PreDiabetesHOTFUNNCT05070741
Heat Shock Therapy to Improve Mitochondrial Function in Neuropathy
A study testing Heat Therapy in people with PreDiabetes and Neuropathy, run by University of Kansas Medical Center at 1 site in United States.
Trial summary
Sensory dysfunction as a result of peripheral nerve damage is a significant problem that leads to reduced quality of life for patients. The prevalence of sensory dysfunction in peripheral neuropathy associates with epidemic increases in prediabetes and diabetes, but also is relevant to chemotherapy treatments and… Read more about this study
- Who is it for?
- Ages 45 to 75 years
- Conditions the study is for
- PreDiabetes, Neuropathy
- What is being tested?
- Heat Therapy
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jul 2020to 11 Jul 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 45 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- both males and females,
- ages 45-75,
- have suspected or diagnosed prediabetes with or without neuropathy (to be confirmed at pre-intervention evaluation).
Who cannot join
- skin conditions, circulatory insufficiency, or open wounds in the leg that would interfere with healing from a biopsy;
- stroke or other significant nervous system pathology;
- lidocaine allergy;
- anticipated difficulty with blood clotting due to disorder or use of a blood thinner such as Coumadin, Xarelto, or Eliquis;
- use of any medication used to treat abnormal blood glucose such as Metformin;
- body weight > 350 lbs.;
Show all 13Show fewer
- history of anemia or vitamin b12 deficiency;
- clinical anemia (hematocrit <32 for women, <36 for men);
- abnormal SPEP result;
- history of cancer or chemotherapy treatment;
- current or recent use (within the last 6 months) of artificial fingernails / nail enhancements that would interfere with quantitative sensory testing;
- no special classes of subjects such as fetuses, neonates, pregnant women, prisoners, institutionalized individuals, non-English speaking individuals, or other who may be considered vulnerable populations will be included in this study.
- Withdrawal/Termination criteria: Prediabetes will be determined using the American Diabetes Association (ADA) Diabetes Management Guidelines. The subject will meet the criteria for a diagnosis of pre-diabetes if the subject has one or more positive test(s) for either A1c (5.7-6.4%), fasting glucose (100-125 mg/dl), or 2-hr oral glucose tolerance test (140-199 mg/dl). If at pre-intervention evaluation, the subject does not meet the criteria for prediabetes (lower than the above-mentioned range), meets the ADA criteria for diabetes (higher than the above-mentioned range), the subject will be considered a screen fail and will not progress to skin biopsy or intervention.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Kansas Medical Center
Kansas City, Kansas, 66160
About this study
Sensory dysfunction as a result of peripheral nerve damage is a significant problem that leads to reduced quality of life for patients. The prevalence of sensory dysfunction in peripheral neuropathy associates with epidemic increases in prediabetes and diabetes, but also is relevant to chemotherapy treatments and genetic disorders. Clinical approaches to treat peripheral neuropathy and to stimulate axon growth in settings of peripheral axon loss are limited. Although new drugs will hopefully be forthcoming, the most promising approaches likely involve behavioral and lifestyle interventions. Mitochondrial dysfunction is emerging as a key cellular contribution to peripheral axon health and peripheral neuropathy. Mitochondrial deficiencies contribute to neuropathy and include impaired mitochondrial problems with trafficking, mitophagy, fission, and biogenesis. All of these are thought to lead to a bioenergetic crisis, ending in distal axonal degeneration, sensory dysfunction and pain. Heat shock proteins play a critically important role in cellular homeostasis and increasing heat shock protein functions within cells leads to a range of positive improvements, particularly in mitochondria. In addition, new evidence suggests that increasing heat shock protein responses in peripheral nerves has powerful, positive impacts on sensory function and neuropathy.
Our interdisciplinary team will investigate the role of mitochondrial dysfunction in peripheral neuropathy and translate these approaches to improve treatment for patients with peripheral neuropathy. The investigators hypothesize that novel heat treatment interventions that improve mitochondrial function will improve metabolic symptoms and peripheral nerve mitochondria, leading to improvements in sensory function, via heat shock protein induction. The investigators will employ immersion heat treatment to elevate heat shock protein responses that induce positive changes in peripheral nerve mitochondria. One aspect is to confirm the efficacy, safety, and potential for heat treatment to improve sensory dysfunction in human patients with prediabetes. The goal of this proposal is 1) to test the breadth of heat treatment on various forms of neuropathy, 2) identify mechanisms in which heat treatment improves mitochondrial function, and 3) test the efficacy, safety, and potential for heat treatment to improve sensory dysfunction in human patients with prediabetes.
