Valacyclovir for Mild Cognitive Impairment

(VALMCI Trial)

Overseen By Cileyn Herrera, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: New York State Psychiatric Institute

Must not be taking: Benzodiazepines

Disqualifiers: Schizophrenia, Bipolar, Major depression, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether the antiviral drug valacyclovir can slow the progression of mild cognitive impairment (MCI), a condition that might lead to Alzheimer's disease. Researchers are testing the hypothesis that viruses, such as the common herpes simplex virus (HSV), could contribute to Alzheimer's. They seek to discover if treating the virus with valacyclovir makes a difference. Participants will take either valacyclovir or a placebo (a sugar pill) for 52 weeks. The trial seeks individuals diagnosed with mild cognitive impairment who have tested positive for herpes simplex virus antibodies. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

You can continue taking your current medications, including cholinesterase inhibitors or memantine, as long as the doses are stable for 1 month before starting the trial. Other medications for conditions like diabetes or high blood pressure can also be adjusted by your primary doctor during the trial.

Is there any evidence suggesting that valacyclovir is likely to be safe for humans?

Research shows that valacyclovir is generally safe for use. In earlier studies, patients with early-stage Alzheimer's who took high doses of valacyclovir found it safe and manageable over a four-week period. This finding is encouraging for its potential use in mild cognitive impairment (MCI).

However, some rare side effects have been reported. In very rare cases, valacyclovir has been linked to mental effects like psychosis, a condition where a person loses touch with reality. Despite this, such effects are uncommon.

Overall, valacyclovir is widely used to treat viral infections and has a strong safety record. As with any treatment, monitoring for unusual symptoms is important. Prospective trial participants should discuss any concerns with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for mild cognitive impairment, which often focus on managing symptoms with medications like cholinesterase inhibitors, valacyclovir offers a fresh approach by targeting viral infections that may contribute to cognitive decline. Valacyclovir is an antiviral medication traditionally used for herpes infections, and researchers are intrigued by its potential to address underlying viral factors in cognitive impairment. This novel mechanism, addressing a possible root cause rather than just symptoms, is what makes valacyclovir a promising candidate in the quest for more effective cognitive treatments.

What evidence suggests that valacyclovir might be an effective treatment for mild cognitive impairment?

Research is exploring whether valacyclovir, a medication that fights viruses, can aid individuals with mild cognitive impairment (MCI), a condition affecting memory and thinking. This interest stems from the idea that certain viruses, like the herpes simplex virus (HSV), might be linked to Alzheimer's disease. Studies have shown that high doses of valacyclovir are safe for individuals in the early stages of Alzheimer's. However, past trials have not consistently demonstrated clear long-term improvements in memory and thinking for Alzheimer's patients. In this trial, participants will receive either valacyclovir or a placebo. The researchers hope that using valacyclovir earlier, during MCI, might slow the progression of memory and thinking problems. ^{1 2 3 4 6}

Who Is on the Research Team?

Davangere Devanand, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for people aged 50-95 with Mild Cognitive Impairment who test positive for herpes simplex virus, have certain Alzheimer's disease biomarkers, and can consent for themselves. Women must be postmenopausal. Participants may use some memory medications if doses are stable. Exclusions include major neurological disorders, severe medical conditions, recent cancer or substance abuse, high blood pressure, renal failure, severe sensory impairments, psychiatric diagnoses like schizophrenia or bipolar disorder.

Inclusion Criteria

You need to test positive for herpes antibodies during screening.

You have a positive amyloid scan or a positive CSF biomarker for Alzheimer's disease.

I am able to understand and make decisions about my treatment.

Exclusion Criteria

I do not have major neurological disorders like Parkinson's or multiple sclerosis.

You have thoughts of hurting yourself, or a plan to do so, as determined by a doctor.

You have had a drinking or drug problem in the past 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive oral valacyclovir or placebo for 52 weeks

52 weeks

Visits at Week 0, Week 12, Week 26, and Week 52

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Valacyclovir

Trial Overview The study tests Valacyclovir (an antiviral medication) against a placebo in individuals with Mild Cognitive Impairment to see if it affects the progression of cognitive issues related to Alzheimer's disease. It's a double-blind trial where neither participants nor researchers know who gets the real medicine versus the sugar pill during the year-long study.

How Is the Trial Designed?

Group I: Valacyclovir Active Control 1 Intervention

Oral valacyclovir will be distributed in 500mg caplets. Patients will take 8 caplets per day (total dose: 4 grams per day) for 52 weeks.

Group II: Placebo Placebo Group 1 Intervention

The oral placebo (sugar pill) will be distributed in 500mg caplets. Patients will take 8 caplets per day for 52 weeks.

Who Is Running the Clinical Trial?

New York State Psychiatric Institute

Lead Sponsor

Trials

481

Recruited

154,000+

Alzheimer's Association

Collaborator

Trials

103

Recruited

44,300+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04710030

NCT04710030 | Valacyclovir for Mild Cognitive Impairment Patients treated with valacyclovir are hypothesized to show smaller decline in cognition and functioning compared to placebo, and, using 18F-Florbetapir PET ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7045215/

Valacyclovir Treatment of Alzheimer's Disease (VALAD) Trial ... This study will evaluate whether antiviral treatment with valacyclovir can improve cognition and function in patients with HSV seropositive ...

3. cuimc.columbia.edu cuimc.columbia.edu/news/antiviral-treatment-fails-slow-early-stage-alzheimers

Antiviral Treatment Fails to Slow Early-Stage Alzheimer's After 18 months, the researchers found that patients taking the placebo performed slightly better on cognitive tests than the valacyclovir group ...

4. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc2.12264

High‐dose valacyclovir treatment in patients with early‐stage ... Four weeks of high-dose valacyclovir treatment was safe, tolerable, and feasible in early-stage AD. Our findings may guide future trial design.

5. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/Valacyclovir_%28drug%29_%281%29.pdf

Valacyclovir Secondary outcomes included change in cognitive function as assessed ... cognitive function in patients with mild cognitive impairment or early dementia.

6. cureus.com cureus.com/articles/358588-a-dose-too-far-valacyclovirs-surprising-side-effect

A Dose Too Far: Valacyclovir's Surprising Side Effect Although generally considered safe, rare cases of psychiatric adverse effects, including psychosis, have been reported. The precise mechanism ...