Clinical trial NCT01045525: Phlebotomy and Lifestyle and Diet Advices vs Lifestyle and Diet Advices Only in Patients With Dysmetabolic Liversiderosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Liver Cirrhosis
Iron Overload
Keywords: Phlebotomy
Dysmetabolic liversiderosis
Hepatic Iron overload
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2010-01-11
Enrollment: 274
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Fasting blood glycemia (T0 of Oral Glucose Tolerance Test)
timeFrame: 12 months
Secondary outcomes:
measure: Rate of Body mass index > 25 kg/m²
timeFrame: 12 months
measure: Rate of systolic blood pressure ≥ 130mmHg or diastolic blood pressure ≥ 85 mmHg or antihypertensive treatment
timeFrame: 12 months
measure: Rate of abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women)
timeFrame: 12 months
measure: Rate of fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment
timeFrame: 12 months
measure: Rate of fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment
timeFrame: 12 months
measure: Rate of fasting glycemia ≥ 5.6 mmol/L
timeFrame: 12 months
measure: HbA1c value
timeFrame: 12 months
measure: Quality of life estimated with SF36 form and tolerance to treatment
timeFrame: 12 months
measure: Insulinoresistance indexes calculated at T0 and T30 min of Oral Glucose Tolerance Test (OGTT)
timeFrame: 12 months
measure: Biological markers: CRP, hyaluronic acid, fibrometer
timeFrame: 12 months
measure: myocardial deformation
timeFrame: 12 months
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: Clermont-Ferrand University Hospital
city: La Roche Sur Yon
country: France
facility: La Roche Sur Yon Hospital
city: Lorient
country: France
facility: Lorient Hospital
city: Rennes
country: France
facility: Service des maladies du foie - Hôpital Pontchaillou
city: Saint-Malo
country: France
facility: Saint-Malo Hospital
Study officials:
affiliation: Rennes University Hospital
name: Fabrice LAINE, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rennes University Hospital
name: Eric BELLISSANT, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.