- Conditions
- PreDiabetes, Neuropathy
- Being tested
- Heat Therapy
- Medical subject headings
- Prediabetic State
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Heat TherapyBehavioural
Subjects will undergo 12 hot water immersions of 40.5 degrees Celsius for approximately 45 minutes per session over 4 weeks. Subjects will be immersed up to the shoulder in a 40°C hot tub until rectal temperature (Tre) increases by 1°C (~20 minutes). Subjects will then remain in the water bath submerged to waist level to maintain Tre between 38.5 and 39.0°C for another 30 minutes (approx. total time submerged ~50 minutes). Following hot water immersion, subjects will be monitored for another 10 min, or until Tre falls below 38.5°C. Core temperature will be monitored using either 1) a rectal probe with sterile disposable sheaths or 2) a sterile disposable rectal thermistor probe (401 A/C, Advanced Industrial Systems, Inc., Harrods Creek, KY) to be inserted ~1 inch past the anal sphincter (inserted by participant). Heart rate and blood pressure will be monitored throughout the treatment. Subjects will be continually monitored and removed from the hot bath if Tre exceeds 39.5°C.
| Study group | Role | What they receive |
|---|---|---|
| Heat Therapy Treatment | Experimental | This study will recruit subjects to participate in heat therapy treatment at the University of Kansas Medical Center (KUMC). After pre-screening, informed consent, and enrollment, all subjects will have baseline laboratory assessments as well as an examination for neuropathy and a lower distal leg biopsy (3mm). Subjects will complete 12 heat therapy treatments over the course of 4 weeks. Within 24-48 hours after the last heat therapy experience, post-treatment laboratory assessments as well as an examination for neuropathy and a lower distal leg biopsy (3mm) will be performed. Receives: Behavioral: Heat Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Fasting Blood Glucose (FBG)
The study team will measure fasting blood glucose at baseline and post-intervention.
Measured: At baseline and post-intervention (~4-5 weeks after first visit)
Change in 2-hr Glucose
The study team will measure 2-hr Glucose at baseline and post-intervention. To complete the oral glucose tolerance test (OGTT), the participant will drink a sweet, concentrated solution of glucose (Azer Scientific Glucola, 75 g) within 5 minutes. Afterwards, the participant will wait 2-hrs and blood will be drawn to test glucose and insulin levels.
Measured: At baseline and post-intervention (~4-5 weeks after first visit)
Change in Intraepidermal Nerve Fibers (IENF)
The study team will count intraepidermal nerve fibers at baseline and post-intervention.
Measured: At baseline and post-intervention (~4-5 weeks after first visit)
Secondary outcomes (5)
Change in Quantitative Sensory Testing (QST) Scores
Pressure pain sensitivity is measured by the Multimodal Automated Sensory Testing (MAST) System (measured at the thumbnail). It yields a pressure pain threshold value measured in kg/cm2.
Measured: At baseline and post-intervention (~4-5 weeks after first visit)
Change in Concentration of Heat Shock Protein 72
Serum levels of heat shock proteins (HSP72) will be measured via Western blots and Elisa assays in serum at baseline and post-intervention.
Measured: At baseline and post-intervention (~4-5 weeks after first visit)
Change in Concentration of Heat Shock Protein 25
Serum levels of heat shock proteins (HSP25) will be measured via Western blots and Elisa assays in serum at baseline and post-intervention.
Measured: At baseline and post-intervention (~4-5 weeks after first visit)
Change in Concentration of Heat Shock Protein Transcription Factor 1
Serum levels of heat shock protein transcription factor (HSF1) will be measured via Western blots and Elisa assays in serum at baseline and post-intervention.
Measured: At baseline and post-intervention (~4-5 weeks after first visit)
Utah Early Neuropathy Scale (UENS)
The Utah Early Neuropathy Scale (UENS) is a physical examination scale specific to early sensory predominant polyneuropathy. The UENS emphasizes severity and spatial distribution of pin (sharp) sensation loss in the foot and leg and focuses less on motor weakness. The UENS includes five subscales: motor examination (4), pin sensation (24), allodynia/hyperesthesia (2), large fiber sensation(8) and deep tendon reflexes (4). The UENS total score ranges from 0-42, with a low score indicating a normal neurological exam and a higher score indicating neuropathy.
