The Effect of Hypocaloric Diet Associated With tDCS on Weight Loss and Metabolic Profile

Study Overview
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Brief Summary
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To compare four weeks of transcranial direct current stimulation (tDCS) versus placebo associated with a reduced caloric diet on weight loss, glycemic control and regulators of hunger and satiety in overweight or obese subjects with different degrees of glucose tolerance, submitted to hypocaloric diet.

Detailed Description
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In order to assess whether tDCS treatment associated with a reduced caloric diet can improve weight loss, overweight or obese subjects will be recruited by advertisement on the web page of Porto Alegre Clinical Hospital, local newspaper and television, or referred by a doctor or nutritionist, from external to HCPA services. After screening and selection, patients will undergo a clinical, laboratory and nutritional evaluation. There will be a standard assessment protocol that includes: a complete clinical evaluation and socioeconomic status, assessment of physical activity, questionnaires of quality of life, sleep, depression and anxiety and body composition assessment. In the laboratory evaluation the biochemistry exams include an oral glucose tolerance test (OGGT 75g), a meal tolerance test (MTT), serum glucose, Cholesterol, HDL-cholesterol, triglycerides, glycated hemoglobin and glycated albumin. The resting metabolic rate will be determine by indirect calorimetry. Besides, a 100-mm visual-analog scales will be used to measure a self-reported ratings of appetite, hunger, satiety and food craving. Patients will also be prescribed a low caloric diet and individual counseling from a dietician in order to reduce 3% of their initial weight over 4-week treatment. Moreover, they will do one tDCS session a day (active or sham stimulation as previous randomization) for 5 consecutive days, during these four weeks of treatment (20 sessions). Transcranial direct current stimulation (tDCS) is a non-invasive method of brain stimulation in which a small current is applied to the scalp. This technique uses a weak safety current of 2 milliampere (mA) for 20 minutes which may increase (anodal tDCS) or decrease (cathodal tDCS) cortical excitability. During all of tDCS sessions, a film with images of food that usually elicit craving will be presented and after the end of each session, visual analog scales will be applied to assess hunger, satiety and presence of food craving. Finally, attention and mood scales will be applied periodically in addition to a questionnaire of adverse effects and use of tDCS. At the end of the 4-week diet and tDCS, all patients will be submitted to the same clinical, laboratory, nutrition and feeding behavior exams applied at baseline. Finally, participants should come in 3 and 6 months after the end of the protocol for reassessment weight, body composition by bioelectrical impedance and answer questionnaires. An interim analysis will be performed when 12 patients will be included.

Official Title
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The Effect of Hypocaloric Diet Associated With tDCS on Weight Loss and Metabolic Profile: a Pilot, Double Blind, Randomized, Placebo-controlled Study

Conditions
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Prediabetes, Obesity, Weight Loss, Diabetes, Overweight

