Valacyclovir for Mild Cognitive Impairment (VALMCI)
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|ClinicalTrials.gov Identifier: NCT04710030|
Recruitment Status : Not yet recruiting
First Posted : January 14, 2021
Last Update Posted : January 19, 2021
|Condition or disease||Intervention/treatment||Phase|
|Mild Cognitive Impairment Herpes Simplex 1 Herpes Simplex 2||Drug: Valacyclovir hydrochloride 500g caplet Drug: Placebo sugar pill caplet||Phase 2|
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.This trial will intervene at an earlier stage (MCI).
In AD biomarker positive patients with Mild Cognitive Impairment (eMCI and lMCI) who test positive for serum antibodies to HSV1 or HSV2, the generic antiviral drug valacyclovir will be compared at oral doses of 4 grams per day, to matching placebo in the treatment of 50 patients (25 valacyclovir, 25 placebo) in a randomized, double-blind, 52-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 52-week trial.
We will explore apolipoprotein E e4 genotype as a moderator, and changes in global clinical status, viral antibodies and proteomic assays, AD signature of MRI regional and whole brain cortical thinning, and plasma total tau, p-tau epitopes and neurofilament light (Nfl) protein markers for neurodegeneration as exploratory hypotheses.
This innovative Phase II proof of concept trial clearly has exceptionally high reward potential for the treatment of MCI.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Masking Description:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||Anti Viral Treatment in Mild Cognitive Impairment|
|Estimated Study Start Date :||February 1, 2021|
|Estimated Primary Completion Date :||February 1, 2023|
|Estimated Study Completion Date :||December 31, 2023|
Active Comparator: Valacyclovir
Oral valacyclovir will be distributed in 500mg caplets. Patients will take 8 caplets per day (total dose: 4 grams per day) for 52 weeks.
Drug: Valacyclovir hydrochloride 500g caplet
Other Name: Valtrex
Placebo Comparator: Placebo
The oral placebo (sugar pill) will be distributed in 500mg caplets. Patients will take 8 caplets per day for 52 weeks.
Drug: Placebo sugar pill caplet
Other Name: Placebo
- Change in accumulation of amyloid plaque (18F-Florbetapir PET) from Screening or Week 0 to Week 52. [ Time Frame: Screening or Week 0 and Week 52 ]18F-Florbetapir PET imaging will show amyloid accumulation in sum of six ROIs (cerebellar reference) that show increased uptake in AD: medial orbital frontal, anterior cingulate, parietal, temporal, posterior cingulate, precuneus.
- Change in Alzheimer's Disease Cooperative Study- Preclinical Alzheimer Cognitive Composite (PAAC) cognitive composite score from Week 0 to Week 52. [ Time Frame: Week 0, week 12, week 26, Week 52 ]The ADCS-PACC combines four widely used paper-and-pencil cognitive tests. These include the list- learning task from the Free and Cued Selective Reminding Test (FCSRT), as well as a paragraph- recall test from the Wechsler Memory Scale, both of which measure episodic memory. The Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale tests executive function. The final component, the Mini-Mental State Examination (MMSE), assesses global functioning and mental status. Scores range from -5 to +5 with higher scores indicating less deficit and lower scores indicating greater deficit.
- Change in Alzheimer's Disease Cooperative Study-Activities of Daily Living scale-PI (ADCS-ADL-PI) score from Week 0 to Week 52. [ Time Frame: Week 0, week 12, week 26, Week 52 ]The ADCS-ADL-PI will be administered to the patient, for the assessment of impairments of complex Activities of Daily Living for patients with MCI. Scores range from 18-54 with higher scores indicating greater deficit and lower scores indicating less deficit.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04710030
|Contact: Davangere Devanand, MDfirstname.lastname@example.org|
|Contact: Lauren Tursi, BAemail@example.com|
|United States, New York|
|New York State Psychiatric Institute|
|New York, New York, United States, 10032|
|Contact: Julianna Pollina, BS 646-774-8638 Julianna.Pollina@nyspi.columbia.edu|
|Principal Investigator: Davangere Devanand, MD|
|Sub-Investigator: Terry Goldberg, Ph.D|
|Principal Investigator:||Davangere Devanand, MD||Columbia University Irving Medical Center|