AzTrials
AzTrials

Endothelial DysfunctionNCT04588103

Artery Function Responses to Heat Therapy and Exercise Training

A study testing Heat therapy and Exercise training in people with Endothelial Dysfunction, run by McMaster University at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study will explore the effects of 8 weeks of local leg heat therapy, exercise training, or both on measures of vascular function, cardiorespiratory fitness, and muscle strength in young, healthy individuals. Read more about this study

Who is it for?
Ages 18 to 35 yearsHealthy volunteers can take part
Conditions the study is for
Endothelial Dysfunction
What is being tested?
Heat therapy and Exercise training
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteCanada
Study dates
13 Jul 2021to 18 Jun 2022
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 35 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Apparently healthy (i.e., no cardiovascular, musculoskeletal, or metabolic disease)
  • 18-35 years old
  • Recreationally and/or physically active

Who cannot join

  • History of cardiovascular, musculoskeletal, or metabolic disease
  • Regular smoking and/or vasoactive drug use

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • McMaster University Vascular Dynamics Lab

    Hamilton, Ontario, L8S 4L8

Other trials in Canada

About this study

Official title: The Effects of 8 Weeks of Lower Limb Heat Therapy, Moderate-intensity Cycling Exercise, or Both on Vascular Function in Young, Healthy Males and Females

This study will explore the effects of 8 weeks of local leg heat therapy, exercise training, or both on measures of vascular function, cardiorespiratory fitness, and muscle strength in young, healthy individuals. Participants will be allocated into either a control group that will maintain their regular physical activity habits; or into one of three training groups: heat therapy will involve lower limb warm water immersion, exercise training will involve moderate-intensity cycling, and combined training will involve both performed in sequential order.

Read the detailed description

A between-groups interventional design will be used in a cohort of 80 young, healthy males and females 18-35 years old. Interested individuals will be invited to the lab for a screening and familiarization visit (1 hr), in which participants will be introduced to various lab testing protocols to ensure proper performance and tolerance during experimental data collection sessions. Participants will be randomized into one of four groups for an 8-week intervention period: (1) no training (CON), (2) lower limb heat therapy (HEAT), (3) moderate intensity cycling training (EX), or (4) combined training (HEATEX). CON will involve maintenance of regular physical activity habits. HEAT will involve 45 minutes of lower limb hot water immersion (42 °C) using a custom-made heating apparatus 3x/week. EX will involve of 45 minutes of cycling on an ergometer at 40-59% VO2reserve 3x/week. HEATEX will require participants to perform 3x/week of exercise training and heat therapy consecutively and in that order, such that each session is 90 minutes in duration. In total, all groups except CON will be expected to complete 24 intervention sessions. Vascular function will be characterized by measures of endothelial function, arterial stiffness, arterial structure, central hemodynamics, arterial blood flow and shear, and endothelial cell nitric oxide production. Muscle and metabolic adaptations will be characterized by measures of cardiorespiratory fitness, body composition, muscle strength and thickness, and fasting glucose and insulin. Inflammatory profile will be characterized by concentrations of interleukins, heat shock proteins, and cortisol. Thermal physiological adaptations will be characterized by measures of core and skin temperature and sweat rate. Perceptual responses will be characterized by measures of thermal comfort and sensation, calmness, alertness, mood, affect, and ratings of perceived exertion. Intervention adherence will be tracked throughout the intervention period. For the acute investigation (3-hr visit), outcome measures will be assessed before and immediately following the first and last training session. For the chronic investigation (2-hr visit), outcome measures will be assessed at weeks 0, 2, 4, 6, and 8 of the intervention period.

Being tested
Heat therapy, Exercise training
Keywords
heat therapy, exercise training, endothelial function
Medical subject headings
Hyperthermia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Heat therapyOther

    Lower limb warm water immersion (42 degrees C)

  • Exercise trainingOther

    Moderate-intensity cycling exercise (~40-59% VO2 reserve)

Study groups in NCT04588103
Study groupRoleWhat they receive
ControlNo interventionParticipants will be asked to maintain their regular physical activity habits for the duration of the 8-week intervention period.
Heat therapyExperimentalParticipants will be asked to undergo 45 minutes of lower limb hot water immersion (42 degrees C) 3 times per week for 8 weeks.
Receives: Other: Heat therapy
Exercise trainingExperimentalParticipants will be asked to undergo 45 minutes of moderate-intensity cycling exercise (~40-59% VO2 reserve) 3 times per week for 8 weeks.
Receives: Other: Exercise training
Combined trainingExperimentalParticipants will be asked to undergo 90 minutes of moderate-intensity cycling exercise and lower limb hot water immersion sequentially 3 times per week for 8 weeks.
Receives: Other: Heat therapy; Other: Exercise training

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Brachial artery endothelial function

    Flow-mediated dilation (FMD) is a measure of the ability of the artery to dilate in response to elevated shear stress, and represents endothelial function. For this technique, a pressure cuff will be wrapped around the forearm and then inflated to ~200 mmHg for 5 minutes to occlude blood flow through the artery site. Doppler ultrasound (Vivid q, GE Medical Systems, Horten, Norway) and a 12 MHz linear array probe will be used to measure artery diameter before cuff inflation (rest), before cuff deflation (ischemia), and for three minutes after cuff deflation (reactive hyperemia). Images of the BA will be collected in Duplex mode and obtained proximal to the antecubital fossa. FMD will be calculated using this formula: FMD% = ((peak diameter-baseline diameter)/baseline diameter) × 100%.

