Effects of Phlebotomy on Insulin Sensitivity in Insulin Resistance-associated Hepatic Iron Overload Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate efficacy of phlebotomy on insulin sensitivity as evaluated by euglycemic-hyperinsulinic clamp in insulin resistance-associated hepatic iron overload patients.

Detailed Description
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The main objective of this study is to evaluate in patients with HSD effects of treatment with phlebotomy rules with lifestyle and dietary rules versus lifestyle modifications alone on peripheral insulin resistance (assessed by hyperinsulinemic clamp). Secondary objectives are: to study in all patients with HSD the relationship between the amount of iron intrahepatic and degree of peripheral insulin resistance and liver before therapeutic intervention. to study and compare the effects of phlebotomy treatment versus no treatment on: Plasma levels of adipocytokines, Plasma concentrations of inflammatory markers and markers of insulin resistance, The serum ferritin, The post-hepatic clearance of insulin, The surface of the abdominal visceral fat and subcutaneous abdominal.

Official Title
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Effects of Phlebotomy on Insulin Sensitivity in Insulin Resistance-associated Hepatic Iron Overload Patients

Conditions
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Insulin Resistance, Iron Overload

Intervention / Treatment
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* Procedure: phlebotomy
* Behavioral: dietary and lifestyle counseling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 70 years Ferritin between 450 and 1000 µg/L Hepatic iron overload proved by MRI (CHF >36 µmol/g) Body mass index > 25 kg/m² Fasting glycemia <1,26 g/L HbA1c < 6,5% Signed written and informed consent Exclusion Criteria: Other causes of hyperferritinemia: Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases Hyperferritinemia-cataract syndrome (familial cataract or personal history of cataract before 50 years old) Low ceruloplasmin level Porphyria (cutaneous signs) Haemochromatosis established by the genotype (C282Y homozygous or C282Y/H63D coumpound heterozygous genotypes) Contraindication of phlebotomy Haemoglobin <13,5 g/dL (threshold established by the Etablissement Français du Sang) Heart failure or coronary heart diseases Hepatic failure, renal (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) Poor venous system Viral, immune, genetic, vascular, malignant or toxic chronic hepatic disease Alcohol consumption more than 21 doses per week during 5 years or more Type 1 or type 2 diabetes Oral anti-diabetic, corticoids or immune suppressor drugs Hepatic severe disease Claustrophobia, having a pace-maker or intracerebral clips Subjects deprived of their liberty by judicial or administrative decision, subjects that are not affiliated to social security or topics exclusion period of a previous study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phlebotomy<br>phlebotomy associated with dietary and lifestyle counseling | Procedure: phlebotomy<br>* 7 ml/kg without exceeding 500 mL<br>* Other names: Non applicable.;Behavioral: dietary and lifestyle counseling<br>* dietary and lifestyle counseling<br>* Other names: Non applicable.;|
| Active Comparator: Lifestyle counseling<br>dietary and lifestyle counseling | Behavioral: dietary and lifestyle counseling<br>* dietary and lifestyle counseling<br>* Other names: Non applicable.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose Infusion Rate by euglycemic-hyperinsulinic clamp |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hepatic parameters |  | 6 months | 
| inflammation markers | IL-6, TNF alpha, CRP | 6 months | 
| Adipokins markers | adiponectin, PAI1, leptin | 6 months | 
| SHBG |  | 6 months | 
| HOMA-IR |  | 6 months | 
| Hepatic iron overload (MRI) | transaminase (ALT, AST), gamma GT | 6 months | 
| Abdominal and sub-cutaneous fat surface (MRI) |  | 6 months | 
| iron parameters | serum iron, ferritin, saturation of transferrin | at 6 months | 
| lipid profile | HDL-c, LDL-c, triglycerides | at 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phlebotomy, Insulin Resistance, Iron Overload