Nonalcoholic Steatohepatitis in HIV Mono-infection: Exploring Non-invasive Methods for Diagnosis and the Therapeutic Role of Vitamin E

NCT03988725 | Completed

• 1 other identifier: CTNPT 024
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

Effective combination antiretroviral therapy (cART) has resulted in a dramatic reduction in AIDS mortality. Over the last decade, the proportion of deaths caused by liver-related etiologies, including co-infection with hepatitis C (HCV) and hepatitis B (HBV) viruses, alcohol abuse, and fatty liver, has increased between 8 to 10 fold in the post-cART era while AIDS-related mortality has fallen more than 90-fold. HIV infection without viral hepatitis is also at risk for liver disease. Indeed, HIV mono-infected persons experience common conditions, such as obesity, diabetes and dyslipidemia, which are risk factors for non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common liver disease in Canada. It is a fatty infiltration of the liver that is not evolutive per se, but it is the first histopathological step for non-alcoholic steatohepatitis (NASH), a progressive disease characterized by much inflammation leading to liver fibrosis and cirrhosis. NASH may be frequent in the setting of HIV mono-infection due to excess of metabolic risk factors, long-term cART, HIV itself and lipodystrophy. An early diagnosis of NASH is essential to establish a prognosis and initiate interventions to reduce progression of liver disease towards cirrhosis. Early diagnosis of NASH is critical for targeting metabolic and hepatologic interventions, which can impact on progression to cirrhosis and end-stage complications. Non-invasive tools for liver fibrosis and NASH, including Fibroscan/CAP and CK-18, are accurate and ideal for screening and serial monitoring. No study has specifically targeted the non-invasive diagnosis of NASH in HIV mono-infected patients. There has been no study about the use of CK-18 as a biomarker for NASH in the setting of HIV mono-infection. Furthermore, CAP has never been applied to this specific population. Finally, there is no data about the potential beneficial therapeutic effect of vitamin E on NASH associated to HIV infection. The investigators hypothesize that CK-18 and Fibroscan/CAP can be used as non-invasive tests to diagnose NASH in HIV mono-infected persons. Likewise, the investigators hypothesize that there will be a significant prevalence of NASH diagnosed by non-invasive tools among patients with HIV mono-infection. The investigators further hypothesize that a 6 months treatment trial with vitamin E supplementation will improve non-invasive diagnostic tests, and/or the metabolic and hepatic profile in HIV mono-infected patients with a non-invasive diagnosis of NASH.

Conditions

HIV Mono Infection

Outcome Measures

Primary Outcomes (3)

• Improvement of NASH diagnosed by non-invasive methods

  Assessed by i) difference in AST and/or ALT

  6 months

• Improvement of NASH diagnosed by non-invasive methods

  Assessed by ii) difference in Fibroscan/CAP measurements

  6 months

• Improvement of NASH diagnosed by non-invasive methods

  Assessed by iii) difference in CK-18 levels

  6 months

Secondary Outcomes (3)

• Change in metabolic markers

  6 months

• Change in metabolic markers

  6 months

• Change in metabolic markers

  6 months

Study Arms (1)

Vitamin E intervention

EXPERIMENTAL

All study participants receive Vitamin E 800 IU once daily for 6 months

Dietary Supplement: Vitamin E

Interventions

Vitamin E DIETARY_SUPPLEMENT

Vitamin E 800 IU once daily

Vitamin E intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed positive serology for HIV mono-infection and 18 years or older; valid Fibroscan/CAP;
• Able to provide informed consent, signing forms available in French or English.
• Fatty liver (CAP\>237.8 dB/m) AND CK-18 levels \> 246 U/L OR
• Fatty liver (CAP\>237.8 dB/m) AND CK-18 149 U/L + chronically elevated liver function tests (transaminases) + at least 1 metabolic risk factor (among diabetes, insulin resistance, dyslipidemia or overweight).

You may not qualify if:

• Co-infection with HCV or HBV (presence of serum HCV-Ab or HbsAg); HCC, liver transplantation
• Significant alcohol consumption, as per AASLD guidelines on NAFLD: "ongoing or recent alcohol consumption \> 21 drinks on average per week in men and \> 14 drinks on average per week in women"
• Patients taking anticoagulants (warfarin, heparin)
• Patients undergoing chemotherapy or radiotherapy for cancer
• History of diagnosis of prostate cancer
• Planning to become, suspected to be, pregnant or breastfeeding

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead
• CIHR Canadian HIV Trials Network: collaborator

Study Sites (1)

Chronic Viral Illness Center at Royal Victoria Hospital in McGill university Health Center

Montreal, Quebec, Canada

Location

MeSH Terms

Interventions

Vitamin E

Intervention Hierarchy (Ancestors)

Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Giada Sebastiani

  Chronic Viral Illness Service, MUHC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 12, 2019
• First Posted: June 17, 2019
• Study Start: November 11, 2014
• Primary Completion: March 11, 2019
• Study Completion: March 11, 2019
• Last Updated: June 17, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)