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

Sponsor

ANRS, Emerging Infectious Diseases (Other)

Overall Status

Completed

CT.gov ID

NCT02093754

Collaborator

(none)

460

Enrollment

Locations

Duration (Months)

65.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
HIV Infection Liver Injuries	Procedure: MRI and biopsy	N/A

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

Study Design

Study Type:

Interventional

Actual Enrollment :

460 participants

Allocation:

N/A

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

Study Start Date :

May 1, 2014

Actual Primary Completion Date :

Mar 1, 2016

Actual Study Completion Date :

Mar 1, 2016

Outcome Measures

Primary Outcome Measures

Percentage of steatosis detected by MRI [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 [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 [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) [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) [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 [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) [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 [Within 6 months after all patients have completed the study]
Percentage of patients with NASH, fibrosis and cirrhosis on liver biopsy [Within 6 months after all patients have completed the study]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥40 years
Infection with HIV-1
Cumulative exposure to cART for at least 5 years and currently under cART
Viral load < 400 copies/mL
CD4 count > 100 CD4/mm3
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

Informed consent signed prior to any study procedure
To be covered by a medical insurance (only for French centres)
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

Locations

	Site	City	Country
1	CHU Brussels	Brussels	Belgium
2	Hôpital la Salpêtrière	Paris	France
3	Hôpital Saint Antoine	Paris	France
4	Medical Center for Infectious Diseases	Berlin	Germany
5	Center for HIV and Hepato-Gastroenterology	Düsseldorf	Germany
6	University Medical Center	Hamburg	Germany
7	Hannover Medical School	Hannover	Germany

Sponsors and Collaborators

ANRS, Emerging Infectious Diseases

Investigators

Principal Investigator: Maud LEMOINE, MD, Medical Research Council

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

ANRS, Emerging Infectious Diseases

ClinicalTrials.gov Identifier:

NCT02093754

Other Study ID Numbers:

ECHAM
2012-A01670-43

First Posted:

Mar 21, 2014

Last Update Posted:

Jul 12, 2016

Last Verified:

Jul 1, 2016

Additional relevant MeSH terms:

Wounds and Injuries

Study Results

No Results Posted as of Jul 12, 2016