Text Size

Effect of Combined Exercise, Heat, and Quercetin Supplementation on Whole Body Stress Response

This study has been completed.
Sponsor:
Collaborators:
Gatorade Sports Science Institute
Quercegen Pharma LLC
Nash Finch Company
Information provided by:
University of New Mexico
ClinicalTrials.gov Identifier:
NCT01168739
First received: July 20, 2010
Last updated: July 21, 2010
Last verified: July 2010
History of Changes
  Purpose

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.


Condition Intervention
Heat Acclimation and Thermotolerance
 Dietary Supplement: Quercetin
Dietary Supplement: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effect of Combined Exercise, Heat, and Quercetin Supplementation on Whole Body Stress Response

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of New Mexico:

Primary Outcome Measures:
  • Urinary Lactulose Excretion [ Time Frame: Baseline ] [ Designated as safety issue: No ]

    Lactulose is a large molecule (disaccharide: 242 kDa) that should not be permeable to the gastrointestinal barrier under normal conditions.

    Subjects will ingest a test solution containing 10 g lactulose (Quintron Instrument Company, QT02500-10-5, Milwaukee, WI, USA) dissolved in 50 ml of distilled water. This is followed by 8 hour urine collection.


  • Plasma endotoxin [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Plasma endotoxin will be detected with a standard limulus amebocyte lysate (LAL) kit (Cell Sciences, HIT302, Canton, MA, USA). The minimum and maximum detection limits of this kit are 1.4 pg/ml and 1,000 pg/ml, respectively.

  • Plasma Quercetin [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Quercetin conjugates are hydrolysized from plasma with B-glucuronidase and arylsulfatase kit (Roche Diagnostics, 10127698001, Indianapolis, IN, USA). The resulting supernatant is applied to solid phase extraction cartridges and run through a vacuum manifold for purification. The eluent is 80% methanol / 20% 18 MOhm water. Following solid phase extraction chromatographic analysis is performed using high performance liquid chromatography (HPLC).

