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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: June 2015

Detailed Description

Non applicable

Interventions

  • Procedure: Phlebotomy
    • From 300 to 400mL for women; From 350 to 450mL for men
  • Behavioral: Lifestyle and diet advices
    • 2 Booklets with Dietary and physical activity advices

Arms, Groups and Cohorts

  • Experimental: Phlebotomy + lifestyle and diet advices
  • Active Comparator: Lifestyle and diet advices

Clinical Trial Outcome Measures

Primary Measures

  • Fasting blood glycemia (T0 of Oral Glucose Tolerance Test)
    • Time Frame: 12 months

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Rennes University Hospital
  • Collaborator
    • Ministry of Health, France
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Fabrice LAINE, MD, Principal Investigator, Rennes University Hospital
    • Eric BELLISSANT, MD, PhD, Study Chair, Rennes University Hospital

Citations Reporting on Results

Laine F, Ruivard M, Loustaud-Ratti V, Bonnet F, Cales P, Bardou-Jacquet E, Sacher-Huvelin S, Causse X, Beusnel C, Renault A, Bellissant E, Deugnier Y; Study Group. Metabolic and hepatic effects of bloodletting in dysmetabolic iron overload syndrome: A randomized controlled study in 274 patients. Hepatology. 2017 Feb;65(2):465-474. doi: 10.1002/hep.28856. Epub 2016 Nov 10.

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