Thermal Tolerance Assessment for Aging Adults

Overseen By Lacy M Alexander, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Penn State University

Must not be taking: Thermoregulatory drugs, Cardiovascular drugs

Disqualifiers: Cancer, Cardiovascular disease, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

190 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine how older adults manage body temperature under varying heat and humidity conditions. Researchers seek to identify the limits of heat stress that older adults can endure before their bodies fail to cool down effectively, potentially leading to heat-related illnesses. Participants will exercise in controlled environments with gradually increasing temperatures and humidity levels. The study will also assess whether taking low-dose aspirin (acetylsalicylic acid) daily for at least a week affects these heat tolerance limits. Ideal participants are healthy adults without disease symptoms or mobility issues affecting light exercise. As an Early Phase 1 trial, this study focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Do I need to stop my current medications for the trial?

You may need to stop taking medications that affect thermoregulatory or cardiovascular responses to exercise, as these are part of the exclusion criteria.

Will I have to stop taking my current medications?

You may need to stop taking medications that affect how your body handles heat or exercise, as these are excluded from the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that low-dose aspirin is usually safe for older adults, and many can take it long-term without issues. One study found that after almost five years, low-dose aspirin did not cause major health problems compared to a placebo. However, a small risk of stomach issues exists, particularly for those who consume alcohol. Experts advise against starting low-dose aspirin to prevent heart disease in individuals over 60 without consulting a doctor. While many tolerate low-dose aspirin well, it's crucial to consider personal health and consult a healthcare provider before beginning its use. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it aims to understand how aging adults tolerate heat, an area with limited current options. The unique approach of this trial involves two experimental methods: exercising under gradually increasing temperature or humidity and the potential influence of low-dose aspirin on thermal tolerance. These methods could uncover vital insights into how older adults can better manage heat stress, potentially informing future guidelines or treatments to enhance their resilience against extreme environmental conditions. By exploring how aspirin might modify heat tolerance, researchers hope to reveal new strategies for protecting aging populations from heat-related health issues.

What evidence suggests that this trial's treatments could be effective for thermoregulation in aging adults?

Research has shown that low-dose aspirin (ASA), which participants in this trial may receive, does not alter core or skin temperature in older adults during heat stress. Studies have found that while low-dose ASA can reduce skin blood flow, it does not impact the body's ability to regulate core temperature in hot or humid conditions. Thus, even though ASA affects skin blood flow, it does not prevent heat stress-related issues. Consequently, low-dose ASA may not help older adults maintain a stable internal temperature in the heat. ^{6 7 8 9 10}

Who Is on the Research Team?

W. Larry Kenney, Ph.D.

Principal Investigator

The Pennsylvania State University

Are You a Good Fit for This Trial?

This trial is for adults aged 18 and older, with a focus on those who are healthy and show no signs of disease. Women must have regular menstrual cycles. Participants over 40 need doctor approval. Excluded are those on certain meds, with exercise restrictions, pregnant women, or with a history of serious diseases like cancer or diabetes.

Inclusion Criteria

I feel fine and show no signs of my condition according to exercise guidelines.

I am a premenopausal woman with regular menstrual cycles.

Exclusion Criteria

I am not on medications that affect my body's response to heat or exercise.

I have a history of Crohn's disease, diverticulitis, or a similar gut condition.

Any contraindications to low intensity physical activity on the Physical Activity Readiness Questionnaire

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Critical Environmental Limits

Subjects perform exercise with increasing ambient temperature or humidity until core temperature begins to rise

2 hours per visit

Multiple visits (in-person)

Aspirin Supplementation

After a minimum of 7 days of daily, low-dose aspirin ingestion, subjects repeat critical environmental limits trials

7 days of aspirin ingestion, followed by 2 hours per visit

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Control
• Low dose ASA

Trial Overview

The study tests how well older adults can handle heat by having them exercise in various temperatures and humidity levels. The goal is to find the environmental limits where aging bodies struggle to regulate temperature, increasing the risk of heat-related illnesses.

How Is the Trial Designed?

Group I: Critical Environmental Limits Experimental Treatment 1 Intervention

Subjects will perform exercise at \~200-300W with ambient temperature or humidity increasing every 5 min throughout the trial until core temperature begins to rise.

