
measure: HSP70 content of peripheral blood mononuclear cells
timeFrame: pre, post, 2hours post, 4 hours post exercise on Day 7 of exercise/heat stress
measure: HSF-1 content of peripheral blood mononuclear cells
timeFrame: pre, post, 2hours post, 4 hours post exercise on Day 7 of exercise/heat stress
measure: Core temperature response to heat tolerance test
timeFrame: heat tolerance trial 2 = day 6 of exercise/heat stress
measure: Skin temperature response to heat tolerance test
timeFrame: heat tolerance trial 2 = day 6 of exercise/heat stress
measure: Mean body temperature response to heat tolerance test
timeFrame: heat tolerance trial 2 = day 6 of exercise/heat stress
measure: Heart rate response to heat tolerance test
timeFrame: heat tolerance trial 2 = day 6 of exercise/heat stress
measure: physiological strain response to heat tolerance test
timeFrame: heat tolerance trial 2 = day 6 of exercise/heat stress
Secondary outcomes:
measure: Improvements in sweat rate following heat acclimation exercise
timeFrame: heat tolerance test 1= before study onset
measure: Plasma volume expansion in response to heat acclimation exercise
timeFrame: heat tolerance test 1= before study onset
measure: Improvements in sweat rate following heat acclimation exercise
timeFrame: heat tolerance trial 2 = day 6 of exercise/heat stress
measure: plasma volume expansion in response to heat acclimation exercise
timeFrame: heat tolerance trial 2 = day 6 of exercise/heat stress
Other outcomes:
Locations:
city: Albuquerque
country: United States
facility: UNM General Clinical Research Center
state: New Mexico
Study officials:
affiliation: University of New Mexico, Professor and Chariman, Dpt of Internal Medicine
name: Pope L Moseley, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UNM Department of Health, Exercise and Sports Sciences and UNM Department of Internal Medicine
name: Matthew R. Kuennen, PhD
role: STUDY_DIRECTOR
References: