Effects of Phlebotomy on Insulin Sensitivity in Insulin Resistance-associated Hepatic Iron Overload Patients (SAINPOS)

The purpose of this study is to evaluate efficacy of phlebotomy on insulin sensitivity as evaluated by euglycemic-hyperinsulinic clamp in insulin resistance-associated hepatic iron overload patients.

Study Overview

• Status: Completed
• Conditions: Insulin Resistance; Iron Overload
• Intervention / Treatment: Procedure: phlebotomy; Behavioral: dietary and lifestyle counseling

Detailed Description

The main objective of this study is to evaluate in patients with HSD effects of treatment with phlebotomy rules with lifestyle and dietary rules versus lifestyle modifications alone on peripheral insulin resistance (assessed by hyperinsulinemic clamp).

Secondary objectives are:

• to study in all patients with HSD the relationship between the amount of iron intrahepatic and degree of peripheral insulin resistance and liver before therapeutic intervention.

• to study and compare the effects of phlebotomy treatment versus no treatment on:

  • Plasma levels of adipocytokines,
  • Plasma concentrations of inflammatory markers and markers of insulin resistance,
  • The serum ferritin,
  • The post-hepatic clearance of insulin,
  • The surface of the abdominal visceral fat and subcutaneous abdominal.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Nantes, France, F-44000
    • CHU
  • Rennes, France, F-35203
    • CHU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age between 18 and 70 years
• Ferritin between 450 and 1000 µg/L
• Hepatic iron overload proved by MRI (CHF >36 µmol/g)
• Body mass index > 25 kg/m²
• Fasting glycemia <1,26 g/L
• HbA1c < 6,5%
• Signed written and informed consent

Exclusion Criteria:

• Other causes of hyperferritinemia:

  • Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases
  • Hyperferritinemia-cataract syndrome (familial cataract or personal history of cataract before 50 years old)
  • Low ceruloplasmin level
  • Porphyria (cutaneous signs)
  • Haemochromatosis established by the genotype (C282Y homozygous or C282Y/H63D coumpound heterozygous genotypes)

• Contraindication of phlebotomy

  • Haemoglobin <13,5 g/dL (threshold established by the Etablissement Français du Sang)
  • Heart failure or coronary heart diseases
  • Hepatic failure, renal (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea)
  • Poor venous system
• Viral, immune, genetic, vascular, malignant or toxic chronic hepatic disease
• Alcohol consumption more than 21 doses per week during 5 years or more
• Type 1 or type 2 diabetes
• Oral anti-diabetic, corticoids or immune suppressor drugs
• Hepatic severe disease
• Claustrophobia, having a pace-maker or intracerebral clips
• Subjects deprived of their liberty by judicial or administrative decision, subjects that are not affiliated to social security or topics exclusion period of a previous study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phlebotomy; phlebotomy associated with dietary and lifestyle counseling	Procedure: phlebotomy; 7 ml/kg without exceeding 500 mL; Other Names: Non applicable.; Behavioral: dietary and lifestyle counseling; dietary and lifestyle counseling; Other Names: Non applicable.
Active Comparator: Lifestyle counseling; dietary and lifestyle counseling	Behavioral: dietary and lifestyle counseling; dietary and lifestyle counseling; Other Names: Non applicable.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Glucose Infusion Rate by euglycemic-hyperinsulinic clamp	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HOMA-IR		6 months
hepatic parameters		6 months
inflammation markers	IL-6, TNF alpha, CRP	6 months
Adipokins markers	adiponectin, PAI1, leptin	6 months
SHBG		6 months
Hepatic iron overload (MRI)	transaminase (ALT, AST), gamma GT	6 months
Abdominal and sub-cutaneous fat surface (MRI)		6 months
iron parameters	serum iron, ferritin, saturation of transferrin	at 6 months
lipid profile	HDL-c, LDL-c, triglycerides	at 6 months

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Investigators: Principal Investigator: Fabrice BONNET, MD, PHD, Rennes University Hospital; Study Chair: Eric Bellissant, MD, PhD, RennesUniversity Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: May 17, 2011
• First Submitted That Met QC Criteria: April 4, 2012
• First Posted (Estimate): April 6, 2012

Study Record Updates

• Last Update Posted (Estimate): June 15, 2016
• Last Update Submitted That Met QC Criteria: June 14, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Insulin Resistance; Phlebotomy; Iron Overload
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Iron Metabolism Disorders; Hyperinsulinism; Iron Overload; Insulin Resistance
• Other Study ID Numbers: 2008-A00636-49; PHRC/07-05 (Other Identifier: Rennes University Hospital); CIC0203/070 (Other Identifier: Center for Clinical Research of Rennes)