NCT01045525

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
274

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Jan 2010

Longer than P75 for phase_3

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2010

Completed
7 days until next milestone

First Submitted

Initial submission to the registry

January 8, 2010

Completed
3 days until next milestone

First Posted

Study publicly available on registry

January 11, 2010

Completed
5.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2015

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2015

Completed
Last Updated

May 23, 2023

Status Verified

May 1, 2023

Enrollment Period

5.4 years

First QC Date

January 8, 2010

Last Update Submit

May 22, 2023

Conditions

Liver CirrhosisIron Overload

Keywords

PhlebotomyDysmetabolic liversiderosisHepatic Iron overload

Outcome Measures

Primary Outcomes (1)

  • Fasting blood glycemia (T0 of Oral Glucose Tolerance Test)

    12 months

Secondary Outcomes (11)

  • 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

  • +6 more secondary outcomes

Study Arms (2)

Phlebotomy + lifestyle and diet advices

EXPERIMENTAL
Procedure: Phlebotomy

Lifestyle and diet advices

ACTIVE COMPARATOR
Behavioral: Lifestyle and diet advices

Interventions

PhlebotomyPROCEDURE

From 300 to 400mL for women; From 350 to 450mL for men

Also known as: Non applicable
Phlebotomy + lifestyle and diet advices
Lifestyle and diet advicesBEHAVIORAL

2 Booklets with Dietary and physical activity advices

Also known as: Non applicable
Lifestyle and diet advices

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • 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
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Clermont-Ferrand University Hospital

Clermont-Ferrand, 63058, France

Location

La Roche Sur Yon Hospital

La Roche-sur-Yon, 85925, France

Location

Lorient Hospital

Lorient, 56100, France

Location

Service des maladies du foie - Hôpital Pontchaillou

Rennes, 35000, France

Location

Saint-Malo Hospital

St-Malo, 35400, France

Location

Related 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 randomized controlled study in 274 patients. Hepatology. 2017 Feb;65(2):465-474. doi: 10.1002/hep.28856. Epub 2016 Nov 10.

    PMID: 27685251RESULT

MeSH Terms

Conditions

Liver CirrhosisIron Overload

Interventions

Phlebotomy

Condition Hierarchy (Ancestors)

Liver DiseasesDigestive System DiseasesFibrosisPathologic ProcessesPathological Conditions, Signs and SymptomsIron Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Blood Specimen CollectionSpecimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisPuncturesTherapeuticsSurgical Procedures, OperativeInvestigative Techniques

Study Officials

  • Fabrice LAINE, MD

    Rennes University Hospital

    PRINCIPAL INVESTIGATOR

  • Eric BELLISSANT, MD, PhD

    Rennes University Hospital

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 8, 2010

First Posted

January 11, 2010

Study Start

January 1, 2010

Primary Completion

June 1, 2015

Study Completion

December 1, 2015

Last Updated

May 23, 2023

Record last verified: 2023-05

Locations

FR(5)