Measured: At baseline and post-intervention (~4-5 weeks after first visit)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2021
- Study start27 Jul 2020
- Primary completion11 Jul 2022
- Study completion11 Jul 2022
Why it stopped: Difficulties with study recruitment in target population. Subjects who were enrolled completed study activities.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PreDiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This prospective, observational cohort pilot study will recruit 20 patients with prediabetes with or without peripheral neuropathy (painful and non-painful) to participate in a 4-week heat therapy intervention. After screening, informed consent, and enrollment into the study, subjects will undergo a pre-intervention evaluation that will assess metabolic biomarkers and heat shock protein levels (blood), peripheral neuropathy, and epidermal evaluation (skin biopsy). After the skin biopsy has the appropriate time to heal (approximately 7-14 days), the subjects will undergo 45-minute heat treatments in 40°C water, three times weekly, for 4 weeks. After completion of heat treatments, subjects will undergo a repeated post-intervention evaluation and skin biopsy. Statistical approaches will compare pre- and post-heat therapy measures.
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Kansas Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Paige Geiger, PhD, University of Kansas Medical Center
- Investigators
- Paige Geiger, PhD, Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05070741
- Sponsor's protocol ID
- STUDY00143811
- Acronym
- HOTFUN
- Status last verified
- Dec 2024
- First submitted
- 27 Sep 2021
- Last updated
- 24 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Heat Shock Therapy to Improve Mitochondrial Function in Neuropathy
- ClinicalTrials.gov ID
- NCT05070741
- Acronym / sponsor ID
- HOTFUN / STUDY00143811
- Conditions
- PreDiabetes, Neuropathy
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulties with study recruitment in target population. Subjects who were enrolled completed study activities.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of Kansas Medical CenterUniversity, hospital or other
- Study start
- 27 Jul 2020 (actual)
- Primary completion
- 11 Jul 2022 (actual)
- Study completion
- 11 Jul 2022 (actual)
- First posted
- 7 Oct 2021 (actual)
- Results
- Posted 24 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Sensory dysfunction as a result of peripheral nerve damage is a significant problem that leads to reduced quality of life for patients. The prevalence of sensory dysfunction in peripheral neuropathy associates with epidemic increases in prediabetes and diabetes, but also is relevant to chemotherapy treatments and genetic disorders. Clinical approaches to treat peripheral neuropathy and to stimulate axon growth in settings of peripheral axon loss are limited. Although new drugs will hopefully be forthcoming, the most promising approaches likely involve behavioral and lifestyle interventions. Mitochondrial dysfunction is emerging as a key cellular contribution to peripheral axon health and peripheral neuropathy. Mitochondrial deficiencies contribute to neuropathy and include impaired mitochondrial problems with trafficking, mitophagy, fission, and biogenesis. All of these are thought to lead to a bioenergetic crisis, ending in distal axonal degeneration, sensory dysfunction and pain. Heat shock proteins play a critically important role in cellular homeostasis and increasing heat shock protein functions within cells leads to a range of positive improvements, particularly in mitochondria. In addition, new evidence suggests that increasing heat shock protein responses in peripheral nerves has powerful, positive impacts on sensory function and neuropathy.
Our interdisciplinary team will investigate the role of mitochondrial dysfunction in peripheral neuropathy and translate these approaches to improve treatment for patients with peripheral neuropathy. The investigators hypothesize that novel heat treatment interventions that improve mitochondrial function will improve metabolic symptoms and peripheral nerve mitochondria, leading to improvements in sensory function, via heat shock protein induction. The investigators will employ immersion heat treatment to elevate heat shock protein responses that induce positive changes in peripheral nerve mitochondria. One aspect is to confirm the efficacy, safety, and potential for heat treatment to improve sensory dysfunction in human patients with prediabetes. The goal of this proposal is 1) to test the breadth of heat treatment on various forms of neuropathy, 2) identify mechanisms in which heat treatment improves mitochondrial function, and 3) test the efficacy, safety, and potential for heat treatment to improve sensory dysfunction in human patients with prediabetes.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This prospective, observational cohort pilot study will recruit 20 patients with prediabetes with or without peripheral neuropathy (painful and non-painful) to participate in a 4-week heat therapy intervention. After screening, informed consent, and enrollment into the study, subjects will undergo a pre-intervention evaluation that will assess metabolic biomarkers and heat shock protein levels (blood), peripheral neuropathy, and epidermal evaluation (skin biopsy). After the skin biopsy has the appropriate time to heal (approximately 7-14 days), the subjects will undergo 45-minute heat treatments in 40°C water, three times weekly, for 4 weeks. After completion of heat treatments, subjects will undergo a repeated post-intervention evaluation and skin biopsy. Statistical approaches will compare pre- and post-heat therapy measures.
