Immunosuppression and Diet: the Role of Inflammation in the Adipose Tissue Remodeling

Study Overview
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Brief Summary
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The main goal of this project is to evaluate the effect of immunosuppression in the weight loss and in the metabolic status of patients after liver transplantation. It is also the purpose of this project to investigate why patients become overweight and obese after liver transplantation.

Detailed Description
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Overweight and obese post-liver transplantation patients will receive a diet to promote weight loss during 6 months. The control group (overweight and obese subjects) will be submitted to the same protocol: The participants will be interviewed at baseline and after 30, 60, 90 and 180 days from baseline. The following measures will be assessed: body composition (fat body% and free fat body%), anthropometric measures (height, weight, body mass index, waist circumference and abdominal circumference), blood pressure, basal metabolic rate, behavioral symptoms and peripheral biomarkers in the serum. Behavioral symptoms will be assessed using the following self-reported questionnaires: Beck Depression Inventory (depression symptoms), Beck Anxiety Inventory (anxiety symptoms), Medical Outcomes Study 36 - Item Short - Form Health Survey (quality of life) and Perceived Stress Scale (stress). Enrolled participants will receive a restrictive diet calculated based on individual requirements aiming the loss of around 5%-10% of weight/ 6 months of intervention.

Official Title
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Immunosuppression and Diet: the Role of Inflammation in the Adipose Tissue Remodeling After Liver Transplantation

Conditions
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Obesity, Liver Transplantation

Intervention / Treatment
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* Other: Weight loss diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CONTROL GROUP: Women/men aged 18-60 years old; Body mass index 25-40 kg/m2. IMMUNOSSUPPRESSED PATIENTS: Women/men aged 18-60 years old; Body mass index 25-40 kg/m2; liver transplantation between 1-3 years from the time of recruitment. Exclusion Criteria: CONTROL GROUP: Pregnant or lactating womenbuse of alcohol or drugs Endocrine disease Use of hormones which interferes in the weight Use of insulin or anti-inflammatory, and antidepressants drugs Use of drugs to loss weight Immunosuppressed patients Subjects in another weight loss program Subjects submitted to bariatric surgery IMMUNOSSUPPRESSED PATIENTS: Pregnant or lactating women Abuse of alcohol or drugs Endocrine disease Use of hormones which interferes in the weight Use of insulin or antidepressants drugs Use of drugs to loss weight Subjects in another weight loss program Subjects submitted to bariatric surgery, re-transplanted patients, hepatic insufficiency.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Control<br>The volunteers (overweight and obese) will receive nutritional counseling and a weight loss diet. | Other: Weight loss diet<br>* Weight loss diet composed of 30% lipids, 30% proteins and 40% carbohydrates.<br>|
| Experimental: Immunosuppressed patients<br>The volunteers (liver transplantation) will receive nutritional counseling and a weight loss diet. | Other: Weight loss diet<br>* Weight loss diet composed of 30% lipids, 30% proteins and 40% carbohydrates.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in weight measurement from baseline until 6 months follow up. | The weight loss will be measured by weighing volunteers | Baseline and 30, 60, 90 and 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body composition from baseline until 6 months follow up. | The effect of the weight loss diet in body composition will be measured by bioimpedance. | Baseline and 30, 60, 90 and 180 days | 
| Change in basal metabolic rate from baseline until 6 months follow up. | Basal metabolic rate will be measured by calorimetry. | Baseline and 30, 60, 90 and 180 days | 
| Change in inflammatory mediators serum levels from baseline until 6 months follow up. | Nutritional effect in the levels of interleukins, such as Interleukin-1, interleukin-6 and interleukin-10, interleukin-17, tumor necrosis factor and protein C reactive. | Baseline and 30, 60, 90 and 180 days | 
| Change in depressive symptoms from baseline until 6 months follow up. | Nutritional effect in depressive symptoms will be measured by the Beck Depression Inventory. | Baseline and 30, 60, 90 and 180 days | 
| Change in anxiety symptoms from baseline until 6 months follow up. | Nutritional effect in anxiety symptoms will be measured by the Beck Anxiety Inventory. | Baseline and 30, 60, 90 and 180 days | 
| Change in quality of life from baseline until 6 months follow up. | Nutritional effect in quality of life will be measured by Medical Outcomes Study 36 - Item Short - Form Health Survey. | Baseline and 30, 60, 90 and 180 days | 
| Change in perceived stress from baseline until 6 months follow up. | Nutritional effect in perceived stress will be measured by the Perceived Stress Scale. | Baseline and 30, 60, 90 and 180 days | 
| Change in quality of diet from baseline until 6 months follow up. | Nutritional effect in quality of diet will be measured by the Healthy Eating Index-10. | Baseline and 30, 60, 90 and 180 days | 
| Changes in serum levels of neurotrophic factors from baseline until 6 months follow up. | Nutritional effect in the serum levels of brain-derived neurotrophic factor, glial-derived neurotrophic factor and neurotrophin-3 and neurotrophin 4/5. | Baseline and 30, 60, 90 and 180 days | 
| Change in metabolic markers serum levels from baseline until 6 months follow up. | Nutritional effect in the levels of triglycerides, cholesterol and glucose | Baseline and 30, 60, 90 and 180 days | 
| Characterization of the immunological response of liver transplanted patients from baseline until 6 months follow up. | Analysis of cytokines in the sera of immunosupressed patients. | Baseline and 30, 60, 90 and 180 days | 
| Characterization of the immunological response of liver transplanted patients from baseline until 6 months follow up.. | Analysis of cytokines in cell culture (PBMC) of immunosupressed patients. | Baseline and 30, 60, 90 and 180 days | 
| Characterization of the immunological profile of liver transplanted patients in the baseline. | The cells will be immuno-phenotyped for the ex vivo condition and also submitted to culture in the presence of different stimuli. | Baseline. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Liver transplantation, weight loss diet, immunosuppression