MEPHISTO (Macrophage Phenotype In Metabolic Syndrome With Iron Overload)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by University Hospital, Clermont-Ferrand
Sponsor:
Collaborator:
Institut National de la Recherche Agronomique
Information provided by (Responsible Party):
University Hospital, Clermont-Ferrand
ClinicalTrials.gov Identifier:
NCT02066012
First received: February 14, 2014
Last updated: February 17, 2014
Last verified: February 2014
  Purpose

Dysmetabolic iron overload syndrome (DIOS), is a frequent hepatic iron overload associated with metabolic syndrome. We hypothesize that this mild iron overload can induce a increased macrophagic polarization towards inflammatory types, thereby contributing to cardiovascular risk. Our main objective is to highlight the influence of iron overload on polarization capacity of monocytes into alternative macrophages (called M2). We therefore compare phenotypic markers of monocytes/macrophages between subjects with DIOS, metabolic syndrome without iron overload and lean subjects.


Condition Intervention
Dysmetabolic Iron Overload Syndrome
Metabolic Syndrome X
Other: dysmetabolic iron overload syndrome

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Impact of Dysmetabolic Iron Overload Syndrome on Polarization Capacity of Macrophages

Resource links provided by NLM:


Further study details as provided by University Hospital, Clermont-Ferrand:

Primary Outcome Measures:
  • Expression (RNA) of macrophagic polarization markers [ Time Frame: at day 1 ] [ Designated as safety issue: No ]
    Expression (RNA) of macrophagic polarization markers (MR, CD200R, F13A1, CD163, AMAC1, TGFβ), among subjects with or without iron overload


Secondary Outcome Measures:
  • characteristics of the subjects [ Time Frame: at day 1 ] [ Designated as safety issue: No ]
    Statistical relationships between monocyte phenotype and clinical (metabolic abnormalities) or biological (level of iron overload, oxidative stress and insulino-resistance) characteristics of the subjects.


Estimated Enrollment: 60
Study Start Date: February 2014
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
group DIOS
group DIOS composed of subjects with dysmetabolic hepatosiderosis
Other: dysmetabolic iron overload syndrome
group M
group M composed of subjects with metabolic syndrom without iron overload
Other: dysmetabolic iron overload syndrome
group T
group T composed of lean subjects
Other: dysmetabolic iron overload syndrome

Detailed Description:

MEPHISTO is a pathophysiological, transverse, case-control, single-center study (university hospital, Clermont-Ferrand, France). No intervention (drug or nutritional) is conducted as part of this study and the participants are not subject to any exclusion period. Our objective is to investigate the effects of iron overload on monocyte/macrophage polarization and its relations with the cardiovascular risk factors.

We study 60 subjects divided into 3 groups of 20 participants :

  • group DIOS composed of subjects with dysmetabolic hepatosiderosis
  • group M composed of subjects with metabolic syndrom without iron overload
  • group T composed of lean subjects DIOS group participants were selected among patients recently diagnosed as DIOS, without any secondary hyperferritinemia and with hepatic iron overload proved by liver MRI.

Recruitement of group DIOS was carried out in the internal medicine service. Subjects of group M and DIOS come from the file of volunteers from the center of clinical investigation (CIC-501, Clermont-Ferrand). Subject of group M to group DIOS are matched by age, gender (+/- 5 kg/m²) and BMI. Subjects of group T to group DIOS are matched by age and gender. As no direct benefit is expected for the participants, they receive a lump sum compensation of 50 euros.

Each participant undergoes only a 1 hour consultation including a clinical examination and blood sample.

We focus on clinical parameters of the metabolic syndrome (waist size, BMI, blood pressure) and on seeking exclusion factors (infection, neoplasia, anti-inflammatory drugs). Due to their potential influence on inflammation and oxidant stress, these factors, as same as smoking were excluded.

