Summary

for people ages 18 years and up (full criteria)
at San Diego, California
study started
estimated completion:
Ajay Bharti

Description

Summary

This partially blinded placebo-controlled trial will determine the impact of curing Hepatitis C Virus (HCV) with an oral direct-acting antiviral (DAA), ledipasvir and sofosbuvir in a single pill, on central nervous system (CNS) outcomes in mono- or Human Immunodeficiency Virus (HIV) co-infected individuals.

Details

Chronic HCV infection frequently causes neurocognitive (NC) and mood disorders but whether these disorders are caused by HCV or by the concomitant substance use and liver disease is unclear. Response to treatment has been obscured by the neurotoxicity of interferon-based HCV therapies. Newer DAAs are not neurotoxic and are expected to treat HCV-induced brain injury. However, clinical trials have yet to be performed to determine their CNS benefits. This presents a critical barrier to progress in the field that the proposed clinical trial will directly address. The specific aims will be to:

AIM 1: To determine whether curing HCV, as indexed by 12-week sustained virologic response, results in improvement in NC performance, neuroimaging, and measures of daily functioning;

AIM 2: To determine the viral, host, and pharmacologic correlates of neurocognitive and neuroimaging outcomes; and

AIM 3: To explore how HIV alters the relationships observed in Aims 1 and 2.

The proposed, innovative clinical trial will improve scientific knowledge by determining the biological and imaging correlates of the CNS and systemic effects of DAAs as well as the distribution of these drugs into the CNS. The investigators' findings will also inform clinical guidelines and practice about the safety and benefits of treating HCV in substance using populations. In people who have HIV-associated NC disorder and HCV infection, treatment with DAAs may prove to be a critical adjunct to antiretroviral for improving cognition and returning patients to more functional lives.

Keywords

Hepatitis C Human Immunodeficiency Virus Hepatitis Hepatitis A Immunologic Deficiency Syndromes Acquired Immunodeficiency Syndrome HIV Infections Sofosbuvir Ledipasvir Ledipasvir, sofosbuvir drug combination ledipasvir and sofosbuvir Immediate (IMM) Delayed (DEL)

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Adult (≥ 18 years old) subjects with chronic genotype 1 HCV and NCI with a GDS greater than or equal to 0.5 (n=60).
  2. Presence of chronic HCV infection based on chart review will be defined as positive for anti-HCV antibody or HCV RNA at least 6 months before screening.
  3. For the HIV/HCV co-infected group only, subjects must have HIV. HIV status will be obtained through self report. Self report will be confirmed at screening using a HIV-1 point of care test. In the event that point of care test and self-report are discordant, then HIV status will be confirmed by a licensed Western blot or a second antibody test.
  4. HIV/HCV co-infected subjects (n=12) must also have a HIV RNA measurement <50 copies/mL at the pre-treatment visit.
  5. Laboratory values:
  6. Platelets >150,000
  7. Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) <10x upper limit of normal
  8. Creatinine clearance >30 milliliters/minute/1.73 centimeter squared

You CAN'T join if...

  1. Ledipasvir (LDV)/Sofosbuvir (SOF) is known to have drug interactions if co-administered with the following drugs:
  2. Amiodarone
  3. P-glycoprotein (P-gp) inducers (e.g., rifampin, St. John's wort)
  4. Cirrhosis or bridging fibrosis (Modified hepatic activity index (mHAI) stages 4-6 or its equivalent).
  5. Liver biopsy at any time showing mHAI stage 4 or higher fibrosis OR
  6. FibroScan within 12 months demonstrating liver stiffness of ≥9.5 kilo Pascal or
  7. AST to platelet ratio index (APRI) ≥2.0 and Fibrosis-4 (FIB-4) ≥3.25
  8. NOTE: If APRI and FIB-4 are discordant one of the other forms of fibrosis staging must be used.
  9. Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.
  10. Any cause of liver disease other than chronic HCV infection, including but not limited to the following:
  11. Hemochromatosis
  12. Alpha-1 antitrypsin deficiency
  13. Wilson's disease
  14. Autoimmune hepatitis
  15. Alcoholic liver disease
  16. Drug-related liver disease
  17. Severe NC confounding conditions (stroke, head injury, or developmental learning disability).
  18. Regular use of anti-inflammatory drugs.
  19. Current or recent treatment with pegylated interferon (PEG-IFN).
  20. Other active inflammatory process (major infection, malignancy, rheumatoid arthritis/autoimmune disorder) within the prior 28 days.
  21. Contraindications to magnetic resonance imaging (MRI).
  22. . Bleeding diathesis, thrombocytopenia, or use of anticoagulants that would contraindicate lumbar puncture.
  23. . Uncontrolled or active depression or other psychiatric disorder that in the opinion of the site investigator might preclude adherence to study requirements or impact NC functioning and assessments.
  24. . Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  25. . Presence of active or acute AIDS-defining opportunistic infections within 12 weeks prior to study entry.

Location

  • Ucsd Hnrp accepting new patients
    San Diego California 92103 United States

Lead Scientist

  • Ajay Bharti
    Associate Clinical Professor, Medicine. Authored (or co-authored) 15 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Diego
ID
NCT02650024
Phase
Phase 4
Study Type
Interventional
Last Updated