Clinical Trials

MainTitle

Impact of Hepatitis C Therapy and Bone Health (HCV)

This study is currently recruiting participants. (see Contacts and Locations)

Verified March 2018 by Dallas VA Medical Center

Sponsor
Dallas VA Medical Center

Collaborator
Merck Sharp & Dohme Corp.

Information provided by (Responsible Party)
Dallas VA Medical Center
ClinicalTrials.gov Identifier
NCT03221582

First received: June 27, 2017
Last updated: March 1, 2018
Last Verified: March 2018
History of Changes
Purpose

Purpose

An evaluation of the impact of Elbasvir and Grazoprevir (EBR/GZR) HCV therapy on the heart risk and bone health of HCV mono-infected and HIV/HCV co-infected patients.

Condition Intervention Phase
Human Immunodeficiency Virus
Hepatitis C

Drug : EBR/GZR
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Impact of HCV Therapy on Cardiovascular Risk and Bone Health

Further study details as provided by Dallas VA Medical Center:

Primary Outcome Measures

  • Evaluate the impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HCV mono-infected patients and HIV/HCV co-infected patients [ Time Frame: 48 weeks ]
    Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, positron emission tomography (PET) scanning for arterial inflammation, coronary calcification and myocardial viability.
Secondary Outcome Measures:
  • Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HCV mono-infected patients. [ Time Frame: Biomarkers of inflammation and bone turnover measured at week 0 of therapy. ]
    Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, PET scanning for arterial inflammation, coronary calcification and myocardial viability. Bone health will be assessed by serological markers of bone turnover and bone mineral density (BMD) by dual energy x-ray absorptiometry (DXA) scan and trabecular bone score (TBS).
  • Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HCV mono-infected patients. [ Time Frame: Bone mineral density measured at week 0 of therapy ]
    Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, PET scanning for arterial inflammation, coronary calcification and myocardial viability. Bone health will be assessed by serological markers of bone turnover and bone mineral density (BMD) by DXA scan and trabecular bone score (TBS).
  • Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HCV mono-infected patients. [ Time Frame: Biomarkers of inflammation and bone turnover measured at week 12 of therapy. ]
    Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, PET scanning for arterial inflammation, coronary calcification and myocardial viability. Bone health will be assessed by serological markers of bone turnover and bone mineral density (BMD) by DXA scan and trabecular bone score (TBS).
  • Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HCV mono-infected patients. [ Time Frame: Biomarkers of inflammation and bone turnover measured at week 24 of therapy. ]
    Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, PET scanning for arterial inflammation, coronary calcification and myocardial viability. Bone health will be assessed by serological markers of bone turnover and bone mineral density (BMD) by DXA scan and trabecular bone score (TBS).
  • Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HCV mono-infected patients. [ Time Frame: Bone mineral density measured at week 48 of therapy. ]
    Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, PET scanning for arterial inflammation, coronary calcification and myocardial viability. Bone health will be assessed by serological markers of bone turnover and bone mineral density (BMD) by DXA scan and trabecular bone score (TBS).
  • Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HIV/HCV co-infected patients. [ Time Frame: Biomarkers of inflammation and bone turnover measured at week 0 of therapy. ]
    Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, PET scanning for arterial inflammation, coronary calcification and myocardial viability. Bone health will be assessed by serological markers of bone turnover and bone mineral density (BMD) by DXA scan and trabecular bone score (TBS).
  • Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HIV/HCV co-infected patients. [ Time Frame: Bone mineral density measured at week 0 of therapy ]
    Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, PET scanning for arterial inflammation, coronary calcification and myocardial viability. Bone health will be assessed by serological markers of bone turnover and bone mineral density (BMD) by DXA scan and trabecular bone score (TBS).
  • Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HIV/HCV co-infected patients. [ Time Frame: Biomarkers of inflammation and bone turnover measured at week 12 of therapy. ]
    Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, PET scanning for arterial inflammation, coronary calcification and myocardial viability. Bone health will be assessed by serological markers of bone turnover and bone mineral density (BMD) by DXA scan and trabecular bone score (TBS).
  • Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HIV/HCV co-infected patients. [ Time Frame: Biomarkers of inflammation and bone turnover measured at week 24 of therapy. ]
    Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, PET scanning for arterial inflammation, coronary calcification and myocardial viability. Bone health will be assessed by serological markers of bone turnover and bone mineral density (BMD) by DXA scan and trabecular bone score (TBS).
  • Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HIV/HCV co-infected patients. [ Time Frame: Biomarkers of inflammation and bone turnover measured at week 48 of therapy. ]
    Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, PET scanning for arterial inflammation, coronary calcification and myocardial viability. Bone health will be assessed by serological markers of bone turnover and bone mineral density (BMD) by DXA scan and trabecular bone score (TBS).

Estimated Enrollment: 60
Study Start Date: August 28, 2017
Estimated Study Completion Date: December 1, 2019
Estimated Primary Completion Date: July 1, 2019 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: EBR/GZR (Zepatier) - HCV/HIV co-infected
Drug: Elbasvir (EBR) 50 mg and Grazoprevir (GZR) 100 mg single tablet by mouth, once daily.
Drug: EBR/GZR

Elbasvir and Grazoprevir (EBR/GZR) tablet by mouth, once daily.