Blood sample will be used to perform:

  • classical laboratory test (blood count, reticulocytes, ASAT, ALAT, LDH, lipid profile, glycemia, insulinemia, TSH, , vitamin D, ferritin, transferrin saturation, CRP),
  • specific dosages (IL-6, TNFalpha, hepcidine) by ELISA,
  • monocyte phenotype ( CD14, CD16, CD 163, MR) by FACS (Fluorescence Activated Cell Sorting),
  • measurement of the gene expression from monocytes and macrophages after culturing by real-time PCR.

Our main analysis focus on ex vivo polarization of monocytes into alternative macrophages (M2) and phenotypic characterization. Before and after culturing monocytes with (to induce M2 macrophage) or without IL-4 (to induce resident macrophage), we will measure the expression of phenotypic markers of polarization (MR, CD200R, F13A1, CD163, AMAC1, TGFb), inflammatory markers (TNFα , MCP- 1, IL-6) , oxidative stress markers (HO- 1 ), and markers of iron metabolism (ferroportin, ferritin, hepcidin). We use quantitative PCR microfluidic card (TLDA, Taqman Low-Density Array) to measure gene expression of monocytes and type M2 macrophages. This technique allows screening of expression for 24 genes. Different phases are required: RNA extraction (RNeasy kit, Qiagen), the reverse transcription (RT-PCR kit, HighCap cDNA RT kit, Applied Biosystems), amplification (TaqMan Fast Advanced Master Mix, Applied Biosystems), and finally the study of gene expression (MFC TaqMan Array for GeneEx, Format 24, Applied Biosystems). Our main outcome is capacity of polarization in M2 macrophages evidenced by expression of MR, CD200R, F13A1, CD163, AMAC1, TGFb. Evaluating the influence of iron overload on data from the clinical examination, the results of standard biology and monocyte gene expression is our secondary outcome.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

metabolic syndrome

Criteria

Inclusion Criteria:

  • • 18 years old and over

    • written consent
    • for groups M and HSD at least one criteria of the metabolic syndrome definition according to the International Diabetes Federation
    • for group M only hepatic iron overload mesured by IRM (above 50 µmol/g) hyperferritnemia between 450 and 1500 µg/l
    • for group T only BMI < 25 kg/m² Waist size < 80 cm for women and <94 cm for men

Exclusion Criteria:

  • persons under guardianship
  • pregnancy
  • active smoking
  • current inflammatory or cancerous disease
  • hereditary hemochromatosis
  • use of anti-inflammatory, immunosuppressive or hypoglycaemic drugs
  • hemolysis
  • alcool consumption above 14 doses for women and 21 doses for men per week
  • history of therapeutic phlebotomy
  • inflammatory syndrome with CRP above 15 mg/l
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02066012

Contacts
Contact: Patrick LACARIN 04 73 75 11 95 placarin@chu-clermontferrand.fr

Locations
France
CHU de Clermont-Ferrand Recruiting
Clermont-Ferrand, France, 63003
Contact: Patrick LACARIN    04 73 75 11 95    placarin@chu-celrmontferrand.fr   
Sponsors and Collaborators
University Hospital, Clermont-Ferrand
Institut National de la Recherche Agronomique
Investigators
Principal Investigator: Marc RUIVARD University Hospital, Clermont-Ferrand
  More Information

No publications provided

Responsible Party: University Hospital, Clermont-Ferrand
ClinicalTrials.gov Identifier: NCT02066012     History of Changes
Other Study ID Numbers: CHU-0180, 2013-A01687-38
Study First Received: February 14, 2014
Last Updated: February 17, 2014
Health Authority: France: Ministry of Health

Keywords provided by University Hospital, Clermont-Ferrand:
Dysmetabolic Iron Overload Syndrome
Metabolic Syndrome X
Iron
Monocyte
Macrophage
Polarization

Additional relevant MeSH terms:
Syndrome
Metabolic Syndrome X
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Iron Metabolism Disorders
Iron Overload
Disease
Pathologic Processes
Hyperinsulinism
Iron
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014