Heat Therapy in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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Type 2 diabetes mellitus (T2DM) is a significant burden worldwide. In addition to lifestyle intervention, heat therapy has been shown to be effective in improving glycemic control. To date, there are no randomized, controlled trials investigating the efficacy of heat therapy in T2DM. Our aim is to investigate whether heat therapy with natural mineral water can improve blood glucose status in T2DM patients. The HEATED study is a two-arm, randomized, controlled study. Patients with T2DM were randomly assigned to Group A (bath in 38 ° C natural thermal mineral water) or Group B (bath in thermoneutral water - 30-32 ° C). Both groups participate in up to five interventions per week, representing 50 to 60 heat therapies over the 12-week study. Each intervention lasts 30 minutes, preceded by a medical examination.

Detailed Description
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Type 2 diabetes mellitus (T2DM) is a significant burden worldwide. In addition to lifestyle intervention, heat therapy has been shown to be effective in improving glycemic control. To date, there are no randomized, controlled trials investigating the efficacy of heat therapy in T2DM. The study aims to investigate whether heat therapy with natural mineral water can improve blood glucose status in T2DM patients. The HEATED study is a two-arm, randomized, controlled study. Patients with T2DM will be randomly assigned to Group A (bath in 38 ° C natural thermal mineral water) or Group B (bath in thermoneutral water - 30-32 ° C). Both groups will participate in up to five interventions per week, representing 50 to 60 heat therapies over the 12-week study. Each intervention will last 30 minutes, preceded by a medical examination. At baseline, patients' T2DM status will be recorded and possible micro- and macrovascular complications of T2DM are assessed by physical and laboratory tests. In addition, sensory and autonomic neuropathy will be assessed using Neurometer, Neuropad, and 128 Hz tuning fork tests. Quality of life will be assessed using the SF-36 questionnaire. In addition to baseline, patient data will be recorded at 4, 8, and 12 weeks. During routine blood collection, biobank storage will be performed via plus blood samples collection. The primary endpoint will be the change from baseline in glycated hemoglobin by week 12 in both groups. Based on a preliminary estimate of the number of items, 65 patients per group are planned to be included in the HEATED study. The results of the study described above may provide information on the utility of heat therapy in type 2 diabetics. Using the samples stored in the biobank, further analyzes will be performed at the end of the study.

Official Title
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The Effect of HEAT Therapy on patiEnts With Type 2 Diabetes Mellitus (HEATED): Protocol of a Randomized, Two-arm Controlled Trial

Conditions
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Diabetes Mellitus, Type 2, Insulin Resistance

Intervention / Treatment
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* Procedure: Passive heating
* Procedure: Thermoneutral


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patient with type 2 diabetes diagnosed according to the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) guidelines serum glycated hemoglobin (HbA1c) level between 7 and 10% (53-86 mmol/mol) signed written informed consent form Exclusion Criteria: other types of diabetes mellitus patients with poor glycaemic control or unstable diabetes patients with known serious comorbidity and/ or with advanced macrovascular complications active bacterial infection or treatment with antibiotics within 3 weeks open wounds or skin lesions history of skin-related conditions or sensitivity to prolonged water immersion or exposure to pool chemicals severe psychiatric pathology or psychosis pregnancy or breastfeeding judgment by medical provider that heat therapy/ hydrotherapy poses an undue burden or risk participating in other ongoing clinical trials heat or balneotherapy in the past 3 months morbid obesity (body mass index > 40 kg/m2) steroid treatment active autoimmune diseases coronavirus disease 2019 (COVID-19) in the past 3 months

