Valacyclovir for Mild Cognitive Impairment

• Status: Recruiting
• Trial end date: 2023-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Anti-viral treatment in Mild Cognitive Impairment (MCI) is a Phase II, placebo-controlled, 52-week trial using oral valacyclovir 4 g/day in 50 HSV seropositive, AD biomarker-positive, amnestic mild cognitive impairment (MCI) patients (eMCI and lMCI). The trial will directly address the long-standing viral etiology hypothesis of Alzheimer's disease (AD) which posits that viruses, particularly the very common herpes simplex virus-1 (HSV1) and herpes simplex virus-2 (HSV2), may be etiologic or contribute to the pathology of AD. This trial will intervene at an earlier stage (MCI). We will compare the repurposed drug valacyclovir to placebo in patients with amnestic MCI (eMCI and lMCI) in a randomized, double-blind, two-arm parallel group 52-week pilot trial. Our Phase II trial will be the first antiviral drug trial conducted in MCI.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: New York State Psychiatric Institute
• Collaborator: Alzheimer's Association
• Treatments: Valacyclovir

Criteria

Inclusion Criteria:

1. Males and females ages 50-95. Females must be postmenopausal, defined as 12 consecutive months without menstruation. (Patient Report)

2. Diagnosis of MCI (includes eMCI and lMCI by ADNI criteria)(Neuropsychological Evaluation)

3. Folstein Mini Mental State (MMSE) greater than or equal to 23/30. (Neuropsychological Evaluation)

4. Patient retains capacity to consent for him/herself. (Physician Evaluation)

5. At screening, patients must test positive for serum antibodies to HSV1 or HSV2. (Laboratory Tests)

6. Use of cholinesterase inhibitors and memantine. Doses of these medications will need to be stable for at least 1 month prior to study entry. Any changes to the medication will be documented in the participant research chart. Medications given for other medical reasons, e.g., anti-diabetic or anti-hypertensive medications, will not be altered for the purposes of this trial and the patient's primary physician may adjust such medications as medically indicated throughout the trial. (Patient Report)

7. Either PET amyloid scan positivity at screening, or prior CSF biomarker positive for AD. (Medical Records or through completing a PET scan as part of screening)

Exclusion Criteria:

1. Current clinical diagnosis of schizophrenia, schizoaffective disorder, other psychosis, bipolar disorder or current major depression by DSM-5 criteria. Prior history of major depression will not be exclusionary. (Physician Evaluation)

2. Active suicidal intent or plan based on clinical assessment. (Physician Evaluation)

3. Current or recent (past 6 months) alcohol or substance use disorder (DSM-5 criteria). (Physician Evaluation)

4. Current diagnosis of other major neurological disorders, including Parkinson's disease, multiple sclerosis,CNS infection, Huntington's disease, and amyotrophic lateral sclerosis. (Physician Evaluation)

5. Clinical stroke with residual clinical deficits. MRI findings of cerebrovascular disease (small infarcts, lacunes, periventricular disease) in the absence of clinical stroke with residual neurological deficits will not lead to exclusion. (Physician Evaluation)

6. Acute, severe, unstable medical illness. For cancer, patients with active illness or metastases in the last 12 months will be excluded, but past history of successfully treated cancer will not lead to exclusion. (Physician Evaluation)

7. Sitting blood pressure > 160/100 mm Hg. (Physician Evaluation)

8. Renal failure as determined by an estimated Glomerular Filtration Rate (GFR) < 44 ml/min/1.73m2. (Laboratory Report)

9. Serum vitamin B12 levels below the normal range. (Laboratory Report)

10. Patients with abnormal TFTs. (Laboratory Report)

11. Use of benzodiazepines in lorazepam equivalent doses equal to or greater than 2 mg daily. (Patient Report)

12. For MRI, metal implants and pacemaker, and claustrophobia such that the patient refuses MRI. (Patient Report)

13. Radiation exposure in the prior 12 months that, together with 18F- Florbetapir will be above the FDA annual radiation exposure threshold. (Patient Report and Physician Evaluation)

14. Severe vision or hearing impairment that would prevent the participant from performing the psychometric tests accurately. This will be a clinical determination by the study physician without formal testing or audiometry.(Physician Evaluation)