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Clinical Trials/NCT05618197
NCT05618197
Completed
Not Applicable

The Effects of Chronic Passive Heating on Vascular Function, Cognitive Function, Muscle Function and Heat Shock Protein Responses in Middle-aged to Older Adults: A Randomised, Controlled Crossover Trial

University of Portsmouth1 site in 1 country19 target enrollmentMay 23, 2023
ConditionsAging

Overview

Phase
Not Applicable
Intervention
Not specified
Conditions
Aging
Sponsor
University of Portsmouth
Enrollment
19
Locations
1
Primary Endpoint
Brachial artery flow-mediated dilation
Status
Completed
Last Updated
8 months ago

Overview

Brief Summary

Aging is associated with a decline in cardiovascular health, cognitive function and losses in muscle strength, with half or more of those over age 65 suffering from two or more comorbidities (e.g., heart disease, type 2 diabetes). The worldwide population of older adults is growing rapidly, with one in six people expected to be over age 65 by 2050. This will place further financial burden from chronic diseases on already stressed healthcare systems. While studies show that frequent exercise is an effective way for older adults to maintain or improve cardiovascular and metabolic health, older individuals are less physically active and do not adhere well to exercise programs, often due to physical or medical limitations. Therefore, alternative methods for older adults to get the same health benefits as exercise require further exploration. Recent work has shown that passive heat therapy may be one such alternative solution.

Detailed Description

Aging is associated with declines in cardiovascular health and cognitive function as well as chronic inflammation and the development of neurodegenerative conditions such as Alzheimer's and Parkinson's disease. Additionally, ageing results in a loss of muscle size and strength, commonly referred to as sarcopenia, leading to increased risk of falls or adverse exercise-related events. It is well understood that frequent exercise improves cardiovascular and metabolic health whilst lowering the risk of disease and all-cause mortality, acting as a treatment for many different health conditions. Despite the evidence of its efficacy, many individuals struggle with adherence to exercise programmes, particularly older adults and clinical populations, with many individuals within these populations unable to perform exercise due to physical limitations or medical contraindications. With one in six people expected to be over the age of 65 years by 2050 and corresponding increases in non-communicable diseases (e.g., cancer, diabetes, cardiovascular disease) anticipated from this aging population, the development of adjunct treatments or alternatives to exercise to improve general health in older populations is needed. Recent work has shown that a potential solution could be the use of passive heat therapy (PHT) (e.g., hot water immersion, sauna), which can achieve health benefits comparable to exercise. Previous work by Brunt and colleagues using eight weeks of chronic heat therapy has demonstrated systemic macro- and microvascular adaptations in young, healthy individuals including improved endothelial function, reduced arterial stiffness and cutaneous vascular conductance. Chronic passive heat acclimation in young, healthy adults has also been shown to improve working memory. Additional studies have shown that ten weeks of passive heating improved muscle strength in middle-aged men and ten days of daily pulsed shortwave diathermy attenuated immobilization-induced muscle atrophy in young, healthy adults. One potential mechanism for the physiological benefits obtained from PHT is the increase of cytoprotective heat shock proteins (HSP) (specifically HSP27, HSP60, HSP70 and HSP90) intracellularly (i) and extracellularly (e) in response to increases in deep body temperature. Increases in the expression of these HSPs have been shown to play a role in reducing inflammation and protecting the vasculature via increases in endothelial nitric oxide synthase activity. Increased HSP concentrations may also prevent the accumulation of harmful biomarkers in the brain that play a role in cognitive decline and development of neurodegenerative diseases. Aging, however, is associated with a reduction in HSP transcription activity in various tissues, resulting in an impaired heat shock response and development of a pro-inflammatory state. Previous work using acute hot water immersion has shown increases in eHSP70. The only study to test the effects of chronic hot water immersion on resting iHSP70 showed no effect, however, the magnitude of stimulus (39°C water) applied by Hoekstra and colleagues and the resultant changes in core temperature were likely too low to induce any changes in HSPs. These studies provide promising evidence that health benefits from PHT similar to those from exercise could translate to older adults. However, most studies testing the effects of PHT on humans have been performed in young, healthy adults, whereas older individuals are likely to derive the greatest benefit from any positive effects of PHT. To date, no study has examined the longer-term effects of PHT on macrovascular, microvascular, cognitive or muscle function, or HSPs in older adults. Therefore, further research is needed to confirm that heat therapy confers the same beneficial health adaptations in older adults.