Intervention / Treatment
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* Device: Active tDCS
* Behavioral: Hypocaloric diet
* Device: Sham tDCS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women of childbearing potential who are using medically approved birth control methods (eg hormonal contraceptives, intra uterine device (IUDs), barrier contraception) and who agree to use the same methods of contraception throughout the course of the study. BMI 25 ≥ 35 Kg/m2 at screening Stable weight for at least 12 weeks prior to screening Able and willing to provide written informed consent and to comply with the requirements of the study protocol Exclusion Criteria: Pregnant or intend to become pregnant during the study period or who are currently breastfeeding. Women in perimenopause / menopause, or postmenopausal status, or who have had early menopause (under 40 years) or have had a hysterectomy or oophorectomy. Diagnosis or history of diabetes Mellitus type 1, diabetes resulting from pancreatic injury or secondary forms of diabetes, such as, for example, Cushing's syndrome and acromegaly. 3.1. Metabolic and acute complications of diabetes such as ketoacidosis and hyperosmolar coma within the past six months. Gastrointestinal disease clinically symptomatic including, among others, inflammatory bowel disease and/or malabsorption diseases. Have received nutritional counseling in the last six months by a nutritionist. History of severe depression or other serious psychiatric comorbidities. History of gastric bypass, antrectomy or small bowel resection. History of chronic pancreatitis or idiopathic acute pancreatitis Myocardial infarction (MI), coronary arteries bypass surgery, post-transplant cardiomyopathy or stroke in the last 6 months Any abnormality in clinical laboratory tests which might prevent safe participation in the study Diagnosed and / or treated tumor (except basal cell skin cancer, carcinoma in situ of the cervix or prostate cancer in situ) in the last five years. History of known hemoglobinopathy and chronic anemia. Donation of one unit (500 ml) of blood or more, significant blood loss equivalent to at least one unit of blood within the last 2 weeks or blood transfusion in the past 8 weeks. Treatment with any oral antidiabetic drugs and / or herbal preparations or medications that do not require a prescription and can affect glycemic control within 12 weeks prior to screening. Chronic treatment with oral or parenteral corticosteroids (> 7 consecutive days of treatment) within 4 weeks prior to screening. Treatment with weight loss agents (e.g., orlistat, sibutramine, topiramate, bupropion) in the last 12 weeks prior to screening. Treatment with mineral oil or fiber supplementation (e.g., Benefiber, Metamucil, among others). Treatment with lipid-lowering drugs which have not been kept on a stable dose for the past 8 weeks before screening. Treatment with thyroid replacement hormones which has not been kept on a stable dose for the past 12 weeks prior to screening. Use of drugs under investigation within 30 days or 5 half-lives (whichever is longer) before screening unless the guidelines of local health authorities require a longer period. Any of the following laboratory abnormalities identified in the screening by history and / or tests brought by the patient or that are part of this protocol, as described in section 4.3.4.6 of this project: 21.1. Alanine aminotransferase (ALT) and / or Aspartate aminotransferase (AST) > 3 times the upper limit of normal 21.2. Glomerular filtration rate estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation ≤ 30 ml per min per 1,73 m2 21.3. Thyroid stimulating hormone (TSH) outside the normal range 21.4. Fasting triglycerides ≥ 400 mg / dL. 21.5. History of active substance abuse (including alcohol) within the past year Any condition or concomitant medical disorder, not provided for in other items which in the opinion of the investigator, probably: 22.1. Interfere with the patient's ability to complete the entire study period or participate in all activities of the study 22.2. Require during the study, administration of a treatment that may affect the interpretation of efficacy and safety data Patients potentially unreliable and those considered by the investigator as unsuitable for the study

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active tDCS + Diet<br>The participants will receive active tDCS treatment every day for 5 days per week, a total of 20 sessions. They will also be prescribed a hypocaloric dietary during these 4-week treatment. | Device: Active tDCS<br>* The anode electrode will be placed over F4 position and the cathode electrode over F3, right and left respectively (using EEG 10/20 system). The electric current will be ramped up until it reaches 2 milliampere (mA), and subjects will be stimulated for 20 min.<br>* Other names: Active;Behavioral: Hypocaloric diet<br>* A hypocaloric dietary prescription and individual counseling from a dietician in order to reduce 3% of their initial weight over 4-week treatment.<br>* Other names: Diet;|
| Sham Comparator: Sham tDCS + Diet<br>The participants will receive sham tDCS treatment every day for 5 days per week, a total of 20 sessions. They will also be prescribed a hypocaloric dietary during these 4-week treatment. | Behavioral: Hypocaloric diet<br>* A hypocaloric dietary prescription and individual counseling from a dietician in order to reduce 3% of their initial weight over 4-week treatment.<br>* Other names: Diet;Device: Sham tDCS<br>* The electrodes will be placed at the same positions as in active stimulation; however, the device will be turned off after 30 s of stimulation.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight loss | 3% weight loss | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in hormone levels after 4 week treatment | Changes in hormone levels of satiety, appetite and endocrine pancreas, such as insulin comparing baseline to end of intervention. | baseline and 4 weeks | 
| Glycated Albumin | Reduction in fasting glycated albumin compared to baseline | baseline and 4 weeks | 
| Fasting Plasma Glucose | Reduction in fasting plasma glucose from baseline | baseline and 4 weeks | 
| Homeostatic Model Assessment (HOMA) | Insulin sensitivity index (HOMA-S) and Beta-cell dysfunction (HOMA-beta) | 4 weeks | 
| Body Mass Index (BMI) | Number of patients who achieved a BMI reduction unit | 4 weeks | 
| Intake of calories | Reduction or maintenance of the prescribed intake of calories during the 4-week intervention, in kcal/day, using a 3 days of food record, with food weighing. | 4 weeks | 
| Weight, waist circumference and total body fat loss after 3 and 6 month of end of intervention | weight and waist circumference loss | 3 and 6 month after end of intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prediabetes, tDCS, transcranial direct current stimulation, obesity, diabetes