Anti Viral Treatment in Mild Cognitive Impairment

Plain English Summary

Valacyclovir for Mild Cognitive Impairment is a Phase 2 clinical trial sponsored by New York State Psychiatric Institute studying Mild Cognitive Impairment, Herpes Simplex 1, Herpes Simplex 2. This study investigates if an antiviral medication, valacyclovir, can help people with early signs of memory loss (Mild Cognitive Impairment or MCI). It is designed for individuals aged 50-95 who have been diagnosed with MCI and have evidence of Alzheimer's disease biomarkers. Participants will take either the antiviral drug or a placebo for 52 weeks, with regular check-ups. There are no direct alternatives to this specific antiviral treatment for MCI, but other approaches may focus on managing symptoms or slowing progression. The trial aims to enroll 50 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are between 50 and 95 years old and have been diagnosed with MCI. You must have a positive test for antibodies to common viruses (HSV1 or HSV2) and show signs of Alzheimer's disease through a brain scan or spinal fluid test. You cannot join if you have current major mental health conditions like schizophrenia or severe depression, or a history of substance abuse. Certain medical conditions like severe kidney problems, uncontrolled high blood pressure, or recent stroke may also prevent participation. This trial is studying Mild Cognitive Impairment, Herpes Simplex 1, Herpes Simplex 2, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how the antiviral drug affects the buildup of a protein (amyloid) in the brain over a year, which is a key indicator in Alzheimer's disease progression. The specific primary outcome measures are: Change in Standardized Uptake Value Ratio (SUVR) of (18F-Florbetapir PET) From Week 0 to Week 52. (Week 0 to Week 52). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial is important because it explores a new approach to potentially treat Mild Cognitive Impairment by targeting a suspected viral cause of Alzheimer's disease, addressing a gap in current treat Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Mild Cognitive Impairment, Herpes Simplex 1, Herpes Simplex 2, where improved treatment options are needed.

Investor Insight

This Phase II trial, testing a repurposed antiviral drug for MCI, signals potential for a novel treatment in the large and growing Alzheimer's disease market, with a moderate probability of success gi Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this trial is right for you, especially regarding your MCI diagnosis and any viral infections. Be prepared for regular visits over a year, which will include cognitive tests, blood work, and possibly brain imaging. You will need to take study medication daily and report any side effects or other medications you are taking. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: TRIPLE
• Enrollment: 50 participants

Interventions

• DRUG: Valacyclovir hydrochloride 500mg caplet — Active Comparator
• DRUG: Placebo sugar pill caplet — Placebo Comparator

Primary Outcomes

• Change in Standardized Uptake Value Ratio (SUVR) of (18F-Florbetapir PET) From Week 0 to Week 52. (Week 0 to Week 52)

Secondary Outcomes

• Change From Week 0 to Week 52 in the Alzheimer's Disease Cooperative Study-Preclinical Alzheimer Cognitive Composite (PACC) Z-score (Assessed by Change in Least Square Means from Week 0 to Week 52 (measure in Outcome Measure Data Table), covarying for baseline score, age, sex and apolipoprotein E e4 status.)
• Change From Week 0 to Week 52 in the Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale-Prevention Instrument (ADCS-ADL-PI) (Assessed by Change in Least Square Means from Week 0 to Week 52 (measure in Outcome Measure Data Table), covarying for baseline score, age, sex and apolipoprotein E e4 status.)
• Change From Week 0 to Week 52 in Clinical Dementia Rating (CDR) Sum of Boxes (Assessed by Change in Least Square Means from Week 0 to Week 52 (measure in Outcome Measure Data Table), covarying for baseline score, age, sex and apolipoprotein E e4 status.)

Full Eligibility 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 or memantine is not required but will be permitted. If already prescribed, doses of these medications must be stable for 1 month prior to study entry. Patients are permitted to receive cholinesterase inhibitors and/or memantine throughout the duration of the study. Any changes to the medication will be documented in the participant research chart. Medications given for other medical reasons, e.g., antidiabetic 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. Details of concomitant medication use will be documented at all visits and will be available for statistical analysis.(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. (SRMP Assessment by Study Physician)
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 thyroid stimulating hormone (TSH) levels above 4.94 mlU/L. (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)

Trial Locations

• New York State Psychiatric Institute, New York, New York, United States

Frequently Asked Questions

Related Conditions

• Mild Cognitive Impairment
• Alzheimer's Disease
• Dementia
• Herpes Simplex Virus
• Viral Infections
• Neurodegenerative Diseases
• Cognitive Disorders
• Memory Loss
• Geriatrics
• Neurology

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