Group II: Aspirin Supplementation Experimental Treatment 1 Intervention

After a minimum of 7 days of daily, low-dose aspirin ingestion, older subjects will repeat critical environmental limits trials. As before, subjects will perform exercise at \~200-300W with ambient temperature or humidity increasing every 5 min throughout the trial until core temperature begins to rise.

Who Is Running the Clinical Trial?

Penn State University

Lead Sponsor

Trials

380

Recruited

131,000+

Published Research Related to This Trial

Elderly individuals show reduced thermal adaptation capacities, as evidenced by significantly lower thermal evoked potentials in response to warm environments compared to younger subjects.

The study suggests that this decline in thermal sensitivity may be linked to dysfunction in C-fibers, which are important for sensing temperature changes, indicating a potential mechanism behind altered thermoregulation in aging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Age-related decline in thermal adaptation capacities: an evoked potentials study. Kemp, J., Després, O., Pebayle, T., et al.[2014]

A new technique was used to study how skin and core temperatures respond to cold stimulation during sleep, involving 27 participants over two nights, one with sleep deprivation and one with normal sleep.

The study found that while skin temperature decreased during cold stimulation in both sleep and waking states, the changes were much smaller during sleep, particularly in non-REM sleep compared to REM sleep, indicating reduced thermal sensitivity during sleep.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peripheral thermal responsivity to facial cooling during sleep. Jennings, JR., Reynolds, CF., Bryant, DS., et al.[2019]

In a study involving 23 heat-sensitive individuals with multiple sclerosis (MS) and 19 healthy controls, MS subjects experienced a significantly higher core body temperature after short-term heat exposure in a sauna, indicating increased heat sensitivity.

Following heat exposure, individuals with MS showed immediate declines in physical performance, including walking and balance, compared to controls, but these effects were not prolonged, suggesting that while heat impacts functioning acutely, it does not have lasting effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of heat stress on physical functioning in persons with multiple sclerosis. Romberg, A., Ikonen, A., Ruutiainen, J., et al.[2012]

Mild warming of the skin by 0.4 degrees Celsius significantly improves sleep onset in both healthy elderly individuals and elderly insomniacs, with effects comparable to those seen in younger adults.

Despite the effectiveness of temperature manipulation, elderly individuals, particularly those with insomnia, have a reduced ability to perceive these temperature changes, indicating a potential challenge in recognizing effective sleep aids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diminished capability to recognize the optimal temperature for sleep initiation may contribute to poor sleep in elderly people. Raymann, RJ., Van Someren, EJ.[2022]

A study involving 20 healthy volunteers found that simple aluminum thermal devices can effectively assess thermal sensitivity and pain, showing only minor differences compared to a sophisticated thermotester when avoiding temporal summation of stimuli.

While the simple devices are useful for clinical settings lacking expensive equipment, more advanced tools are still necessary for precise threshold measurements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of orofacial thermal sensitivity assessed with simple devices and sophisticated equipment. Ayranci, M., Koutris, M., Lobbezoo, F., et al.[2019]

In a multicenter clinical trial involving 619 patients with neuropathic pain, the capsaicin 179 mg patch showed that while some patients experienced significant pain relief after the first application, others required up to three applications to achieve a ≥30% reduction in pain intensity.

By 12 months, late responders (those needing multiple applications) achieved similar levels of pain relief, sleep improvement, and quality of life as early responders, indicating that repeated applications can be effective for those who initially do not respond.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progressive Response to Repeat Application of Capsaicin 179 mg (8% w/w) Cutaneous Patch in Peripheral Neuropathic Pain: Comprehensive New Analysis and Clinical Implications. Freynhagen, R., Argoff, C., Eerdekens, M., et al.[2021]

The placebo effect in clinical trials has been increasing, making it harder to demonstrate the effectiveness of treatments that target biological mechanisms, which poses challenges for trial reliability.

