title: Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome.
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.
authors: Department of Medicine, Stanford University School of Medicine, Stanford, California; Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California.
authors: Jose G
authors: JG
authors: Montoya
authors: Andreas M
authors: AM
authors: Kogelnik
authors: Munveer
authors: M
authors: Bhangoo
authors: Mitchell R
authors: MR
authors: Lunn
authors: Louis
authors: L
authors: Flamand
authors: Lindsey E
authors: LE
authors: Merrihew
authors: Tessa
authors: T
authors: Watt
authors: Jessica T
authors: JT
authors: Kubo
authors: Jane
authors: J
authors: Paik
authors: Manisha
authors: M
authors: Desai
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D015673:Fatigue Syndrome, Chronic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004854:Herpesvirus 4, Human / Q000276:immunology; D015654:Herpesvirus 6, Human / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D009504:Neutrophils; D012307:Risk Factors; D016896:Treatment Outcome; D000077562:Valganciclovir
chemical_list: D000914:Antibodies, Viral; D000998:Antiviral Agents; D016207:Cytokines; D007074:Immunoglobulin G; D000077562:Valganciclovir; D015774:Ganciclovir
keywords: Epstein-Barr virus; chronic fatigue syndrome; human herpesvirus 6; randomized clinical trial; valganciclovir