| Arm | Type | Receives |
|---|---|---|
| Heat Therapy Treatment | Experimental | Behavioral: Heat TherapyThis study will recruit subjects to participate in heat therapy treatment at the University of Kansas Medical Center (KUMC). After pre-screening, informed consent, and enrollment, all subjects will have baseline laboratory assessments as well as an examination for neuropathy and a lower distal leg biopsy (3mm). Subjects will complete 12 heat therapy treatments over the course of 4 weeks. Within 24-48 hours after the last heat therapy experience, post-treatment laboratory assessments as well as an examination for neuropathy and a lower distal leg biopsy (3mm) will be performed. |
Who may qualify
- Ages
- 45 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- both males and females,
- ages 45-75,
- have suspected or diagnosed prediabetes with or without neuropathy (to be confirmed at pre-intervention evaluation).
Key exclusion criteria (13 listed)
- skin conditions, circulatory insufficiency, or open wounds in the leg that would interfere with healing from a biopsy;
- stroke or other significant nervous system pathology;
- lidocaine allergy;
- anticipated difficulty with blood clotting due to disorder or use of a blood thinner such as Coumadin, Xarelto, or Eliquis;
- use of any medication used to treat abnormal blood glucose such as Metformin;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Heat TherapySubjects will undergo 12 hot water immersions of 40.5 degrees Celsius for approximately 45 minutes per session over 4 weeks. Subjects will be immersed up to the shoulder in a 40°C hot tub until rectal temperature (Tre) increases by 1°C (~20 minutes). Subjects will then remain in the water bath submerged to waist level to maintain Tre between 38.5 and 39.0°C for another 30 minutes (approx. total time submerged ~50 minutes). Following hot water immersion, subjects will be monitored for another 10 min, or until Tre falls below 38.5°C. Core temperature will be monitored using either 1) a rectal probe with sterile disposable sheaths or 2) a sterile disposable rectal thermistor probe (401 A/C, Advanced Industrial Systems, Inc., Harrods Creek, KY) to be inserted ~1 inch past the anal sphincter (inserted by participant). Heart rate and blood pressure will be monitored throughout the treatment. Subjects will be continually monitored and removed from the hot bath if Tre exceeds 39.5°C. | Behavioural | Heat Therapy Treatment |
Primary outcome
Change in Fasting Blood Glucose (FBG)
Time frame: At baseline and post-intervention (~4-5 weeks after first visit)
The study team will measure fasting blood glucose at baseline and post-intervention.
Change in 2-hr Glucose
Time frame: At baseline and post-intervention (~4-5 weeks after first visit)
The study team will measure 2-hr Glucose at baseline and post-intervention. To complete the oral glucose tolerance test (OGTT), the participant will drink a sweet, concentrated solution of glucose (Azer Scientific Glucola, 75 g) within 5 minutes. Afterwards, the participant will wait 2-hrs and blood will be drawn to test glucose and insulin levels.
Change in Intraepidermal Nerve Fibers (IENF)
Time frame: At baseline and post-intervention (~4-5 weeks after first visit)
The study team will count intraepidermal nerve fibers at baseline and post-intervention.
5 secondary outcomes
Change in Quantitative Sensory Testing (QST) Scores
Time frame: At baseline and post-intervention (~4-5 weeks after first visit)
Change in Concentration of Heat Shock Protein 72
Time frame: At baseline and post-intervention (~4-5 weeks after first visit)
Change in Concentration of Heat Shock Protein 25
Time frame: At baseline and post-intervention (~4-5 weeks after first visit)
Change in Concentration of Heat Shock Protein Transcription Factor 1
Time frame: At baseline and post-intervention (~4-5 weeks after first visit)
Utah Early Neuropathy Scale (UENS)
Time frame: At baseline and post-intervention (~4-5 weeks after first visit)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paige Geiger, PhD principal investigator
University of Kansas Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Heat Therapy in people with PreDiabetes and Neuropathy, run by University of Kansas Medical Center at 1 site in United States.
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 13 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: stopped early, as of the sponsor's last update on 24 Jan 2025. 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 United States. 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?
Yes. Results are posted in the registry (first posted 24 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Fasting Blood Glucose (FBG) (time frame: At baseline and post-intervention (~4-5 weeks after first visit)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Jan 2025.