By applying insights from placebo and nocebo research, such as the impact of verbal suggestions and emotional expectations, researchers can better understand and manage the variability of placebo effects and improve trial designs to maintain blinding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nocebo vs. placebo: the challenges of trial design in analgesia research. Vase, L., Amanzio, M., Price, DD.[2015]

Older adults have a higher warmth detection threshold compared to younger adults, meaning they may not sense warmth as effectively, which could increase their risk of heat-related illnesses.

Cold detection thresholds are lower in older adults under normal temperature conditions, indicating they may be less sensitive to cold, but this sensitivity does not change significantly under mild hyperthermia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lower thermal sensation in normothermic and mildly hyperthermic older adults. Takeda, R., Imai, D., Suzuki, A., et al.[2018]

The study assessed the reliability of thermal quantitative sensory testing (QST) in 22 healthy volunteers, finding that thermal detection and heat pain thresholds showed good reliability for both group and individual analyses.

Cold pain thresholds had high reliability for group comparisons but exhibited significant variability, making them less suitable for individual assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reliability of thermal quantitative sensory testing of the hand in a cohort of young, healthy adults. Moloney, NA., Hall, TM., O'Sullivan, TC., et al.[2022]

The novel TRPV1 antagonist V116517 significantly increased heat pain detection and tolerance thresholds, demonstrating its efficacy in reducing capsaicin-induced hyperalgesia in a randomized trial with healthy volunteers.

V116517 showed a potent antihyperalgesic effect without causing changes in body temperature or side effects, indicating a favorable safety profile compared to the COX-2 inhibitor celecoxib, which had a different mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, positive-controlled, 3-way cross-over human experimental pain study of a TRPV1 antagonist (V116517) in healthy volunteers and comparison with preclinical profile. Arendt-Nielsen, L., Harris, S., Whiteside, GT., et al.[2021]

Indomethacin (Ind) significantly reduced thermal damage in murine skin when administered before exposure to high temperatures, showing a protective effect against heat injury.

In a study involving mice heated at 44 degrees Celsius, Ind allowed for complete recovery from heat damage in all treated mice, while untreated controls experienced irreversible skin reactions, indicating its potential for clinical applications in hyperthermic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indomethacin reduces the skin thermal damage in hyperthermic treatment of experimental malignant tumors. Ostapenko, VV., Akagi, K., Yamamoto, I., et al.[2013]

In a study involving 144 healthy volunteers, it was found that the expectation of receiving an active drug significantly influenced pain thresholds, with those believing they received the active treatment reporting higher thresholds, highlighting the impact of patient expectations on trial outcomes.

The use of active placebos that induce minor sensations can complicate the interpretation of results in clinical trials, as they create different expectations compared to inert placebos, suggesting that new study designs are needed to better account for these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The hidden effects of blinded, placebo-controlled randomized trials: an experimental investigation. Rief, W., Glombiewski, JA.[2021]

Using active-comparator trials instead of placebo-controlled trials can leave more participants acutely ill, as these trials require larger sample sizes to detect smaller differences between treatments.

The article suggests a trial design that randomizes more participants to the investigational treatment, which could reduce the number of nonresponders while still minimizing the use of placebo, making the study more appealing to participants and ethical review boards.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toward rapproachment in the placebo control debate. A calculated compromise of power. Leon, AC., Solomon, DA.[2007]

The review identified 30 techniques that can enhance placebo effects in pain management, based on an analysis of 169 studies, which could be useful in clinical practice.

A taxonomy was developed that categorizes these techniques into five domains, including patient characteristics and beliefs, practitioner characteristics, healthcare settings, treatment characteristics, and patient-practitioner interactions, providing a structured approach to leverage placebo effects for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What techniques might be used to harness placebo effects in non-malignant pain? A literature review and survey to develop a taxonomy. Bishop, FL., Coghlan, B., Geraghty, AW., et al.[2021]

Experimental manipulations of placebo responses in randomized controlled trials have been shown to effectively reduce high placebo response rates, improving the ability to distinguish between drug effects and placebo.

Techniques that neutralize expectations from both study staff and participants, as well as those that enhance accurate reporting of symptom severity, have proven to be the most effective in achieving this reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What can be done to control the placebo response in clinical trials? A narrative review. Evans, K., Colloca, L., Pecina, M., et al.[2023]

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