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

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

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.

Study Overview

• Status: Completed
• Conditions: Liver Cirrhosis; Iron Overload
• Intervention / Treatment: Procedure: Phlebotomy; Behavioral: Lifestyle and diet advices

Detailed Description

Non applicable

• Study Type: Interventional
• Enrollment (Actual): 274
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63058
    • Clermont-Ferrand University Hospital
  • La Roche Sur Yon, France, 85925
    • La Roche Sur Yon Hospital
  • Lorient, France, 56100
    • Lorient Hospital
  • Rennes, France, 35000
    • Service des maladies du foie - Hôpital Pontchaillou
  • Saint-Malo, France, 35400
    • Saint-Malo Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Collaborators: Ministry of Health, France
• Investigators: Study Chair: Eric BELLISSANT, MD, PhD, Rennes University Hospital; Principal Investigator: Fabrice LAINE, MD, Rennes University Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: January 8, 2010
• First Submitted That Met QC Criteria: January 8, 2010
• First Posted (Estimate): January 11, 2010

Study Record Updates

• Last Update Posted (Actual): May 23, 2023
• Last Update Submitted That Met QC Criteria: May 22, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Phlebotomy; Dysmetabolic liversiderosis; Hepatic Iron overload
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Metabolic Diseases; Liver Diseases; Iron Metabolism Disorders; Fibrosis; Liver Cirrhosis; Iron Overload
• Other Study ID Numbers: EUDRACT 2009-A00831-56; PHRC / 09-02 (Other Identifier: Sponsor)