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出境医 / 临床实验 / Nonalcoholic Steatohepatitis in HIV Mono-infection: Exploring Non-invasive Methods for Diagnosis and the Therapeutic Role of Vitamin E

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

Study Description
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.

Condition or disease Intervention/treatment Phase
HIV Mono Infection Dietary Supplement: Vitamin E Not Applicable

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Nonalcoholic Steatohepatitis in HIV Mono-infection: Exploring Non-invasive Methods for Diagnosis and the Therapeutic Role of Vitamin E
Actual Study Start Date : November 11, 2014
Actual Primary Completion Date : March 11, 2019
Actual Study Completion Date : March 11, 2019
Arms and Interventions
Arm Intervention/treatment
Experimental: Vitamin E intervention
All study participants receive Vitamin E 800 IU once daily for 6 months
Dietary Supplement: Vitamin E
Vitamin E 800 IU once daily

Outcome Measures
Primary Outcome Measures :
  1. Improvement of NASH diagnosed by non-invasive methods [ Time Frame: 6 months ]
    Assessed by i) difference in AST and/or ALT

  2. Improvement of NASH diagnosed by non-invasive methods [ Time Frame: 6 months ]
    Assessed by ii) difference in Fibroscan/CAP measurements

  3. Improvement of NASH diagnosed by non-invasive methods [ Time Frame: 6 months ]
    Assessed by iii) difference in CK-18 levels


Secondary Outcome Measures :
  1. Change in metabolic markers [ Time Frame: 6 months ]
    HOMA

  2. Change in metabolic markers [ Time Frame: 6 months ]
    Cholesterol or triglyceride levels

  3. Change in metabolic markers [ Time Frame: 6 months ]
    Weight and height will be combined to report BMI in kg/m^2


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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
Contacts and Locations

Locations
Layout table for location information
Canada, Quebec
Chronic Viral Illness Center at Royal Victoria Hospital in McGill university Health Center
Montréal, Quebec, Canada
Sponsors and Collaborators
McGill University Health Centre/Research Institute of the McGill University Health Centre
CIHR Canadian HIV Trials Network
Investigators
Layout table for investigator information
Principal Investigator: Giada Sebastiani Chronic Viral Illness Service, MUHC
Tracking Information
First Submitted Date  ICMJE June 12, 2019
First Posted Date  ICMJE June 17, 2019
Last Update Posted Date June 17, 2019
Actual Study Start Date  ICMJE November 11, 2014
Actual Primary Completion Date March 11, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 14, 2019)
  • Improvement of NASH diagnosed by non-invasive methods [ Time Frame: 6 months ]
    Assessed by i) difference in AST and/or ALT
  • Improvement of NASH diagnosed by non-invasive methods [ Time Frame: 6 months ]
    Assessed by ii) difference in Fibroscan/CAP measurements
  • Improvement of NASH diagnosed by non-invasive methods [ Time Frame: 6 months ]
    Assessed by iii) difference in CK-18 levels
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 14, 2019)
  • Change in metabolic markers [ Time Frame: 6 months ]
    HOMA
  • Change in metabolic markers [ Time Frame: 6 months ]
    Cholesterol or triglyceride levels
  • Change in metabolic markers [ Time Frame: 6 months ]
    Weight and height will be combined to report BMI in kg/m^2
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nonalcoholic Steatohepatitis in HIV Mono-infection: Exploring Non-invasive Methods for Diagnosis and the Therapeutic Role of Vitamin E
Official Title  ICMJE Nonalcoholic Steatohepatitis in HIV Mono-infection: Exploring Non-invasive Methods for Diagnosis and the Therapeutic Role of Vitamin E
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV Mono Infection
Intervention  ICMJE Dietary Supplement: Vitamin E
Vitamin E 800 IU once daily
Study Arms  ICMJE Experimental: Vitamin E intervention
All study participants receive Vitamin E 800 IU once daily for 6 months
Intervention: Dietary Supplement: Vitamin E
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 14, 2019)
27
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 11, 2019
Actual Primary Completion Date March 11, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03988725
Other Study ID Numbers  ICMJE CTNPT 024
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Giada Sebastiani, McGill University Health Centre/Research Institute of the McGill University Health Centre
Study Sponsor  ICMJE McGill University Health Centre/Research Institute of the McGill University Health Centre
Collaborators  ICMJE CIHR Canadian HIV Trials Network
Investigators  ICMJE
Principal Investigator: Giada Sebastiani Chronic Viral Illness Service, MUHC
PRS Account McGill University Health Centre/Research Institute of the McGill University Health Centre
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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