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

Phase 3

Completed

• Conditions: Iron Overload; Liver Cirrhosis
• Interventions: Procedure: Phlebotomy; Behavioral: Lifestyle and diet advices

• Registration Number: NCT01045525
• Lead Sponsor: Rennes University Hospital

Brief Summary

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

Non applicable

Study Timeline

• Study Start: 2010-01
• Study First Submitted: 2010-01-08
• Study First Submitted QC: 2010-01-08
• Study First Posted: 2010-01-11
• Primary Completion: 2015-06
• Study Completion: 2015-12
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-22
• Last Update Posted: 2023-05-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 274

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phlebotomy + lifestyle and diet advices	Phlebotomy	-
Lifestyle and diet advices	Lifestyle and diet advices	-

Primary Outcome Measures

Name	Time	Method
Fasting blood glycemia (T0 of Oral Glucose Tolerance Test)	12 months

Secondary Outcome Measures

Name	Time	Method
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 Body mass index > 25 kg/m²	12 months
Rate of fasting glycemia ≥ 5.6 mmol/L	12 months
Biological markers: CRP, hyaluronic acid, fibrometer	12 months
Rate of systolic blood pressure ≥ 130mmHg or diastolic blood pressure ≥ 85 mmHg or antihypertensive 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
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
myocardial deformation	12 months	Two dimensional (2D) speckle tracking echocardiography (STE)

Trial Locations

Locations (5)

Lorient Hospital; 🇫🇷 Lorient, France

La Roche Sur Yon Hospital; 🇫🇷 La Roche Sur Yon, France

Service des maladies du foie - Hôpital Pontchaillou; 🇫🇷 Rennes, France

Clermont-Ferrand University Hospital; 🇫🇷 Clermont-Ferrand, France

Saint-Malo Hospital; 🇫🇷 Saint-Malo, France