Other Name: Zepatier
Experimental: EBR/GZR (Zepatier) - HCV monoinfected
Drug: Elbasvir (EBR) 50 mg and Grazoprevir (GZR) 100 mg single tablet by mouth, once daily.
Drug: EBR/GZR

Elbasvir and Grazoprevir (EBR/GZR) tablet by mouth, once daily.

Other Name: Zepatier

Detailed Description:

Both HCV and HIV are associated with an increased risk of osteoporosis and osteoporotic fractures among HIV-infected patients and the general population. While HIV significantly increases cardiovascular risk, the contribution of HCV to cardiovascular disease (CVD) is less certain. Increased inflammation could potentially underlie the effect of HCV on CVD, bone health, and other extra-hepatic complications. HCV appears to remain an independent predictor of osteoporotic fractures even after controlling for severity of liver disease. The impact of HCV therapy on inflammation, CVD and bone health is unclear. Our previous studies suggest a beneficial impact of interferon therapy on bone turnover and some CVD markers, while others studies have found on-treatment increases in bone mineral density with interferon-based therapy. Whether these are related to the interferon itself or the virologic response, and whether changes in biomarkers lead to improved fracture risk or CVD morbidity is uncertain. Investigator propose to conduct a prospective analysis of markers of inflammation, immune activation, and bone turnover as well as bone mineral density (BMD) among both HIV/HCV co-infected and HCV mono-infected patients undergoing treatment with the novel direct-acting antiviral elbasvir/grazoprevir (EBR/GZR). Should EBR/GZR therapy significantly improve CV risk and bone health, it would be an additional benefit and indication for its use in HCV therapy.

Eligibility

Eligibility

Ages Eligible for Study: 40 Years and older  
Sexes Eligible for Study: Male  
Accepts Healthy Volunteers: Yes  

Criteria

Inclusion Criteria:

    1. HCV antibody and HCV RNA positive
    2. HCV Genotype 1a, 1b, or 4
    3. Liver staging assessment:

    a. Cirrhosis will be defined by any of the following: i. A liver biopsy prior to day 1 of this study showing cirrhosis (F4) ii. Fibroscan within 12 calendar months of day 1 of this study showing cirrhosis with result > 12.5 kPa iii. FibroSURE performed during screening with a score > 0.75 and APRI > 2 b. Absence of cirrhosis will be defined by any of the following: i. Liver biopsy performed within 24 months of day 1 of this study showing absence of cirrhosis ii. Fibroscan performed within 12 months of day 1 of this study with a result of ≤ 12.5 kPa iii. FibroSURE score ≤ 0.48 and APRI ≤ 1 during screening
  1. If HIV co-infected, HAART regimen will consist of two NRTIs (abacavir, tenofovir disoproxil fumarate or tenofovir alafenamide, each in combination with lamivudine or emtricitabine) with one of the following 3rd agents:
      1. raltegravir
      2. dolutegravir
      3. rilpivirine HIV co-infected patients must be on their stable HAART regimen for at least 6 months, with HIV viral load < 50 c/mL at screening


    Exclusion Criteria:
      1. Hepatitis B surface antigen positivity
      2. Decompensated cirrhosis (Child Pugh B or C)
      3. Any prior hepatitis C treatment
      4. Pregnant or nursing
      5. Treatment with any medication specifically contraindicated with EBR/GZR or not recommended for concomitant use as per the prescribing label (Table 2)
      6. Age less than 18
      7. Prisoners or subjects otherwise involuntarily incarcerated
      8. Absence of signed informed consent by patient or appropriate surrogate
      9. Known hypersensitivity to elbasvir or grazoprevir
      10. For patients with genotype 1a, one more of the following mutations on baseline NS5A
      genotype: M28, Q30, L31, or Y93

    contacts and locations

    Contacts and Locations

    Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

    Please refer to this study by its ClinicalTrials.gov identifier: NCT03221582

    Contacts

    Contact:   Dindi Moore-Matthews, MS 214-857-1415 dindi.moore-matthews@va.gov

    Locations

    United States, Texas
    Dallas VA Medical Center Recruiting
    Dallas, Texas, United States, 75216
    Contact: Dindi Moore-Matthews, MS    214-857-1415    Dindi.Moore-Matthews@va.gov
    Contact: Ashley Liggion-Turk, BS    214-857-1606    Ashley.Liggion-Turk@va.gov
    Principal Investigator: Roger J Bedimo, MD

    Sponsors and Collaborators

    Dallas VA Medical Center
    Merck Sharp & Dohme Corp.

    Investigators

    Principal Investigator: Roger Bedimo, MD Dallas VAMC
    More Information

    More Information


    Responsible Party: Dallas VA Medical Center  
    ClinicalTrials.gov Identifier: NCT03221582   History of Changes  
    Other Study ID Numbers: MISP 54850  
    Study First Received: June 27, 2017  
    Last Updated: March 1, 2018  
    Individual Participant Data    
    Plan to Share IPD: No  

    Studies a U.S. FDA-regulated Drug Product: Yes  
    Studies a U.S. FDA-regulated Device Product: No  

    Additional relevant MeSH terms:
    Hepatitis
    Hepatitis C
    Immunologic Deficiency Syndromes
    Acquired Immunodeficiency Syndrome
    HIV Infections
    Elbasvir-grazoprevir drug combination

    ClinicalTrials.gov processed this data on June 21, 2018
    This information is provided by ClinicalTrials.gov.