Registry
clinicaltrials.gov
Start Date
May 23, 2023
End Date
June 6, 2025
Last Updated
8 months ago
Study Type
Interventional
Study Design
Crossover
Sex
All

Investigators

Responsible Party
Principal Investigator
Principal Investigator

Ant Shepherd

Senior Lecturer

University of Portsmouth

Eligibility Criteria

Inclusion Criteria

  • Male or female age ≥ 55
  • Free from cardiometabolic disease
  • Body mass index of 18-35 kg/m2
  • Receipt of a normal 12-lead ECG approved by the School Independent Medical Officer
  • Capacity to understand and provide their written, informed consent to participate in the study protocol

Exclusion Criteria

  • Unable to understand or cooperate with the study protocol due to learning difficulties or otherwise
  • Any current, or past medical (last five years), history of any cardiovascular, respiratory, cancer, renal, hepatic, gastrointestinal, haematological, lymphatic, neurological, psychiatric, or any other disease or diseases.
  • Any regular medication for the last five years (not including acute courses of treatment of less than one month for discrete, resolved conditions).
  • Medications that may influence physiological responses to the passive heating intervention Uncontrolled hypertension (≥ 150 mmHg systolic and/or ≥ 90 mmHg diastolic)
  • Body mass index of \> 35 kg/m2
  • Recent long-term exposure to a hot climate (within the previous three months)
  • Current smoker (or have stopped smoking within the previous three months)

Outcomes

Primary Outcomes

Brachial artery flow-mediated dilation

Time Frame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms

Percentage change from baseline in brachial artery diameter assessed by ultrasound.

Secondary Outcomes

  • Carotid intima-media thickness(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Carotid compliance(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Diastolic blood pressure(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Carotid vessel diameter(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Intracellular HSP70 concentration(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Intracellular HSP90 concentration(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Plasma eHSP60 concentration(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Maximum grip strength(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Total minutes of physical activity (light, moderate, moderate to vigorous physical activity).(Pre and during the final week of 6 weeks of passive heating and pre and during the final week of 6 weeks no intervention with 6 weeks washout between arms)
  • Microvascular function(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Cardiac output(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Mean arterial pressure(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Memory(Pre and post 6 weeks of the passive heating intervention during the first and final heating visits at time points of pre-hot water immersion, 0 hours post and 3 hours post hot water immersion)
  • Quadriceps muscle electrical activity(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Brachial and carotid artery blood flow velocity(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Total peripheral resistance(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Intracellular HSP27 concentration(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Balance capacity(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Carotid distensibility(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Carotid stiffness(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Stroke volume(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Systolic blood pressure(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Intracellular HSP60 concentration(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Plasma eHSP70 concentration(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Plasma eHSP90 concentration(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Maximum quadriceps strength(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Gait characteristics(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Plasma eHSP27 concentration(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Reaction time(Pre and post 6 weeks of the passive heating intervention during the first and final heating visits at time points of pre-hot water immersion, 0 hours post and 3 hours post hot water immersion)
  • Logical reasoning(Pre and post 6 weeks of the passive heating intervention during the first and final heating visits at time points of pre-hot water immersion, 0 hours post and 3 hours post hot water immersion)
  • Cerebral oxygenation(Pre and post 6 weeks of the passive heating intervention during the first and final heating visits at time points of pre-hot water immersion, 0 hours post and 3 hours post hot water immersion)
  • Lower extremity function(Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms)
  • Sleep efficiency (time in bed + time asleep)(Pre and during the final week of 6 weeks of passive heating and pre and during the final week of 6 weeks no intervention with 6 weeks washout between arms)

Study Sites (1)

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