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

HIV Infection Clinical Trial

— ANRS ECHAM  

Official title:

Assessing the Severity of Metabolic-related Liver Injuries in Aging HIV-monoinfected Patients: a European Multicentre Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02093754
• Other study ID #: ECHAM
• Secondary ID: 2012-A01670-43
• Status: Completed
• Phase: N/A
• First received: January 17, 2014
• Last updated: July 11, 2016
• Start date: May 2014
• Est. completion date: March 2016

Study information

• Verified date: July 2016
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 460
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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:

1. Coinfection with hepatitis B (positive HBs antigen or isolated positive HBc antibody with positive PCR)

2. Positive HCV serology

3. Coinfection HIV-1 and HIV-2

4. Use of intravenous drugs within the last six months

5. Excessive alcohol intake (male > 50 g/d, female > 40 g/d)

6. Other causes of liver diseases i.e: viral hepatitis, hemochromatosis, Wilson disease, autoimmune hepatitis, primary or secondary biliary cirrhosis, primary or secondary cholangitis, a1 antitrypsine deficiency

7. 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

8. Active opportunistic infection except for candida oesophagitis

9. Current Cancer

10. Pregnancy

11. Decompensated heart failure

12. Subject under legal guardianship

13. Inability to give informed consent or incapacitation

14. Contra-indication to MRI: pace-maker, neurovascular surgery, intraocular materials, cochlear implant, severe claustrophobia

15. Participation in another study with an ongoing exclusion period at screening

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• HIV Infection
• HIV Infections
• Liver Injuries
• Wounds and Injuries

Intervention

Procedure:
• MRI and biopsy

Locations

Country	Name	City	State
Belgium	CHU Brussels	Brussels
France	Hôpital la Salpêtrière	Paris
France	Hôpital Saint Antoine	Paris
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

Sponsors (1)

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

Countries where clinical trial is conducted

Belgium,  France,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of steatosis detected by MRI		Within 6 months after all patients have completed MRI	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Establish a diagnosis score based on biomarkers of liver injuries (Adiponectin, leptin, IL6, CRP, CD14)	Quantifiable levels of serum adiponectin, serum leptin, serum HS-IL-6, HS-CRP, serum s-CD14 will be measured.	Within 6 months after all patients have completed the study	No
Secondary	Description of pathogenetic factors and correlates with autophagy in liver biopsies of patients with evidence for liver fibrosis	Autophagosome formation in the liver biopsies (only for patients presenting liver fibrosis equal or > 2 will be quantified.	Within 6 months after all patients have completed the study	No
Secondary	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)	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 ?d T cell (in PBMC), Quantifiable levels of Plasma LPS and LPB (sCD163, CD26, Cytokeratin 18) will be measured.	Within 6 months after all patients have completed the study	No
Secondary	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	No
Secondary	Percentage of patients with NASH, fibrosis and cirrhosis on liver biopsy		Within 6 months after all patients have completed the study	No