https://clinicaltrials.gov/ct2/show/NCT03282916

Anti-viral Therapy in Alzheimer’s Disease

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ClinicalTrials.gov Identifier: NCT03282916

Recruitment Status : Recruiting

First Posted : September 14, 2017
Last Update Posted : January 25, 2019
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Davangere P. Devanand, New York State Psychiatric Institute
Study Description
Brief Summary:
Anti-viral therapy in Alzheimer’s disease will investigate the efficacy of treating patients with mild Alzheimer’s disease with the U.S.A marketed generic anti-viral drug Valtrex (valacyclovir, 500mg oral tablet). Valacyclovir at 2 g to 4 g per day, repurposed to treat Alzheimer’s disease, will be compared to matching placebo in the treatment of 130 mild AD patients (65 valacyclovir, 65 placebo) who test positive for herpes simplex virus-1 (HSV1) or HSV2. The study will be a randomized, double-blind, 18-month Phase II proof of concept trial.
Condition or disease Intervention/treatment Phase
Alzheimer DiseaseHerpes Simplex 1Herpes Simplex 2 Drug: ValacyclovirDrug: Placebo Phase 2
Detailed Description:

Many viruses are latent for decades before being reactivated in the brain by stress, immune compromise, or other factors. After the initial oral infection, herpes simplex virus-1 (HSV1) becomes latent in the trigeminal ganglion and can later enter the brain via retrograde axonal transport, often targeting the temporal lobes.

HSV1 can also enter the brain via olfactory neurons directly. HSV1 (oral herpes) and HSV2 (genital herpes) are known to trigger amyloid aggregation and their DNA is commonly found in amyloid plaques. Anti-HSV drugs reduce Aβ and p-tau accumulation in brains of infected mice. HSV1 reactivation is associated with tau hyperphosphorylation in mice and may play a role in tau propagation across neurons. In humans, recurrent reactivation with newly produced HSV1 particles, ‘drop by drop,’ may produce neuronal damage and eventually lead to neurodegeneration and Alzheimer’s disease (AD) pathology, partly due to effects on amyloid and tau. Clinical studies show cognitive impairment in HSV seropositive patients in different patient groups and in healthy adults, and antiviral treatments show robust efficacy against peripheral HSV infection. The study team will conduct the first-ever clinical trial to directly address the long-standing viral etiology hypothesis of AD which posits that viruses, particularly the very common HSV1 and HSV2, may be etiologic or contribute to the pathology of AD.

In patients with mild AD who test positive for serum antibodies to HSV1 or HSV2, the generic antiviral drug valacyclovir, repurposed as an anti-AD drug, will be compared at oral doses of 2 to 4 grams per day to matching placebo in the treatment of 130 patients (65 valacyclovir, 65 placebo) in a randomized, double-blind, 78-week Phase II proof of concept trial. Patients treated with valacyclovir are hypothesized to show smaller decline in cognition and functioning compared to placebo, and, using 18F-Florbetapir PET imaging, to show less amyloid accumulation than placebo over the 78-week trial. Through the use of tau PET imaging with the tracer 18F-MK-6240 at baseline and 78 weeks, patients treated with valacyclovir are hypothesized to show smaller increases in 18F-MK-6240 binding than patients treated with placebo from baseline to 78 weeks. Apolipoprotein E genotype at baseline, as well as changes in cortical thinning on structural MRI, olfactory identification deficits, and antiviral antibody titers from baseline to 78 weeks, will be evaluated in exploratory analyses. In patients who agree to lumbar puncture, plasma and CSF acyclovir will be assayed to establish the degree of CNS penetration of valacyclovir in mild AD, and the investigators will obtain CSF Aβ42, tau, p-tau for subset exploratory analyses with changes in outcome measures.

If this trial is successful, the investigators will apply for funding to conduct a larger, multicenter, Phase III study using a study design that will be informed by the results of this Phase II trial. This innovative Phase II proof of concept trial clearly has exceptionally high reward potential for the treatment of AD.

Study Design
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Anti-viral Therapy in Alzheimer’s Disease
Actual Study Start Date : February 12, 2018
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2022
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**Comment**
Remember, Alzheimer’s is a label, nothing more.  They are still trying to figure out what causes it.
Dr. Klinghardt has gone on record stating that he’s not had one MS, ALS, or Parkinson’s patient NOT test positive for Lyme:  https://madisonarealymesupportgroup.com/2019/01/23/never-had-a-single-ms-als-or-parkinsons-patient-in-past-5-years-who-didnt-test-positive-for-lyme-dr-klinghardt/