    Measured: Change in endothelial function from week 0 to 8

  2. Arterial stiffness

    Pulse wave velocity (PWV) is a measure of the speed at which a pulse travels between two superficial artery sites, and represents arterial stiffness. For this outcome, applanation tonometers (i.e., micromanometer-tipped probes) (SPT-301, Millar Instruments, Houston, Texas, USA) will be used to detect and transmit pulse pressure wave forms at the carotid, femoral, and dorsalis pedis or tibialis posterior arteries. PWV will be calculated between the carotid-femoral arteries and femoral-foot arteries to quantify central and peripheral arterial stiffness, respectively, using this general formula: PWV = distance/pulse transit time.

    Measured: Change in arterial stiffness from week 0 to 8

Secondary outcomes (7)

  1. Cardiorespiratory fitness

    VO2peak represents the maximum rate of oxygen consumption that the body can attain, and is reliant on both oxygen delivery to muscles and oxygen utilization by muscles. In this VO2peak test, participants will cycle on a cycle ergometer (Excalibur Lode B.V., Groningen, The Netherlands) at an intensity that begins at 50 W and progressively increases at a rate of 1 W every 2 seconds until volitional exhaustion or a pedaling cadence < 60 rpm. A mask equipped with a breath-by-breath gas analyzer (Quark CPET, COSMED, Rome, Italy) will be worn to obtain the ratio of CO2 produced to O2 consumed, and a HR monitor (Polar Electro Oy, Kempele, Finland) will be worn to monitor HR throughout the duration of the test. VO2peak will be calculated using this formula: VO2peak = (VI * FIO2) - (VE * FEO2).

    Measured: Change in cardiorespiratory fitness from week 0 to 8

  2. Body composition

    Body composition tests measure the proportions of fat mass and fat-free mass in the body. Participants will have their body composition assessed through air displacement plethysmography (BodPod). This method is non-invasive and involves ~5 minutes of sitting still and quietly as the measurement is completed.

    Measured: Change in body composition from week 0 to 8

  3. Muscle strength

    Knee extensor muscle strength will be assessed with an isokinetic dynamometer (Biodex). Participants will be familiarized with the testing procedures before assessment. Participants will be seated with restraining straps secured over the trunk, pelvis, and thigh; arms will be crossed over their chest. The axis of the dynamometer will be aligned with the axis of rotation of the knee joint. Participants will be asked to kick out repeatedly against the arm of the machine, and the force produced will be recorded.

    Measured: Change in muscle strength from week 0 to 8

  4. Metabolic blood markers

    Fasting insulin and glucose will be measured in blood plasma and serum.

    Measured: Change in metabolic markers from week 0 to 8

  5. Core temperature

    Core temperature will be measured using a wireless telemetric pill during the acute experimental testing visits, and tympanic and rectal thermometry during all experimental testing visits. Participants will be instructed to swallow the pill with water 2-3 hours prior to each testing session.

    Measured: Change in core temperature from week 0 to 8

  6. Endothelial cell nitric oxide production markers

    Endothelial nitric oxide synthase protein content and activity, and nitric oxide and superoxide anion production will be measured in human umbilical vein endothelial cell cultures bathed in serum collected from the study.

    Measured: Change in endothelial nitric oxide production from week 0 to 8

  7. Heat shock protein mRNA and content

    HSP72 and HSP90 will be measured in blood plasma and serum.

    Measured: Change in heat shock proteins from week 0 to 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Oct 2020
  2. Study start13 Jul 2021
  3. Primary completion18 Jun 2022
  4. Study completion18 Jun 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04588103
Sponsor's protocol ID
HEATEX
Status last verified
Nov 2022
First submitted
2 Oct 2020
Last updated
9 Nov 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Cheng JL, MacDonald MJ. Effect of heat stress on vascular outcomes in humans. J Appl Physiol (1985). 2019 Mar 1;126(3):771-781. doi: 10.1152/japplphysiol.00682.2018. Epub 2019 Jan 24.

    PubMed 30676869

  • Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007 Mar 13;115(10):1285-95. doi: 10.1161/CIRCULATIONAHA.106.652859. No abstract available.

    PubMed 17353456

  • Gimbrone MA Jr, Garcia-Cardena G. Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis. Circ Res. 2016 Feb 19;118(4):620-36. doi: 10.1161/CIRCRESAHA.115.306301.

