Can Valacyclovir Attenuate Inflammation in Antiretroviral-Treated HIV-Infected Individuals With Herpes Simplex Virus Type 2? (VALIANT Pilot)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2010 by University Health Network, Toronto.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
University of Toronto
Canadian Institutes of Health Research (CIHR)
Information provided by:
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01176409
First received: August 4, 2010
Last updated: December 22, 2010
Last verified: December 2010
  Purpose

The purpose of this study is to compare the levels of immune and inflammatory markers among HIV-1, HSV-2 co-infected adults achieving plasma HIV RNA suppression to <50 copies/mL, between those randomized to valacyclovir and placebo, over a twelve-week intervention period.


Condition Intervention Phase
HIV Infections
Herpes Simplex
Drug: Valacyclovir
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: VALacyclovir for Inflammation AttenuatioN Trial Pilot (VALIANT Pilot)

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Percentage activated CD8+ T-cells [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Percentage of CD8+ T-cells co-expressing CD38 and HLA-DR


Secondary Outcome Measures:
  • Inflammatory markers [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    IL-6, hsCRP, sICAM-1, LPS

  • CD4 cell count [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    CD4 cell count (absolute and percentage)

  • Virologic blips [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Plasma HIV RNA level >50 copies/mL but <1000 copies/mL, followed by a repeat plasma HIV RNA level <50 copies/mL.

  • Drug-related adverse events [ Time Frame: 18 weeks ] [ Designated as safety issue: Yes ]
    Adverse events (AEs) are defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study medication. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not it is related to the medication.

  • HSV reactivations [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Clinical reactivations of herpes simplex virus. Simultaneous reactivations at more than one anatomic site will be counted as a single reactivation event.

  • Acyclovir-resistant HSV [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
    Clinical reactivations of herpes simplex virus that are microbiologically confirmed to be caused by acyclovir-resistant virus.


Estimated Enrollment: 60
Study Start Date: September 2010
Estimated Study Completion Date: September 2011
Estimated Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High dose valacyclovir
Valacyclovir 1g po BID
Drug: Valacyclovir
Valacyclovir will be used at two different dosages (1g po BID and 500mg po BID) to be used for 12 weeks. Supplied as 500mg caplets.
Other Names:
  • Apo-Valacycyclovir
  • Valtrex
Active Comparator: Low dose valacyclovir
Valacyclovir 500mg po BID
Drug: Valacyclovir
Valacyclovir will be used at two different dosages (1g po BID and 500mg po BID) to be used for 12 weeks. Supplied as 500mg caplets.
Other Names:
  • Apo-Valacycyclovir
  • Valtrex
Placebo Comparator: Placebo
Inert placebo
Drug: Placebo
Placebo, supplied as caplets identical in appearance, odour and taste to valacyclovir 500mg caplets.

Detailed Description:

Highly active antiretroviral therapy (HAART) has dramatically reduced HIV-1 infection (herein referred to as 'HIV') related morbidity and mortality, transforming an invariably fatal disease into a manageable, chronic condition. Yet even HAART-treated HIV infection is characterized by chronic systemic inflammation and immune activation. This systemic inflammatory response is composed of multiple components, and can be quantified by measuring markers of immune activation, inflammatory cytokines, acute phase reactants, endothelial activation markers, and markers of microbial translocation. This inflammation is clinically relevant, as it may contribute directly to HIV disease progression and non-AIDS related morbidity and mortality in HIV-infected patients. Because this inflammation persists even in the context of suppressive HAART, albeit at modestly decreased levels, adjunctive therapeutic strategies to attenuate this persistent inflammatory response are therefore needed. Herpes simplex virus type 2 is a common, clinically important co-infection seen in individuals living with HIV infection, and may contribute to this ongoing inflammation. This pilot trial will investigate whether short-term valacyclovir for HSV-2 suppression can decrease systemic inflammation in HAART-treated, HIV-1, HSV-2 co-infected individuals.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult (aged 18 years or older)
  • documented HIV-1 infection (determined by EIA and Western blot)
  • documented HSV-2 seropositivity (determined by ELISA during screening)
  • no use of chronic anti-HSV therapy for the past 6 months, and not anticipated to require chronic anti-HSV therapy during the study
  • sustained plasma HIV RNA<50 copies/mL on HAART for at least 12 months
  • no active opportunistic infection for at least 12 months

Exclusion Criteria:

  • hepatitis C co-infection
  • hepatitis B co-infection
  • pregnancy or actively planning to become pregnant
  • receiving chemotherapy, chronic steroid therapy or other immunomodulatory medications (e.g. interferon, azathioprine, methotrexate, TNF-alpha antagonists, etc.)
  • Estimated creatinine clearance <30 mL/min
  • Other medical condition likely to cause death within 24 months
  • Enrolled in any other interventional clinical trial
  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: NCT01176409

Contacts
Contact: Darrell H.S. Tan, MD FRCPC 416-340-5077 darrell.tan@gmail.com
Contact: Sharon L Walmsley, MD FRCPC MSc 416-340-3871

Locations
Canada, Ontario
Toronto General Hospital, University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2N2
Contact: Warmond Chan    416-340-4800 ext 6954    warmond.chan@uhn.on.ca   
Sub-Investigator: Darrell H.S. Tan, MD FRCPC MSc         
Principal Investigator: Sharon L Walmsley, MD FRCPC MSc         
Sponsors and Collaborators
University Health Network, Toronto
University of Toronto
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: Darrell H.S. Tan, MD FRCPC University Health Network, University of Toronto
Principal Investigator: Sharon L Walmsley, MD FRCPC MSc University Health Network, University of Toronto
  More Information

Additional Information:
No publications provided by University Health Network, Toronto

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sharon Walmsley, University Health Network
ClinicalTrials.gov Identifier: NCT01176409     History of Changes
Other Study ID Numbers: VALIANT-001
Study First Received: August 4, 2010
Last Updated: December 22, 2010
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Inflammation
Herpes Simplex
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Pathologic Processes
Herpesviridae Infections
DNA Virus Infections
Skin Diseases, Viral
Skin Diseases, Infectious
Skin Diseases
Valacyclovir
Acyclovir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014