Heat Shock Therapy to Improve Mitochondrial Function in Neuropathy

Not Applicable

Terminated

Conditions: Neuropathy
PreDiabetes

Interventions: Behavioral: Heat Therapy

Registration Number: NCT05070741

Lead Sponsor: University of Kansas Medical Center

Brief 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 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 3

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Heat Therapy Treatment	Heat Therapy	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.

Primary Outcome Measures

Name	Time	Method
Change in Fasting Blood Glucose (FBG)	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	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)	At baseline and post-intervention (~4-5 weeks after first visit)	The study team will count intraepidermal nerve fibers at baseline and post-intervention.

Secondary Outcome Measures

Name	Time	Method
Change in Concentration of Heat Shock Protein 72	At baseline and post-intervention (~4-5 weeks after first visit)	Serum levels of heat shock proteins (HSP72) will be measured via Western blots and Elisa assays in serum at baseline and post-intervention.
Change in Quantitative Sensory Testing (QST) Scores	At baseline and post-intervention (~4-5 weeks after first visit)	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.
Change in Concentration of Heat Shock Protein 25	At baseline and post-intervention (~4-5 weeks after first visit)	Serum levels of heat shock proteins (HSP25) will be measured via Western blots and Elisa assays in serum at baseline and post-intervention.
Change in Concentration of Heat Shock Protein Transcription Factor 1	At baseline and post-intervention (~4-5 weeks after first visit)	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.
Utah Early Neuropathy Scale (UENS)	At baseline and post-intervention (~4-5 weeks after first visit)	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.