Overview

This trial is active, not recruiting.

Conditions liver cirrhosis, iron overload
Treatments phlebotomy, lifestyle and diet advices
Phase phase 3
Sponsor Rennes University Hospital
Collaborator Ministry of Health, France
Start date January 2010
End date December 2015
Trial size 270 participants
Trial identifier NCT01045525, EUDRACT 2009-A00831-56, PHRC / 09-02

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
phlebotomy Non applicable
From 300 to 400mL for women; From 350 to 450mL for men
(Active Comparator)
lifestyle and diet advices Non applicable
2 Booklets with Dietary and physical activity advices

Primary Outcomes

Measure
Fasting blood glycemia (T0 of Oral Glucose Tolerance Test)
time frame: 12 months

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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
Principal investigator Fabrice LAINE, MD
Description Non applicable
Trial information was received from ClinicalTrials.gov and was last updated in July 2015.
Information provided to ClinicalTrials.gov by Rennes University Hospital.