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

Liver Cirrhosis Clinical Trial

— SAIGNEES  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01045525
• Other study ID #: EUDRACT 2009-A00831-56
• Secondary ID: PHRC / 09-02
• Status: Completed
• Phase: Phase 3
• Start date: January 2010
• Est. completion date: December 2015

Study information

• Verified date: May 2023
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Non applicable

Recruitment information / eligibility

• Status: Completed
• Enrollment: 274
• Est. completion date: December 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Iron Overload
• Liver Cirrhosis

Intervention

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

Locations

Country	Name	City	State
France	Clermont-Ferrand University Hospital	Clermont-Ferrand
France	La Roche Sur Yon Hospital	La Roche Sur Yon
France	Lorient Hospital	Lorient
France	Service des maladies du foie - Hôpital Pontchaillou	Rennes
France	Saint-Malo Hospital	Saint-Malo

Sponsors (2)

Lead Sponsor	Collaborator
Rennes University Hospital	Ministry of Health, France

Country where clinical trial is conducted

France, 

References & Publications (1)

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 ran — View Citation

Outcome

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