Clinical trial NCT05618197: Chronic Passive Heating in Healthy Older Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Aging
Keywords: Passive heating
Endothelial function
Heat shock proteins
Cognitive function
Muscle strength
Lead sponsor: University of Portsmouth
Sponsor class: OTHER
First posted: 2022-11-16
Enrollment: 20
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Brachial artery flow-mediated dilation
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Secondary outcomes:
measure: Brachial and carotid artery blood flow velocity
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Carotid vessel diameter
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Carotid intima-media thickness
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Carotid compliance
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Carotid distensibility
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Carotid stiffness
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Microvascular function
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Stroke volume
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Total peripheral resistance
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Cardiac output
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Mean arterial pressure
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Systolic blood pressure
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Diastolic blood pressure
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Intracellular HSP27 concentration
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Intracellular HSP60 concentration
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Intracellular HSP70 concentration
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Intracellular HSP90 concentration
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Plasma eHSP27 concentration
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Plasma eHSP60 concentration
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Plasma eHSP70 concentration
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Plasma eHSP90 concentration
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Reaction time
timeFrame: 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
measure: Logical reasoning
timeFrame: 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
measure: Memory
timeFrame: 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
measure: Cerebral oxygenation
timeFrame: 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
measure: Maximum quadriceps strength
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Maximum grip strength
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Lower extremity function
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Quadriceps muscle electrical activity
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Balance capacity
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Gait characteristics
timeFrame: Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
measure: Total minutes of physical activity (light, moderate, moderate to vigorous physical activity).
timeFrame: 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
measure: Sleep efficiency (time in bed + time asleep)
timeFrame: 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
Other outcomes:
Locations:
city: Portsmouth
country: United Kingdom
facility: Spinnaker Building
state: Hampshire
Study officials:
affiliation: University of Portsmouth
name: Zoe Saynor, PhD
role: STUDY_DIRECTOR
References: