Evaluation of the Benefit at 6 Months of a 3 Weeks Spa Treatment in the Type 2 Diabetic Patient.

Study Overview
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Brief Summary
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Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia due to deficiency in either insulin secretion, insulin action, or both. There are different types of diabetes. The most common nowadays is type 2 diabetes, characterized by insulin resistance and a relative deficiency of insulin secretion, either of which may dominate to a varying degree. This form of diabetes occurs mainly in mature adults but can also occur at a younger age, or even during adolescence. According to estimates, the number of diabetic subjects in the world increased from 153 million in 1980 to 347 million in 2008. In France, the prevalence of diabetes treated increased from 2.6% to 4.4% between 2000 and 2009, reaching nearly 3 million people. Type 2 diabetes accounts for 92% of cases of diabetes treated, and its share continues to increase due to a relative stability of type 1 diabetes and a steady increase in type 2 diabetes (5.4% per year). The aging of the population, the increase in obesity and the lack of physical activity contribute to the development of type 2 diabetes. According to the Entred study conducted in France between 2001 and 2007, four out of five type 2 diabetic patients were either overweight (39%) or obese (41%). In the long term, unbalanced diabetes exposes to macro-vascular complications such as myocardial infarction and stroke, and microvascular complications affecting the peripheral nervous system, kidneys, retina may result in amputation of the lower limb, renal failure and blindness, respectively. As a result, the risk of death for diabetics is at least twice as high as for non-diabetics. However, a good control of the disease by a lifestyle adaptation (lifestyle and dietary measures, physical activity) with good medical care, and possibly pharmacological, can avoid or significantly reduce the risk of complications. The purpose of dietary and lifestyle measures is to reduce hyperglycaemia and to control the weight of the patient. The implementation of effective dietary measures is a necessary prerequisite for the medication treatment of glycemic control and their application should be continued throughout the course of treatment. The treatment of other cardiovascular risk factors and complications of diabetes is also essential for the management of the diabetic patient. The HAS (Haute Autorité de Santé : High Authority of Health) in its latest recommendations for a drug strategy for glycemic control of type 2 diabetes emphasizes that the short-term goal of decreasing hyperglycemia is the improvement of symptoms (thirst, polyuria, asthenia, weight loss and fuzziness visual) and the prevention of acute complications (infectious and hyperosmolar coma). The longer-term goal is the prevention of chronic microvascular complications (retinopathy, nephropathy and neuropathy), macrovascular (myocardial infarction, stroke, and peripheral arterial occlusive disease) and decreased mortality. The HAS notes, however, that HbA1c as a criterion for substituting morbidity and mortality endpoints in type 2 diabetes is not sufficiently supported in the scientific literature. Be that as it may, HAS recommends individualizing the goal of glycemic control according to the profile of the patient and in particular to mobilize the recommended therapeutic means to reach the HbA1c target, in particular the dietary and hygiene measures. The data in the literature do not allow to define a lower limit for the HbA1c target. For most type 2 diabetic patients, an HbA1c target of less than or equal to 7% is recommended. A target of 6.5% is recommended for newly diagnosed patients with no history of cardiovascular disease and a life expectancy of more than 15 years, as well as for women during pregnancy. An HbA1c target of 8% or less is recommended for patients with proven severe comorbidity and / or limited life expectancy (<5 years), or with advanced or long-lasting macrovascular complications diabetes (> 10 years) and for whom the target of 7% is difficult to achieve because drug intensification causes severe hypoglycaemia, or with a history of macrovascular complication considered as advanced, or with severe chronic renal insufficiency or (stages 4 and 5), as well as for the so-called frail elderly. For elderly people who are sick, the priority is to avoid acute complications due to diabetes (dehydration, hyperosmolar coma) and hypoglycaemia; Pre-meal capillary glucose values of between 1 and 2 g / l and / or an HbA1c level of less than 9% are recommended. There are many molecules available on the pharmaceutical market to treat this disease (biguanides, hypoglycemic sulfonamides, DPP-4 inhibitors, GLP-1 analogues, alpha-glucosidase inhibitors, insulin, etc.). It is important to choose, depending on the clinical profile of the patient, the molecule (s) to be combined in order to achieve the glycated hemoglobin targets set by health organizations.

Detailed Description
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In recent years, many medical decision support software (diagnostic or therapeutic) have emerged to help doctors in their choices. For type 2 diabetes, apart from a decision-making aid tool posted on the HAS website, the Diascope tool can be cited. A group of 12 European experts came together to create this software to help doctors when diabetic patients do not reach their goal. They worked on more than 2000 clinical scenarios and thus established therapeutic recommendations. They prioritized the recommendations in 3 levels. For each patient profile, the most appropriate therapeutic proposals appear in green, inappropriate options appear in red, and acceptable but uncertain options appear in yellow. These two tools can help optimize patient management by finding the therapeutic strategy that is closest to the recommendations that are adapted to each patient. Therapeutic education, which has a key role in the care of these patients, has a demonstrated impact on quality improvement. In this prospective study, the authors also found a link between improved quality of life and lower HbA1c. This study uses the Diabetes Quality of Life (DQOL) score. A more appropriate score allowing a customization of the elements constituting the quality of life is the Audit of Diabetes-Dependent Quality of Life score (ADDQOL score). Physical activity is recommended for multiple reasons in Health. The summary of Inserm's collective expertise perfectly summarizes the benefits and the modalities of a physical activity for Health. There are clear international recommendations on the subject of moderate physical activity of at least 150 minutes per week, for example on the World Health Organization website or in the text of the recommendations of the American College of Sport Medicine and the American Heart Association. Adaptations of these recommendations for older people are also available. Walking and cycling are the two physical activities most cited in these documents because of their progressive and mild characteristics particularly suitable for patients with rheumatological indications and / or significant overweight. However, the practice of cycling can, depending on the natural terrain, involve efforts and pressures in joints and musculotendinous too important. This will often be the case in the natural environment of the most often hilly spas. In addition, there are many practical or psychological obstacles to cycling in a population of patients suffering from chronic pathologies: it's too hard, I do not know how to do it anymore, it's for young people , I am less strong than the others so I can not accompany them in their outings .... The electric assistance bicycle (EVA) can then be useful. A very comprehensive report from the DGS (Direction Générale de la Santé : General Health Direction) of the Canton of Geneva takes stock of the positive impact of the dissemination of routine use of VAE (Available on http://www.impactsante.ch/pdf/EIS_VAE_2006.pdf). Still in Switzerland, J Welker, despite a provocative title, concludes that The electric-assisted bicycle (EVA) is a physical activity in its own right and represents a means to fight sedentariness. These authors suggest from a study conducted in Lausanne that VAE even with a high attendance represents a real physical activity (> 6 MET) on hilly paths. It has been shown on small series with real-time measurements of the effort that the VAE with strong attendance was equivalent to a brisk walk and that the VAE with moderate assistance was intermediate in terms of physical effort between brisk walking and cycling without. It has also been shown that the use of VAE can achieve the objectives recommended for the practice of physical activity. The hydrotherapy has demonstrated its effectiveness especially for indications rheumatology and for the management of obesity (indication metabolic diseases). The benefit of the multifaceted actions implemented during a spa treatment concerns the symptoms, the reduction of pain and / or weight loss. As a result, randomized controlled trials have shown a benefit on quality of life. Metabolic disorders and especially diabetes and overweight are an indication of thermal cures. Two studies have shown positive results of a thermal cure on metabolic disorders. The first is a multicentre study in overweight or obese subjects (8% of whom are diabetic) who has demonstrated a significant benefit on weight and body mass index (BMI) of a spa treatment and the maintenance of this condition. improvement one year later compared to a control group. The second is a monocentric study in which a disappearance of a metabolic syndrome was observed one year after a spa treatment for 50% of patients included and 76% of patients followed at one year. Finally, an improvement in weight, BMI and fasting blood glucose at the end of a spa treatment was found in a preliminary study in 21 subjects with type 2 diabetes, with a decrease of 0.5% in glycated hemoglobin (HbA1c) 3 months after the beginning of the treatment. These positive data on parameters strongly correlated with diabetes (weight, BMI, metabolic syndrome), and on the glycemic parameters of a preliminary study with a small number of diabetic patients justify the completion of a multicenter study to evaluate the benefit to a patient. year of a 3 weeks spa treatment in the type 2 diabetic patient.

Official Title
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Evaluation of the Benefit at 6 Months of a 3 Weeks Spa Treatment in the Type 2 Diabetic Patient. Multicenter Randomized Therapeutic Trial

Conditions
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Diabetes Mellitus, Physical Activity, Dietetic Rules, Therapeutic Education

Intervention / Treatment
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* Other: SPA Treatment with therapeutic education and physical activity
* Other: Week end


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with type 2 diabetes defined by (HAS 2013): a blood glucose level above 1.26 g / l (7.0 mmol / l) after an 8-hour fast and checked twice; or the presence of symptoms of diabetes (polyuria, polydipsia, weight loss) associated with blood glucose (on venous plasma) greater than or equal to 2 g / l (11.1 mmol / l); or blood glucose (on venous plasma) greater than or equal to 2 g / l (11.1 mmol / l) 2 hours after an oral load of 75 g of glucose (criteria proposed by the World Health Organization). Patient with HbA1c at inclusion> 7 and <12% (on an HbA1c dose less than 6 months old at the prescreening) Patient with a BMI ≥ 25 and a weight ≤ 125 kg Patient with appropriate treatment Age ≥ 18 years Available to go on treatment in 6 weeks after inclusion Available for a 12-month follow-up Affiliated to the social security or beneficiary of such a scheme Exclusion Criteria: Diabetes type 1 or secondary Patient with GFR (glomerular filtration rate) <50 ml / min (MDRD formulation) for at least 1 year. Unstable diabetes defined by the knowledge of the questioning of a change in HbA1c of +/- 1 in the last 6 months. With known serious comorbidity and / or limited life expectancy (<5 years), or with advanced macrovascular complications: in particular cardiovascular (acute coronary diseases and / or stroke in the last 6 months) and renal Severe psychiatric pathology or psychosis Pregnant woman, parturient or breastfeeding Contraindication to hydrotherapy Patient with a contraindication to moderate physical activity or cycling (acute coronary artery disease less than 2 years old, musculoskeletal problem of the spine or lower limbs incompatible with cycling). No previous spa treatment for Digestive disorders and metabolic diseases in the current the spa year. Person deprived of liberty or legal protection measure Subject participating to an other clinical study interventional.

