Clinical Trials

MainTitle

Assessing the Severity of Metabolic-related Liver Injuries in Aging HIV-monoinfected Patients (ANRS ECHAM)

This study has been completed
Sponsor
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)


Information provided by (Responsible Party)
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier
NCT02093754

First received: January 17, 2014
Last updated: July 11, 2016
Last Verified: July 2016
History of Changes
Purpose

Purpose

This study will allow to assess liver related injuries in HIV patients.

Condition Intervention
HIV Infection
Liver Injuries

Procedure : MRI and biopsy

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Assessing the Severity of Metabolic-related Liver Injuries in Aging HIV-monoinfected Patients: a European Multicentre Study

Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures

  • Percentage of steatosis detected by MRI [ Time Frame: Within 6 months after all patients have completed MRI ]
Secondary Outcome Measures:
  • Percentage of fibrosis or cirrhosis using non invasive markers and concordance of non invasive markers [ Time Frame: Within 6 months after all patients have completed the study ]
  • Risk factors (age, duration of infection, treatment, clinical and biological metabolic and adipose tissue parameters) of liver injuries [ Time Frame: Within 6 months after all patients have completed the study ]
  • Independent risk factors of NAFLD, NASH and fibrosis (including markers of insulin resistance, inflammatory cytokines, markers of immune activation, adipokines) [ Time Frame: Within 6 months after all patients have completed the study ]
  • Establish a diagnosis score based on biomarkers of liver injuries (Adiponectin, leptin, IL6, CRP, CD14) [ Time Frame: Within 6 months after all patients have completed the study ]
    Quantifiable levels of serum adiponectin, serum leptin, serum HS-IL-6, HS-CRP, serum s-CD14 will be measured.
  • Description of pathogenetic factors and correlates with autophagy in liver biopsies of patients with evidence for liver fibrosis [ Time Frame: Within 6 months after all patients have completed the study ]
    Autophagosome formation in the liver biopsies (only for patients presenting liver fibrosis equal or > 2 will be quantified.
  • Identification of features of the adaptive immune system associated to NAFLD, NASH and fibrosis (T cell activation, surface expression of Treg, NK cells, NKT cells) [ Time Frame: Within 6 months after all patients have completed the study ]
    Quantifiable levels of T cell activation (in PBMC), Frequency and phenotype of Tregs (in PBMC), Quantifiable levels of NK cells (in PBMC), Quantifiable levels of Th17 and γδ T cell (in PBMC), Quantifiable levels of Plasma LPS and LPB (sCD163, CD26, Cytokeratin 18) will be measured.
  • Impact of IL28B and PNPLA3 genetic polymorphisms on the severity of liver steatosis, inflammation and fibrosis [ Time Frame: Within 6 months after all patients have completed the study ]
  • Percentage of patients with NASH, fibrosis and cirrhosis on liver biopsy [ Time Frame: Within 6 months after all patients have completed the study ]

Enrollment: 460
Study Start Date: May 2014
Study Completion Date: March 2016
Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)

Detailed Description:

This study is a cross-sectional, multicentre study including 7 centres from 3 European countries (Belgium, France, Germany).
The maximum duration of the study for each patient will be 4 months, consisting of:

  • a screening visit,
  • an inclusion visit to perform the biologic tests and exams necessary for the study, within 1 month after the screening visit,
  • a result delivery visit within 1 month after inclusion visit, to disclose results of previous investigations. Patients with one or two non invasive markers suggesting significant fibrosis (≥F2) will be invited for liver biopsy within the next 2 months.
  • a "liver biopsy" visit, within 2 months after visit 2, liver biopsy in selected and
consented patients

Eligibility

Eligibility

Ages Eligible for Study: 40 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

