Heat Therapy in Patients With Type 2 Diabetes Mellitus

Diabetes Mellitus, Type 2 Clinical Trial

— HEATED  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05237219
• Other study ID #: 818-2/2022/EÜIG
• Status: Withdrawn
• Phase: N/A
• Start date: May 1, 2022
• Est. completion date: June 1, 2024

Study information

• Verified date: April 2023
• Source: University of Pecs
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 1, 2024
• Est. primary completion date: January 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Insulin Resistance

Intervention

Procedure:
• Passive heating
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.
• Thermoneutral
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.

Locations

Country	Name	City	State
Hungary	Institute for Translational Medicine, University of Pécs	Pécs

Sponsors (1)

Lead Sponsor	Collaborator
University of Pecs

Country where clinical trial is conducted

Hungary, 

References & Publications (7)

Brunt VE, Howard MJ, Francisco MA, Ely BR, Minson CT. Passive heat therapy improves endothelial function, arterial stiffness and blood pressure in sedentary humans. J Physiol. 2016 Sep 15;594(18):5329-42. doi: 10.1113/JP272453. Epub 2016 Jun 30. — View Citation

Hoekstra SP, Bishop NC, Faulkner SH, Bailey SJ, Leicht CA. Acute and chronic effects of hot water immersion on inflammation and metabolism in sedentary, overweight adults. J Appl Physiol (1985). 2018 Dec 1;125(6):2008-2018. doi: 10.1152/japplphysiol.00407.2018. Epub 2018 Oct 18. — View Citation

Hooper PL, Balogh G, Rivas E, Kavanagh K, Vigh L. The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes. Cell Stress Chaperones. 2014 Jul;19(4):447-64. doi: 10.1007/s12192-014-0493-8. Epub 2014 Feb 13. — View Citation

Hooper PL. Hot-tub therapy for type 2 diabetes mellitus. N Engl J Med. 1999 Sep 16;341(12):924-5. doi: 10.1056/NEJM199909163411216. No abstract available. — View Citation

Romeo GR, Lee J, Shoelson SE. Metabolic syndrome, insulin resistance, and roles of inflammation--mechanisms and therapeutic targets. Arterioscler Thromb Vasc Biol. 2012 Aug;32(8):1771-6. doi: 10.1161/ATVBAHA.111.241869. — View Citation

Salas-Salvado J, Diaz-Lopez A, Ruiz-Canela M, Basora J, Fito M, Corella D, Serra-Majem L, Warnberg J, Romaguera D, Estruch R, Vidal J, Martinez JA, Aros F, Vazquez C, Ros E, Vioque J, Lopez-Miranda J, Bueno-Cavanillas A, Tur JA, Tinahones FJ, Martin V, Lapetra J, Pinto X, Daimiel L, Delgado-Rodriguez M, Matia P, Gomez-Gracia E, Diez-Espino J, Babio N, Castaner O, Sorli JV, Fiol M, Zulet MA, Bullo M, Goday A, Martinez-Gonzalez MA; PREDIMED-Plus investigators. Effect of a Lifestyle Intervention Program With Energy-Restricted Mediterranean Diet and Exercise on Weight Loss and Cardiovascular Risk Factors: One-Year Results of the PREDIMED-Plus Trial. Diabetes Care. 2019 May;42(5):777-788. doi: 10.2337/dc18-0836. Epub 2018 Nov 2. — View Citation

Sebok J, Edel Z, Vancsa S, Farkas N, Kiss S, Eross B, Torok Z, Balogh G, Balogi Z, Nagy R, Hooper PL, Geiger PC, Wittmann I, Vigh L, Dembrovszky F, Hegyi P. Heat therapy shows benefit in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Int J Hyperthermia. 2021;38(1):1650-1659. doi: 10.1080/02656736.2021.2003445. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in hemoglobin A1c level	Absolute change from baseline to follow-up in hemoglobin A1c level.	4 and 8 weeks
Secondary	Change in fasting plasma glucose	Absolute change from baseline to follow-up in fasting plasma glucose.	4,8, and 12-weeks
Secondary	Change in fasting insulin	Absolute change from baseline to follow-up in fasting insulin.	4,8, and 12-weeks
Secondary	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
Secondary	Decrease of daily insulin dose	Absolute change from baseline to follow-up of the daily insulin dose.	4,8, and 12-weeks
Secondary	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
Secondary	Change in mean blood pressure	Absolute change from baseline to follow-up in mean blood pressure.	4,8, and 12-weeks
Secondary	Change in heart output	Absolute change from baseline to follow-up in heart output.	4,8, and 12-weeks
Secondary	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
Secondary	Change in the proportion of hypertension	Absolute change from baseline to follow-up in the proportion of hypertension	4,8, and 12-weeks
Secondary	Change in the proportion of retinopathy	Absolute change from baseline to follow-up in the proportion of retinopathy	4,8, and 12-weeks
Secondary	Change in the proportion of nephropathy	Absolute change from baseline to follow-up in the proportion of nephropathy	4,8, and 12-weeks
Secondary	Change in the proportion of neuropathy	Absolute change from baseline to follow-up in the proportion of neuropathy	4,8, and 12-weeks
Secondary	Change in total cholesterol level	Absolute change from baseline to follow-up in total cholesterol level.	4,8, and 12-weeks
Secondary	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
Secondary	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
Secondary	Change in triglyceride level	Absolute change from baseline to follow-up in triglyceride level.	4,8, and 12-weeks
Secondary	Change in alkaline phosphatase (ALP)	Absolute change from baseline to follow-up in alkaline phosphatase (ALP).	4,8, and 12-weeks
Secondary	Change in alanine transaminase (ALT)	Absolute change from baseline to follow-up in alanine transaminase (ALT).	4,8, and 12-weeks
Secondary	Change in aspartate transaminase (AST)	Absolute change from baseline to follow-up in aspartate transaminase (AST).	4,8, and 12-weeks
Secondary	Change in gamma-glutamyl transferase (GGT).	Absolute change from baseline to follow-up in gamma-glutamyl transferase (GGT).	4,8, and 12-weeks
Secondary	Change in glomerular filtration rate	Absolute change from baseline to follow-up in glomerular filtration rate.	4,8, and 12-weeks
Secondary	Change in creatinine level	Absolute change from baseline to follow-up in creatinine.	4,8, and 12-weeks
Secondary	Change in thrombocyte aggregation	Absolute change from baseline to follow-up in thrombocyte aggregation.	4,8, and 12-weeks
Secondary	Heat Shock Protein expression	Difference between the two groups in the level of protein expression using flow cytometry.	4,8, and 12-weeks
Secondary	Insulin signaling in polymorphonuclear cells	Difference between the two groups in the level of protein expression using flow cytometry.	4,8, and 12-weeks
Secondary	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
Secondary	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
Secondary	Change in obstructive sleep apnea proportion	Change in the proportion of obstructive sleep apnea from baseline to follow-up	4,8, and 12-weeks
Secondary	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
Secondary	Change in 24-hour blood pressure	Absolute change from baseline to follow-up in 24-hour blood pressure	4,8, and 12-weeks

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