Phlebotomy and Lifestyle and Diet Advices vs Lifestyle and Diet Advices Only in Patients With Dysmetabolic Liversiderosis

Study Overview
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Brief Summary
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Insulin resistance-associated hepatic iron overload (IR-HIO), also defined as dysmetabolic iron overload syndrome or dysmetabolic liversiderosis, is a common cause or iron overload in France, mainly in middle-age patients with increased serum ferritin levels associated with normal serum transferrin saturation, and normal serum iron concentration in the absence of other known cause of increased serum ferritin levels. Treatment includes a combination of dietary measures and physical activity to correct metabolic disorders. Phlebotomies seem to be beneficial when serum ferritin level is high. This study aims at comparing the effect of iron depletion (by phlebotomy) plus lifestyle and diet advices versus lifestyle and diet advices alone on blood glucose level and insulin sensitivity in subjects with IR-HIO in order to assess the benefits of phlebotomies on the reduction of risk of diabetes and cardiovascular associated complications.

Detailed Description
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Non applicable

Official Title
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Prospective Randomized Study Comparing the Effect of Phlebotomy and Lifestyle and Diet Advices vs Lifestyle and Diet Advices Only on Glycemia in Patients With Dysmetabolic Liversiderosis

Conditions
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Liver Cirrhosis, Iron Overload

Intervention / Treatment
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* Procedure: Phlebotomy
* Behavioral: Lifestyle and diet advices


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age over 18 Signed written informed consent Ferritin ≥ 450 µg/L and ≤ 1500 µg/L Hepatic iron overload proved by MRI or histological biochemical measurement (Iron hepatic concentration ≥ 50 μmol/g) At least one of the following criteria : Body mass index > 25 kg/m² Systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90 mmHg or antihypertensive treatment Abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women) Fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment Fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment Fasting blood glycemia ≥ 5.6 mmol/L Exclusion Criteria: Subjects deprived of their liberty by judicial or administrative decision Pregnant women Other causes of increased serum ferritin levels: Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases Hyper-hemolysis Alcohol consumption more than 210 g for men and 140 g for women per week within the year before inclusion Haemochromatosis established by the C282Y homozygous genotype Chronic hepatic cytolysis due to : viral infection (HBV, HCV), alcohol, hyperthyroid disease, celiac disease, drug or immune hepatitis Increased serum ferritin levels - cataract syndrome (familial cataract or personal history of cataract before 50 years of age) Low ceruloplasmin level Porphyria (cutaneous signs) Contraindication of phlebotomy Haemoglobin <13 g/dL for men and <12g/dL for women (threshold established by the French Blood Agency) Congestive heart failure or coronary heart disease Hepatic failure (TP<60%), renal failure (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) Poor venous system Fasting blood glycemia > 7 mmol/L or type 1 or type 2 diabetes, treated or not Use of drugs known to have anti-steatotic effects : metformin, thiazolidinedione

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phlebotomy + lifestyle and diet advices<br> | Procedure: Phlebotomy<br>* From 300 to 400mL for women; From 350 to 450mL for men<br>* Other names: Non applicable;|
| Active Comparator: Lifestyle and diet advices<br> | Behavioral: Lifestyle and diet advices<br>* 2 Booklets with Dietary and physical activity advices<br>* Other names: Non applicable;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting blood glycemia (T0 of Oral Glucose Tolerance Test) |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Body mass index > 25 kg/m² |  | 12 months | 
| Rate of systolic blood pressure ≥ 130mmHg or diastolic blood pressure ≥ 85 mmHg or antihypertensive treatment |  | 12 months | 
| Rate of abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women) |  | 12 months | 
| Rate of fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment |  | 12 months | 
| Rate of fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment |  | 12 months | 
| Rate of fasting glycemia ≥ 5.6 mmol/L |  | 12 months | 
| HbA1c value |  | 12 months | 
| Quality of life estimated with SF36 form and tolerance to treatment |  | 12 months | 
| Insulinoresistance indexes calculated at T0 and T30 min of Oral Glucose Tolerance Test (OGTT) |  | 12 months | 
| Biological markers: CRP, hyaluronic acid, fibrometer |  | 12 months | 
| myocardial deformation | Two dimensional (2D) speckle tracking echocardiography (STE) | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phlebotomy, Dysmetabolic liversiderosis, Hepatic Iron overload