Antiviral therapy: Valacyclovir Treatment of Alzheimer's Disease (VALAD) Trial: protocol for a randomised, double-blind,placebo-controlled, treatment trial

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dc.contributor.authorDevanand, D. P.
dc.contributor.authorAndrews, Howard
dc.contributor.authorKreisl, William C.
dc.contributor.authorRazlighi, Qolamreza
dc.contributor.authorGershon, Anne
dc.contributor.authorStern, Yaakov
dc.contributor.authorMintz, Akiva
dc.contributor.authorWisniewski, Thomas
dc.contributor.authorAcosta, Edward
dc.contributor.authorPollina, Julianna
dc.contributor.authorKatsikoumbas, Mariasofia
dc.contributor.authorBell, Karen L.
dc.contributor.authorPelton, Gregory H.
dc.contributor.authorDeliyannides, Deborah
dc.contributor.authorPrasad, K. M.
dc.contributor.authorHuey, Edward D.
dc.contributor.otherColumbia University
dc.contributor.otherNew York University
dc.contributor.otherUniversity of Alabama Tuscaloosa
dc.contributor.otherUniversity of Pittsburgh
dc.date.accessioned2023-09-28T19:06:07Z
dc.date.available2023-09-28T19:06:07Z
dc.date.issued2020
dc.description.abstractIntroduction After infection, herpes simplex virus-1 (HSV1) becomes latent in the trigeminal ganglion and can enter the brain via retrograde axonal transport. Recurrent reactivation of HSV1 may lead to neurodegeneration and Alzheimer's disease (AD) pathology. HSV1 (oral herpes) and HSV2 (genital herpes) can trigger amyloid beta-protein (A beta) aggregation and HSV1 DNA is common in amyloid plaques. Anti-HSV drugs reduce A beta and phosphorylated tau accumulation in cell-culture models. Cognitive impairment is greater in patients with HSV seropositive, and antiviral drugs show robust efficacy against peripheral HSV infection. Recent studies of electronic health records databases demonstrate that HSV infections increase dementia risk, and that antiviral medication treatment reduces this risk. The generic antiviral drug valacyclovir was superior to placebo in improving memory in a schizophrenia pilot trial but has not been tested in AD. Methods and analysis In patients with mild AD who test positive for HSV1 or HSV2 serum antibodies, valacyclovir, repurposed as an anti-AD drug, will be compared with placebo (lactose pills) in 130 patients (65 valacyclovir and 65 placebo) in a randomised, double-blind, 78-week phase II proof-of-concept trial. Patients on valacyclovir, dose-titrated from 2 g to a targeted oral dose of 4 g daily, compared with placebo, are hypothesised to show smaller cognitive and functional decline, and, using F-18-Florbetapir positron emission tomography (PET) and F-18-MK-6240 PET imaging, to show less amyloid and tau accumulation, respectively. In the lumbar puncture subsample, cerebrospinal fluid acyclovir will be assayed to assess central nervous system valacyclovir penetration. Ethics and dissemination The trial is being overseen by the New York State Psychiatric Institute Institutional Review Board (protocol 7537), the National Institute on Ageing, and the Data Safety Monitoring Board. Written informed consent is obtained for all subjects. Results will be disseminated via publication, clinicaltrials.gov, media and conferences.en_US
dc.format.mediumelectronic
dc.format.mimetypeapplication/pdf
dc.identifier.citationDevanand, D. P., Andrews, H., Kreisl, W. C., Razlighi, Q., Gershon, A., Stern, Y., Mintz, A., Wisniewski, T., Acosta, E., Pollina, J., Katsikoumbas, M., Bell, K. L., Pelton, G. H., Deliyannides, D., Prasad, K. M., & Huey, E. D. (2020). Antiviral therapy: Valacyclovir Treatment of Alzheimer’s Disease (VALAD) Trial: protocol for a randomised, double-blind,placebo-controlled, treatment trial. In BMJ Open (Vol. 10, Issue 2, p. e032112). BMJ. https://doi.org/10.1136/bmjopen-2019-032112
dc.identifier.doi10.1136/bmjopen-2019-032112
dc.identifier.orcidhttps://orcid.org/0000-0002-3379-8966
dc.identifier.orcidhttps://orcid.org/0000-0002-6234-4517
dc.identifier.urihttps://ir.ua.edu/handle/123456789/10861
dc.languageEnglish
dc.language.isoen_US
dc.publisherBMJ
dc.rights.licenseAttribution-NonCommercial 4.0 International (CC BY-NC 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.subjectSIMPLEX-VIRUS TYPE-1
dc.subjectNEUROTROPIC HERPES VIRUSES
dc.subjectMILD COGNITIVE IMPAIRMENT
dc.subjectAPOLIPOPROTEIN-E
dc.subjectDOUBLE-BLIND
dc.subjectBRAIN
dc.subjectINFECTION
dc.subjectRISK
dc.subjectASSOCIATION
dc.subjectDEMENTIA
dc.subjectMedicine, General & Internal
dc.titleAntiviral therapy: Valacyclovir Treatment of Alzheimer's Disease (VALAD) Trial: protocol for a randomised, double-blind,placebo-controlled, treatment trialen_US
dc.typeArticle
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