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Passive heating<br>Patients will be randomized to receive whole-body passive heating via 38°C natural thermal mineral water baths. | Procedure: Passive heating<br>* Patients will perform baths in 38°C natural thermal mineral water a maximum of five times per week, over a 12-week period. This will result in a maximum of 60 visits. Each visit will take a maximum of 30 minutes with a physical check-up before and after the bath.<br>|
| Active Comparator: Thermoneutral<br>Patients randomized to the comparator group will dip in thermoneutral natural thermal mineral water (30-32°C). | Procedure: Thermoneutral<br>* Patients will perform baths in 30-32°C natural thermal mineral water a maximum of five times per week, over a 12-week period. This will result in a maximum of 60 visits. Each visit will take a maximum of 30 minutes with a physical check-up before and after the bath.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hemoglobin A1c level | The absolut changes in the hemoglobin A1c from baseline to 12-weeks between the two groups will be compared. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hemoglobin A1c level | Absolute change from baseline to follow-up in hemoglobin A1c level. | 4 and 8 weeks | 
| Change in fasting plasma glucose | Absolute change from baseline to follow-up in fasting plasma glucose. | 4,8, and 12-weeks | 
| Change in fasting insulin | Absolute change from baseline to follow-up in fasting insulin. | 4,8, and 12-weeks | 
| Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) | Absolute change from baseline to follow-up in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). | 4,8, and 12-weeks | 
| Decrease of daily insulin dose | Absolute change from baseline to follow-up of the daily insulin dose. | 4,8, and 12-weeks | 
| Change in body mass index | Absolute change from baseline to follow-up in body mass index. Weight and height will be combined to report BMI in kg/m^2. | 4,8, and 12-weeks | 
| Change in mean blood pressure | Absolute change from baseline to follow-up in mean blood pressure. | 4,8, and 12-weeks | 
| Change in heart output | Absolute change from baseline to follow-up in heart output. | 4,8, and 12-weeks | 
| Change in the prevalence of electrocardiogram events | Change in the prevalence of electrocardiogram events from baseline to follow-up. Electrocardiogram events represent a composite endpoint of any new events detected using a 12 lead electrocardiogram (e.g., myocardial infarction, atrial fibrillation, atrioventricular block, etc.). | 4,8, and 12-weeks | 
| Change in the proportion of hypertension | Absolute change from baseline to follow-up in the proportion of hypertension | 4,8, and 12-weeks | 
| Change in the proportion of retinopathy | Absolute change from baseline to follow-up in the proportion of retinopathy | 4,8, and 12-weeks | 
| Change in the proportion of nephropathy | Absolute change from baseline to follow-up in the proportion of nephropathy | 4,8, and 12-weeks | 
| Change in the proportion of neuropathy | Absolute change from baseline to follow-up in the proportion of neuropathy | 4,8, and 12-weeks | 
| Change in total cholesterol level | Absolute change from baseline to follow-up in total cholesterol level. | 4,8, and 12-weeks | 
| Change in low-density lipoprotein cholesterol level | Absolute change from baseline to follow-up in low-density lipoprotein cholesterol level. | 4,8, and 12-weeks | 
| Change in high-density lipoprotein cholesterol level | Absolute change from baseline to follow-up in high-density lipoprotein cholesterol level. | 4,8, and 12-weeks | 
| Change in triglyceride level | Absolute change from baseline to follow-up in triglyceride level. | 4,8, and 12-weeks | 
| Change in alkaline phosphatase (ALP) | Absolute change from baseline to follow-up in alkaline phosphatase (ALP). | 4,8, and 12-weeks | 
| Change in alanine transaminase (ALT) | Absolute change from baseline to follow-up in alanine transaminase (ALT). | 4,8, and 12-weeks | 
| Change in aspartate transaminase (AST) | Absolute change from baseline to follow-up in aspartate transaminase (AST). | 4,8, and 12-weeks | 
| Change in gamma-glutamyl transferase (GGT). | Absolute change from baseline to follow-up in gamma-glutamyl transferase (GGT). | 4,8, and 12-weeks | 
| Change in glomerular filtration rate | Absolute change from baseline to follow-up in glomerular filtration rate. | 4,8, and 12-weeks | 
| Change in creatinine level | Absolute change from baseline to follow-up in creatinine. | 4,8, and 12-weeks | 
| Change in thrombocyte aggregation | Absolute change from baseline to follow-up in thrombocyte aggregation. | 4,8, and 12-weeks | 
| Heat Shock Protein expression | Difference between the two groups in the level of protein expression using flow cytometry. | 4,8, and 12-weeks | 
| Insulin signaling in polymorphonuclear cells | Difference between the two groups in the level of protein expression using flow cytometry. | 4,8, and 12-weeks | 
| Lipidom of polymorphonuclear cells | High sensitivity shotgun mass spectrometry will be used to characterize the lipidome of plasma, and polymorphonuclear blood cells. | 4,8, and 12-weeks | 
| Lipidom of plasma cells | High sensitivity shotgun mass spectrometry will be used to characterize the lipidome of plasma, and polymorphonuclear blood cells. | 4,8, and 12-weeks | 
| Change in obstructive sleep apnea proportion | Change in the proportion of obstructive sleep apnea from baseline to follow-up | 4,8, and 12-weeks | 
| Change in the proportion of abnormal overnight pulse oximetry | Absolute change from baseline to follow-up in the proportion of abnormal overnight pulse oximetry. | 4,8, and 12-weeks | 
| Change in 24-hour blood pressure | Absolute change from baseline to follow-up in 24-hour blood pressure | 4,8, and 12-weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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insulin resistance, balneotherapy, additional therapy, alternative therapy, heat shock proteins