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

Trial Summary

What is the purpose of this trial?

This study evaluates critical environmental limits (temperature and humidity) above which older adults are unable to effectively thermoregulate. Participants will exercise in a series of different environmental conditions to identify combinations of temperature and humidity above which age-related physiological changes cause uncompensable heat stress, resulting in increased risk of heat illness.

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.

What data supports the idea that Thermal Tolerance Assessment for Aging Adults is an effective treatment?

The available research does not provide specific data supporting the effectiveness of Thermal Tolerance Assessment for Aging Adults as a treatment. Instead, the studies focus on the placebo effect and its impact on clinical trials, suggesting that patient expectations can influence perceived effectiveness. This means that the belief in receiving an active treatment can lead to improved outcomes, even if the treatment itself is not directly effective. Therefore, while the research highlights the importance of managing expectations in trials, it does not offer direct evidence of the treatment's effectiveness for its intended use. ^{1 2 3 4 5}

What data supports the effectiveness of the drug used in the Thermal Tolerance Assessment for Aging Adults trial?

The research highlights the significant impact of placebo effects in clinical trials, suggesting that patient expectations can influence perceived effectiveness. This implies that the effectiveness of treatments like aspirin (Acetylsalicylic acid) may be enhanced by positive patient expectations, as seen in other studies where placebo effects were substantial. ^{1 2 3 4 5}

What safety data exists for the treatment involving aspirin or similar substances?

The provided research does not contain specific safety data for aspirin or its variants (such as Low dose ASA, Acetylsalicylic acid) in the context of thermal tolerance assessment for aging adults. The studies focus on other substances like TRPV1 antagonist, celecoxib, capsaicin, and indomethacin, none of which directly relate to aspirin or its safety profile in this context. ^{6 7 8 9 10}

Is the treatment 'Control' (Placebo, Standard Care) promising for helping older adults with thermal tolerance?

The treatment 'Control' (Placebo, Standard Care) is promising because it helps us understand how older adults respond to temperature changes. This understanding can lead to better ways to improve their comfort and sleep quality, as older adults often have reduced sensitivity to temperature changes, which can affect their sleep and overall well-being. ^{11 12 13 14 15}

How does the placebo treatment in the Thermal Tolerance Assessment for Aging Adults differ from other treatments?

The placebo treatment in this trial serves as a control to compare against any active interventions, focusing on standard care without additional therapeutic effects. This approach helps researchers understand the natural progression of thermal tolerance in aging adults without the influence of new treatments. ^{11 12 13 14 15}

Research Team

W. Larry Kenney, Ph.D.

Principal Investigator

The Pennsylvania State University

Eligibility Criteria

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.

I am 18 or older. If I'm 40+, a doctor has approved my participation.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. United States pubmed.ncbi.nlm.nih.gov

Nocebo vs. placebo: the challenges of trial design in analgesia research. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

Toward rapproachment in the placebo control debate. A calculated compromise of power. [2007]

4. England 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. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

What can be done to control the placebo response in clinical trials? A narrative review. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Comparison of orofacial thermal sensitivity assessed with simple devices and sophisticated equipment. [2019]

7. England 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. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Reliability of thermal quantitative sensory testing of the hand in a cohort of young, healthy adults. [2022]

9. Greece pubmed.ncbi.nlm.nih.gov

Indomethacin reduces the skin thermal damage in hyperthermic treatment of experimental malignant tumors. [2013]

10. United States 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. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Age-related decline in thermal adaptation capacities: an evoked potentials study. [2014]

12. United States pubmed.ncbi.nlm.nih.gov

Peripheral thermal responsivity to facial cooling during sleep. [2019]

13. Netherlands pubmed.ncbi.nlm.nih.gov

The effects of heat stress on physical functioning in persons with multiple sclerosis. [2012]

14. United States pubmed.ncbi.nlm.nih.gov

Diminished capability to recognize the optimal temperature for sleep initiation may contribute to poor sleep in elderly people. [2022]

15. Germany pubmed.ncbi.nlm.nih.gov

Lower thermal sensation in normothermic and mildly hyperthermic older adults. [2018]