    PubMed 26892962

  • Heinonen I, Laukkanen JA. Effects of heat and cold on health, with special reference to Finnish sauna bathing. Am J Physiol Regul Integr Comp Physiol. 2018 May 1;314(5):R629-R638. doi: 10.1152/ajpregu.00115.2017. Epub 2017 Dec 20.

    PubMed 29351426

  • Miyata M, Tei C. Waon therapy for cardiovascular disease: innovative therapy for the 21st century. Circ J. 2010 Apr;74(4):617-21. doi: 10.1253/circj.cj-09-0939. Epub 2010 Feb 13.

    PubMed 20154403

  • Serbulea M, Payyappallimana U. Onsen (hot springs) in Japan--transforming terrain into healing landscapes. Health Place. 2012 Nov;18(6):1366-73. doi: 10.1016/j.healthplace.2012.06.020. Epub 2012 Jul 17.

    PubMed 22878276

  • Thijssen DHJ, Bruno RM, van Mil ACCM, Holder SM, Faita F, Greyling A, Zock PL, Taddei S, Deanfield JE, Luscher T, Green DJ, Ghiadoni L. Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans. Eur Heart J. 2019 Aug 7;40(30):2534-2547. doi: 10.1093/eurheartj/ehz350.

    PubMed 31211361

  • Van Bortel LM, Laurent S, Boutouyrie P, Chowienczyk P, Cruickshank JK, De Backer T, Filipovsky J, Huybrechts S, Mattace-Raso FU, Protogerou AD, Schillaci G, Segers P, Vermeersch S, Weber T; Artery Society; European Society of Hypertension Working Group on Vascular Structure and Function; European Network for Noninvasive Investigation of Large Arteries. Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity. J Hypertens. 2012 Mar;30(3):445-8. doi: 10.1097/HJH.0b013e32834fa8b0.

    PubMed 22278144

  • Bailey TG, Cable NT, Miller GD, Sprung VS, Low DA, Jones H. Repeated Warm Water Immersion Induces Similar Cerebrovascular Adaptations to 8 Weeks of Moderate-Intensity Exercise Training in Females. Int J Sports Med. 2016 Sep;37(10):757-65. doi: 10.1055/s-0042-106899. Epub 2016 Jun 10.

    PubMed 27286178

  • Brunt VE, Eymann TM, Francisco MA, Howard MJ, Minson CT. Passive heat therapy improves cutaneous microvascular function in sedentary humans via improved nitric oxide-dependent dilation. J Appl Physiol (1985). 2016 Sep 1;121(3):716-23. doi: 10.1152/japplphysiol.00424.2016. Epub 2016 Jul 14.

    PubMed 27418688

  • Brunt VE, Howard MJ, Francisco MA, Ely BR, Minson CT. Passive heat therapy improves endothelial function, arterial stiffness and blood pressure in sedentary humans. J Physiol. 2016 Sep 15;594(18):5329-42. doi: 10.1113/JP272453. Epub 2016 Jun 30.

    PubMed 27270841

  • Carter HH, Spence AL, Atkinson CL, Pugh CJ, Naylor LH, Green DJ. Repeated core temperature elevation induces conduit artery adaptation in humans. Eur J Appl Physiol. 2014 Apr;114(4):859-65. doi: 10.1007/s00421-013-2817-2. Epub 2014 Jan 8.

    PubMed 24399113

  • Gurovich AN, Braith RW. Enhanced external counterpulsation creates acute blood flow patterns responsible for improved flow-mediated dilation in humans. Hypertens Res. 2013 Apr;36(4):297-305. doi: 10.1038/hr.2012.169. Epub 2012 Oct 18.

    PubMed 23076403

  • Hesketh K, Shepherd SO, Strauss JA, Low DA, Cooper RJ, Wagenmakers AJM, Cocks M. Passive heat therapy in sedentary humans increases skeletal muscle capillarization and eNOS content but not mitochondrial density or GLUT4 content. Am J Physiol Heart Circ Physiol. 2019 Jul 1;317(1):H114-H123. doi: 10.1152/ajpheart.00816.2018. Epub 2019 May 10.

    PubMed 31074654

  • Hoekstra SP, Bishop NC, Faulkner SH, Bailey SJ, Leicht CA. Acute and chronic effects of hot water immersion on inflammation and metabolism in sedentary, overweight adults. J Appl Physiol (1985). 2018 Dec 1;125(6):2008-2018. doi: 10.1152/japplphysiol.00407.2018. Epub 2018 Oct 18.

    PubMed 30335579

Questions about this trial

What is this clinical trial studying?

A study testing Heat therapy and Exercise training in people with Endothelial Dysfunction, run by McMaster University at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Brachial artery endothelial function (time frame: Change in endothelial function from week 0 to 8). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04588103, which also lists 20 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in