Impact of Hepatitis C Therapy and Bone Health (HCV)

August 15, 2019 updated by: Dallas VA Medical Center

Impact of HCV Therapy on Cardiovascular Risk and Bone Health

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
6

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 75216
        • Dallas VA Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

  4. 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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 Names:
  • Zepatier

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
48 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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).
Biomarkers of inflammation and bone turnover measured at week 0 of therapy.
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).
Bone mineral density measured at week 0 of therapy
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).
Biomarkers of inflammation and bone turnover measured at week 12 of therapy.
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).
Biomarkers of inflammation and bone turnover measured at week 24 of therapy.
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).
Bone mineral density measured at week 48 of therapy.
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).
Biomarkers of inflammation and bone turnover measured at week 0 of therapy.
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).
Bone mineral density measured at week 0 of therapy
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).
Biomarkers of inflammation and bone turnover measured at week 12 of therapy.
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).
Biomarkers of inflammation and bone turnover measured at week 24 of therapy.
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).
Biomarkers of inflammation and bone turnover measured at week 48 of therapy.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Dallas VA Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Merck Sharp & Dohme LLC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Roger Bedimo, MD, Dallas VAMC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 28, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 26, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 30, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 27, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 13, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 18, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 19, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 15, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MISP 54850

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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