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Multicenter, Controlled, Randomized, Open Group Therapeutic Trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 3 weeks SPA Treatment<br>3-week thermal cure: Spa treatment harmonized in the different stations Therapeutic education workshops and conferences common to all stations in the form of practical workshops during supervised lunches Adapted physical activity, workshops are common to all spas and use an electric bike suitable for health (VELIS) with briefing and debriefing. An APA (Adapted Physical Activity) coaching consultation at the end of the cure for personalized post-cure programs and objectives is planned as well as a telephone or internet coaching during the 5 months post-cure (objectives and adaptation, motivation) Maintenance of the usual treatment within 6 months post randomization with optimization of the therapeutic target in HbA1c and therapeutic strategies by the software Diascope and / or HAS Information booklet for inclusion (French Association of Diabetics) | Other: SPA Treatment with therapeutic education and physical activity<br>* 3 weeks SPA Treatment plus therapeutic education plus physical activity<br>|
| Sham Comparator: Discovery week end<br>Maintenance of usual treatment within 6 months post-randomization with optimization of the therapeutic target in HbA1c and therapeutic strategies by Diascope and HAS software In addition, a discovery access to the baths of 2-3 days will be offered to patients. Finally, the information booklet on diabetes will be given at the inclusion (French Federation of Diabetics). | Other: Week end<br>* access to the station for a week end after maintenance of usual treatment during 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c evolution | Difference in mean HbA1c between the intervention group (spa treatment) at 6 months post start of treatment and the reference group (usual care) at 6 months post randomization taking into account (Ancova) the last value of d HbA1c available (at baseline or at baseline). | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Qualitative evolution of HbA1c | Success defined by three criteria for the evolution of HbA1c: percentage of patients with HbA1c less than or equal to 7% (HAS Criterion) or percentage of patients with at least 1% reduction in HbA1c or percentage of patients who achieved the target HbA1c defined at inclusion | 6 months | 
| Quantitative evolution of HbA1c | HbA1C at 12 months in quantitative value adjusted to the value at inclusion | 12 months | 
| Evaluation of the specific quality of life: (ADDQOL) | The ADDQOL (Audit of Diabetes-Dependent Quality of Life Scale) contain 19 domains. These 19 domains ask the respondents to evaluate how their life would be if they did not have diabetes. The scales range from -3 to +1 for 19 life domains (impact rating) and from 0 to +3 in attributed importance (importance rating). A weighted score for each domain is calculated as a multiplier of impact rating and importance rating (ranging from -9 to +3). Lower scores reflect poorer QoL. Finally, a mean weighted impact score (ADDQOL score) is calculated for the entire scale across all applicable domains. | 6 and 12 months | 
| Evaluation of the overall quality of life: (EQ5D- 3L) | Euroquol 5D (EQ5D- 3L) quality of life scale. Euroquol 5D (EQ5D- 3L) quality of life scale. EQ-5D is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life that can be used in a wide range of health conditions and treatments. The EQ5D-3L contains 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). Each dimension has 3 levels (no problem, some problem, extreme problem). | 6 and 12 months | 
| Medical care assessment | evaluation of the medical care of patients (treatments, paramedical procedures, hospitalizations ...), comparison between the 2 groups of treatment modifications. | 6 and 12 months | 
| Biological parameters evolution | Evolution of biological parameters | 6 and 12 months | 
| Overweight evolution BMI | Evolution of overweight (BMI) | 6 and 12 months | 
| Overweight evolution abdominal perimeter | Evolution of overweight (abdominal perimeter) | 6 and 12 months | 
| Clinical repercussions evolution | Evolution at 6 months and 12 months of the clinical repercussions of diabetes (collection of declarative SAEs with validation by a committee). Analysis of hospitalizations related to diabetes (macro and microvascular repercussions, metabolic complications, severe hypoglycaemia). | 6 and 12 months | 
| Physical activity measurement : (GPAQ score) | Measurement of physical activity at 6 and 12 months with Global Physical Activity Questionnaire (GPAQ score).The Global Questionnaire on Physical Exercise (GPAQ), has 16 questions. The score obtained makes it possible to establish three profiles: insufficient level of physical activity, level according to the recommendations, high level | 6 and 12 months | 
| Physical performance measurement | Pre and post cure measurement of physical performance. Evolution of performances during bike rides (VELIS). Profile of the parameters recorded on the VELIS (cardio, speed, electric power supplied by the engine, pressure on the pedals) at the beginning and end of treatment on the same reference course. | During SPA therapy | 
| Self-esteem (Rosenberg score) assessment | Assessment of self-esteem building with the Rosenberg score.The Rosenberg score is between 10 and 40. The interpretation of the results is identical for a man or a woman. score below 25, self-esteem is very low. score between 25 and 31, self-esteem is low. score between 31 and 34, self-esteem is average. score between 34 and 39, self-esteem is strong. score above 39, self-esteem is very strong | 6 and 12 months | 
| Treatment compliance | Evaluate the participation in thermal treatment, education and physical activity | 6 months | 
| Therapeutic objectives evaluation | Evaluation of the achievement of educational objectives of health behaviors by intermediate telephone follow-up. | 3 and 6 months | 
| Side effects evaluation | Evaluation of the side effects of the thermal treatment (SAE reporting). Evaluation of all adverse events attributable to treatment, or not, according to the usual criteria of pharmacovigilance in clinical trials | 6 and 12 months | 
| Subgroup analysis | Sub group analysis on the primary outcome measure (stratification on primo spa therapy and age (median 62 years)). | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HbA1c, Diabetes, Type 2