Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome

Authors

  • Jose G. Montoya,

    Corresponding author
    1. Department of Medicine, Stanford University School of Medicine, Stanford, California
    2. Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California
    • Correspondence to: Jose G. Montoya, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305.

      E-mail: gilberto@stanford.edu

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  • Andreas M. Kogelnik,

    1. Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California
    Current affiliation:
    1. Open Medicine Institute, Mountain View, CA
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  • Munveer Bhangoo,

    1. Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California
    Current affiliation:
    1. University of California-San Diego School of Medicine, La Jolla, CA
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  • Mitchell R. Lunn,

    1. Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California
    2. Stanford University School of Medicine, Stanford, California
    Current affiliation:
    1. Department of Medicine, Brigham and Women's Hospital, Boston, MA
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    • Harvard Medical School, 25 Shattuck Street, Boston, MA 02115.
  • Louis Flamand,

    1. Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, Laval University, Québec, Canada
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  • Lindsey E. Merrihew,

    1. Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California
    2. Stanford University School of Medicine, Stanford, California
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  • Tessa Watt,

    1. Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California
    Current affiliation:
    1. University of Michigan Medical School, Ann Arbor, MI
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  • Jessica T. Kubo,

    1. Department of Medicine, Stanford University School of Medicine, Stanford, California
    2. Stanford University School of Medicine, Stanford, California
    3. Division of General Medicine Disciplines and Quantitative Sciences Unit, Stanford University School of Medicine, Stanford, California
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  • Jane Paik,

    1. Department of Medicine, Stanford University School of Medicine, Stanford, California
    2. Stanford University School of Medicine, Stanford, California
    3. Division of General Medicine Disciplines and Quantitative Sciences Unit, Stanford University School of Medicine, Stanford, California
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  • Manisha Desai

    1. Department of Medicine, Stanford University School of Medicine, Stanford, California
    2. Stanford University School of Medicine, Stanford, California
    3. Division of General Medicine Disciplines and Quantitative Sciences Unit, Stanford University School of Medicine, Stanford, California
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  • The copyright line for this article was changed on 28 October 2015 after original online publication.

Abstract

There is no known treatment for chronic fatigue syndrome (CFS). Little is known about its pathogenesis. Human herpesvirus 6 (HHV-6) and Epstein–Barr virus (EBV) have been proposed as infectious triggers. Thirty CFS patients with elevated IgG antibody titers against HHV-6 and EBV were randomized 2:1 to receive valganciclovir (VGCV) or placebo for 6 months in a double-blind, placebo-controlled trial. Clinical endpoints aimed at measuring physical and mental fatigue included the Multidimensional Fatigue Inventory (MFI-20) and Fatigue Severity Scale (FSS) scores, self-reported cognitive function, and physician-determined responder status. Biological endpoints included monocyte and neutrophil counts and cytokine levels. VGCV patients experienced a greater improvement by MFI-20 at 9 months from baseline compared to placebo patients but this difference was not statistically significant. However, statistically significant differences in trajectories between groups were observed in MFI-20 mental fatigue subscore (P = 0.039), FSS score (P = 0.006), and cognitive function (P = 0.025). VGCV patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months. Patients in the VGCV arm were 7.4 times more likely to be classified as responders (P = 0.029). In the VGCV arm, monocyte counts decreased (P < 0.001), neutrophil counts increased (P = 0.037) and cytokines were more likely to evolve towards a Th1-profile (P < 0.001). Viral IgG antibody titers did not differ between arms. VGCV may have clinical benefit in a subset of CFS patients independent of placebo effect, possibly mediated by immunomodulation and/or antiviral effect. Further investigation with longer treatment duration and a larger sample size is warranted. J. Med. Virol. 85:2101–2109, 2013. © 2013 The Authors. Journal of Medical Virology Published by Wiley Periodicals, Inc.

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