  1. Age ≥40 years
  2. Infection with HIV-1
  3. Cumulative exposure to cART for at least 5 years and currently under cART
  4. Viral load < 400 copies/mL
  5. CD4 count > 100 CD4/mm3
  6. Female may be eligible to enter and participate in the study if she:
    • is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or
    • is of child-bearing potential with a negative blood pregnancy test at screening visit
  7. Informed consent signed prior to any study procedure
  8. To be covered by a medical insurance (only for French centres)
  9. Presence of:
    • the metabolic syndrome as defined by the most recent international consensus definition (Alberti et al. Circulation 2009) including three components among the following criteria:
      • visceral obesity (waist circumference: Europeans and Africans ≥ 94 cm for men and ≥ 80 cm for women, Americans ≥ 102 cm for men and ≥ 88 cm for women, Asians ≥ 90 cm for men and ≥ 80 cm for women)
      • blood glucose ≥ 1 g/L (5,6 mmol/L) or anti-diabetic treatment,
      • serum triglycerides ≥ 1,5 g/L (1,7 mmol/L) or hypertriglycerides treatment,
      • serum HDL cholesterol < 0,4 g/L (1 mmol/L) for men and < 0,5 g/L (1,3 mmol/L) for women or hypercholesterolemia treatment,
      • blood pressure (Diastolic ≥130 mmHg and/or Systolic ≥ 85 mmHg) or antihypertensive treatment
    • and/or clinical lipoatrophy and/or lipohypertrophy using clinical questionnaires used and validated in previous published studies (ANRS 121 Hippocampe trial),
    • and/or chronic elevated transaminases ≥ 1.5 ULN and / or GGT ≥ 2 ULN confirmed by two blood samples within at least three-month interval over twelve months prior screening visit.

  • Exclusion Criteria:
  • Coinfection with hepatitis B (positive HBs antigen or isolated positive HBc antibody with positive PCR)
  • Positive HCV serology
  • Coinfection HIV-1 and HIV-2
  • Use of intravenous drugs within the last six months
  • Excessive alcohol intake (male > 50 g/d, female > 40 g/d)
  • Other causes of liver diseases i.e: viral hepatitis, hemochromatosis, Wilson disease, autoimmune hepatitis, primary or secondary biliary cirrhosis, primary or secondary cholangitis, α1 antitrypsine deficiency
  • Other causes of liver steatosis: current steroid therapy, current therapy with amiodarone, tamoxifen, methotrexate, nifedipine, or hycanthone; history of cancer chemotherapy; short bowel syndrome, polycystic ovarian syndrome, Weber-Christian disease
  • Active opportunistic infection except for candida oesophagitis
  • Current Cancer
  • Pregnancy
  • Decompensated heart failure
  • Subject under legal guardianship
  • Inability to give informed consent or incapacitation
  • Contra-indication to MRI: pace-maker, neurovascular surgery, intraocular materials, cochlear implant, severe claustrophobia
  • Participation in another study with an ongoing exclusion period at screening

    contacts and locations

    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: NCT02093754

    Locations

    Belgium
    CHU Brussels
    Brussels, Belgium
    France
    Hôpital la Salpêtrière
    Paris, France
    Hôpital Saint Antoine
    Paris, France
    Germany
    Medical Center for Infectious Diseases
    Berlin, Germany
    Center for HIV and Hepato-Gastroenterology
    Düsseldorf, Germany
    University Medical Center
    Hamburg, Germany
    Hannover Medical School
    Hannover, Germany

    Sponsors and Collaborators

    French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

    Investigators

    Principal Investigator: Maud LEMOINE, MD Medical Research Council
    More Information

    More Information


    Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)  
    ClinicalTrials.gov Identifier: NCT02093754   History of Changes  
    Other Study ID Numbers: ECHAM  
      2012-A01670-43  
    Study First Received: January 17, 2014  
    Last Updated: July 11, 2016  

    Additional relevant MeSH terms:
    Wounds and Injuries
    HIV Infections

    ClinicalTrials.gov processed this data on December 13, 2017
    This information is provided by ClinicalTrials.gov.