  • Plasma TNF-a [ Time Frame: pre, post, 2hours post, 4 hours post exercise on Day 1 of exercise/heat stress ] [ Designated as safety issue: No ]
  • plasma Il-6 [ Time Frame: Pre, post, 2hours post, 4 hours post exercise, day 1 of exercise/heat stress ] [ Designated as safety issue: No ]
  • Plasma Il-10 [ Time Frame: Pre, post, 2 hours post, 4 hours post exercise on Day 1 of exercise/heat stress ] [ Designated as safety issue: No ]
  • HSP70 content of peripheral blood mononuclear cells [ Time Frame: Pre, post, 2 hours post, 4 hours post exercise on day 1 of exercise/heat stress ] [ Designated as safety issue: No ]
  • HSF-1 content of peripheral blood mononuclear cells [ Time Frame: Pre, post, 2 hours post, 4 hours post exercise on day 1 of exercise/heat stress ] [ Designated as safety issue: No ]
  • Core temperature response to heat tolerance test [ Time Frame: heat tolerance test 1= before study onset ] [ Designated as safety issue: No ]
  • Skin temperature response to heat tolerance test [ Time Frame: heat tolerance test 1= before study onset ] [ Designated as safety issue: No ]
  • Mean body temperature response to heat tolerance test [ Time Frame: heat tolerance test 1= before study onset ] [ Designated as safety issue: No ]
  • Heart rate response to heat tolerance test [ Time Frame: heat tolerance test 1= before study onset ] [ Designated as safety issue: No ]
  • Physiological strain response to heat tolerance test [ Time Frame: heat tolerance test 1= before study onset ] [ Designated as safety issue: No ]
  • Urinary Lactulose Excretion [ Time Frame: Day 1 of exercise/heat stress ] [ Designated as safety issue: No ]
  • Urinary Lactulose Excretion [ Time Frame: Day 7 of exercise/heat stress ] [ Designated as safety issue: No ]
  • Plasma Quercetin [ Time Frame: Day 1 of exercise/heat stress ] [ Designated as safety issue: No ]
  • Plasma Quercetin [ Time Frame: Day 7 of exercise/heat stress ] [ Designated as safety issue: No ]
  • Plasma Endotoxin [ Time Frame: Day 1 of exercise/heat stress ] [ Designated as safety issue: No ]
  • plasma endotoxin [ Time Frame: day 7 of exercise/heat stress ] [ Designated as safety issue: No ]
  • Plasma TNF-a [ Time Frame: pre, post, 2hours post, 4 hours post exercise on Day 7 of exercise/heat stress ] [ Designated as safety issue: No ]
  • plasma Il-10 [ Time Frame: pre, post, 2hours post, 4 hours post exercise on Day 7 of exercise/heat stress ] [ Designated as safety issue: No ]
  • plasma Il-6 [ Time Frame: pre, post, 2hours post, 4 hours post exercise on Day 7 of exercise/heat stress ] [ Designated as safety issue: No ]
  • HSP70 content of peripheral blood mononuclear cells [ Time Frame: pre, post, 2hours post, 4 hours post exercise on Day 7 of exercise/heat stress ] [ Designated as safety issue: No ]
  • HSF-1 content of peripheral blood mononuclear cells [ Time Frame: pre, post, 2hours post, 4 hours post exercise on Day 7 of exercise/heat stress ] [ Designated as safety issue: No ]
  • Core temperature response to heat tolerance test [ Time Frame: heat tolerance trial 2 = day 6 of exercise/heat stress ] [ Designated as safety issue: No ]
  • Skin temperature response to heat tolerance test [ Time Frame: heat tolerance trial 2 = day 6 of exercise/heat stress ] [ Designated as safety issue: No ]
  • Mean body temperature response to heat tolerance test [ Time Frame: heat tolerance trial 2 = day 6 of exercise/heat stress ] [ Designated as safety issue: No ]
  • Heart rate response to heat tolerance test [ Time Frame: heat tolerance trial 2 = day 6 of exercise/heat stress ] [ Designated as safety issue: No ]
  • physiological strain response to heat tolerance test [ Time Frame: heat tolerance trial 2 = day 6 of exercise/heat stress ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Improvements in sweat rate following heat acclimation exercise [ Time Frame: heat tolerance test 1= before study onset ] [ Designated as safety issue: No ]
  • Plasma volume expansion in response to heat acclimation exercise [ Time Frame: heat tolerance test 1= before study onset ] [ Designated as safety issue: No ]
  • Improvements in sweat rate following heat acclimation exercise [ Time Frame: heat tolerance trial 2 = day 6 of exercise/heat stress ] [ Designated as safety issue: No ]
  • plasma volume expansion in response to heat acclimation exercise [ Time Frame: heat tolerance trial 2 = day 6 of exercise/heat stress ] [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: September 2009
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Quercetin
not necessary, contained in protocol
 Dietary Supplement: Quercetin
2g/d dietary quercetin supplementation, 1g taken am; 1g taken pm
Placebo Comparator: Placebo
not necessary, contained in protocol
 Dietary Supplement: Placebo
Placebo, performed on same subjects as Quercetin Arm, used to compare results between conditions

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

Ages Eligible for Study:   18 Years to 39 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01168739

Locations
United States, New Mexico
UNM General Clinical Research Center
Albuquerque, New Mexico, United States, 87131
Sponsors and Collaborators
University of New Mexico
Gatorade Sports Science Institute
Quercegen Pharma LLC
Nash Finch Company
Investigators
Principal Investigator: Pope L Moseley, MD University of New Mexico, Professor and Chariman, Dpt of Internal Medicine
Study Director: Matthew R. Kuennen, PhD UNM Department of Health, Exercise and Sports Sciences and UNM Department of Internal Medicine
  More Information

No publications provided

Responsible Party: Pope Moseley, Professor and Chairman, University of New Mexico, Department of Internal Medicine
ClinicalTrials.gov Identifier: NCT01168739     History of Changes
Other Study ID Numbers: HRRC08-606
Study First Received: July 20, 2010
Last Updated: July 21, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by University of New Mexico:
thermotolerance
heat acclimation
quercetin
exertional heat illness
gastrointestinal barrier permeability

Additional relevant MeSH terms:
Quercetin
Antioxidants
Molecular Mechanisms of Pharmacological Action
 Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 16, 2013