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Raltegravir-based Antiretroviral Versus Maintaining Any Other Antiretroviral Therapy in HIV Mono-infected Patients

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ClinicalTrials.gov Identifier: NCT02210715
Recruitment Status : Unknown
Verified April 2017 by Giada Sebastiani, McGill University Health Centre/Research Institute of the McGill University Health Centre.
Recruitment status was:  Enrolling by invitation
First Posted : August 7, 2014
Last Update Posted : April 25, 2017
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Giada Sebastiani, McGill University Health Centre/Research Institute of the McGill University Health Centre

Brief Summary:
People infected with HIV are living longer thanks to the use of antiretroviral therapy (cART). In aging HIV persons, other factors are associated with early death. One of the major factors is liver disease, which can be due to liver infections or reasons such as fatty liver. Fatty liver in the general population is a serious problem, affecting 30% of Canadian population. A specific type of fatty liver characterized by much inflammation, named nonalcoholic steatohepatitis (NASH) can lead to cirrhosis and death. Persons living with HIV can be at increased risk of NASH because of toxic effect of certain types of cART on the liver, obesity and other metabolic factors (for example diabetes). Some scientific data suggest that newer cART are associated with less fatty liver and liver damage. However, NASH has not been studied in detail in persons living with HIV. One reason for the lack of research is one of the only ways to detect liver disease is to undergo liver biopsy which can be painful and has complications. Recently, a new non-invasive technology (Fibroscan) has been developed which can tell doctors how much a liver is damaged and how much fat it contains without pain or complications. Moreover, a simple test measuring a specific protein in the blood, the cytokeratin 18 (CK-18), can help the diagnosis of NASH. We will study the effect of switching cART to newer types of HIV medication in patients with a non-invasive diagnosis of NASH done by Fibroscan and cytokeratin 18. We expect that switching older cART to less hepatotoxic drugs will lead to improvement of liver damage, fatty liver and NASH diagnosed by Fibroscan and cytokeratin 18. To evaluate this approach we plan to recruit 58 consenting HIV mono infected patients with non-invasive diagnosis of NASH and/or fatty liver with liver damage. Participants will undergo Fibroscan, a blood test for cytokeratin 18, a complete physical examination and laboratory tests every 3 months for 12 months, then at 18 and 24 months. The effect of the switching of HIV medications will be recorded. We anticipate that the current study will provide evidence for reduction of inflammation and liver damage with newer cART for treatment of HIV infection.

Condition or disease Intervention/treatment Phase
HIV Fatty Liver Nonalcoholic Steatohepatitis Drug: Isentress. Other: Continue usual antiretroviral therapy Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 58 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: Randomized Study Comparing Switching to Raltegravir-based Antiretroviral Versus Maintaining Any Other Antiretroviral Therapy in HIV Monoinfected Patients Impact on Fatty Liver and Liver Fibrosis Assessed by Noninvasive Diagnostic Methods
Study Start Date : March 2015
Estimated Primary Completion Date : September 2017
Estimated Study Completion Date : March 2018


Arm Intervention/treatment
Experimental: switch to Isentress
28 subjects will be prescribed Raltegravir at the standard dose of 400 mg p.o. b.i.d. for 24 months.
Drug: Isentress.
28 subjects will change from their normal cART treatment to Raltegravir, which will be given at the standard dose of 400 mg p.o. b.i.d. for 24 months.
Other Name: Raltegravir

Active Comparator: Continue usual antiretroviral therapy
28 subjects will continue with their normal cART treatment, as prescribed by their treating physician.
Other: Continue usual antiretroviral therapy
28 subjects will continue with their normal cART treatment, as prescribed by their treating physician.




Primary Outcome Measures :
  1. improvement of fatty liver or liver fibrosis [ Time Frame: 24 months ]
    Difference in Fibroscan/CAP measurement from baseline to 24 months


Secondary Outcome Measures :
  1. Difference in serum CK-18 levels [ Time Frame: 24 months ]
    Difference in serum CK-18 levels as surrogate diagnostic marker of NASH from baseline to 24 months.

  2. Difference in transaminases levels [ Time Frame: 24 months ]
    Difference in transaminases levels (AST and/or ALT) from baseline to 24 months

  3. Difference in metabolic markers [ Time Frame: 24 months ]
    Difference in metabolic markers (HOMA; cholesterol or triglycerides levels; BMI) from baseline to 24 months.



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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:

  1. 18 years or older
  2. Confirmed positive serology for HIV mono-infection
  3. Valid Fibroscan/CAP results
  4. Able to provide informed consent (available in French or English)
  5. Receiving any approved antiretroviral regimen that does not contain integrase-inhibitor
  6. Evidence of fatty liver (CAP>237.8dB/m) AND/OR evidence of significant liver fibrosis (Fibroscan > 8KPa)
  7. HIV viral suppression (<50 copies/mL) for at least 6 months
  8. No prior evidence of resistance to raltegravir or co-administered nucleoside backbone

Exclusion Criteria:

  1. Clinical evidence of decompensated liver disease at entry (e.g. ascites, bleeding esophageal varices, hepatic encephalopathy, or hepatoma/ hepatocellular carcinoma).
  2. Co-infection with hepatitis C virus (HCV) or hepatitis C virus (HBV) (presence of serum HCV-Ab or HBsAg);
  3. Alpha-fetoprotein (AFP) greater than or equal to 200 ng/mL at screening.
  4. Known or suspected Wilson's disease, alpha-1-antitrypsin deficiency, celiac disease or other cause of chronic liver disease.
  5. Chronic renal insufficiency (eGFR < 20 mL/min) at screening.
  6. Pregnancy and planned pregnancy (not using adequate contraception).
  7. Women who are breastfeeding.
  8. Active opportunistic infection (except oral thrush) or neoplasm (except Kaposi's sarcoma, skin cancer, or cancer of the cervix or anus, unless known or suspected liver metastasis).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02210715


Locations
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Canada, Quebec
McGill University Health Center
Montreal, Quebec, Canada
Sponsors and Collaborators
McGill University Health Centre/Research Institute of the McGill University Health Centre
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Giada Sebastiani, MD McGill University Health Centre/Research Institute of the McGill University Health Centre

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Responsible Party: Giada Sebastiani, Dr Giada Sebastiani MD, McGill University Health Centre/Research Institute of the McGill University Health Centre
ClinicalTrials.gov Identifier: NCT02210715     History of Changes
Other Study ID Numbers: switchMerck
First Posted: August 7, 2014    Key Record Dates
Last Update Posted: April 25, 2017
Last Verified: April 2017
Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases
Anti-Retroviral Agents
Raltegravir Potassium
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action