Feasibility and Effects of Valaciclovir Treatment in Persons With Early Alzheimer's Disease

NCT02997982 | Completed Phase 2 DMC

• 2 other identifiers: UmU-2016-390-31M2016-002317-22
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 2

Brief Summary

This study investigates the effects of Valaciclovir treatment to individuals with Alzheimer's disease or Mild Cognitive Impairment of Alzheimer's Disease Type. It is an open pilot trial where 36 participants will receive 4 weeks of Valaciclovir treatment. Participants will be investigated using different measures before and after the treatment period.

Conditions

Alzheimer Disease; Mild Cognitive Impairment; Herpes Simplex

Keywords

Alzheimer's Disease; Herpes Simplex Virus; HSV; Antiviral Drugs

Outcome Measures

Primary Outcomes (1)

• Cerebrospinal fluid (CSF) Total Tau

  Change in CSF Total Tau between samples taken before and after drug treatment

  Baseline and treatment day 28

Secondary Outcomes (13)

• Cerebrospinal fluid (CSF) Neurofilament light chain (NFL)

  Baseline and treatment day 28

• Cerebrospinal fluid (CSF) phosphorylated Tau (p-Tau)

  Baseline and treatment day 28

• Cerebrospinal fluid (CSF) Amyloid beta 1-42

  Baseline and treatment day 28

• PET/CT: [18F]-FHBG accumulation within the central nervous system (CNS)

  One week before drug treatment start

• PET/CT: Location of [18F]-FHBG accumulation

  One week before drug treatment start

Study Arms (1)

Valaciclovir treatment

EXPERIMENTAL

Valaciclovir 500Mg Tablet

Drug: Valaciclovir 500Mg Tablet

Interventions

Valaciclovir 500Mg Tablet DRUG

Valaciclovir treatment (oral, 500 mg tablets). First week: 500 mg three times daily, second to fourth week: 1000 mg three times daily.

Also known as: Valtrex (R)

Valaciclovir treatment

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Man or women, age ≥ 65 years
• Ability to take a stand and to make and to sign an informed consent to participate in the study. This implies that a person with MMSE (Mini Mental State Examination) \< 18 will probably not be included.
• Diagnosed with Alzheimer's disease or mild cognitive impairment due to Alzheimer's disease. At least one brain imaging examination should have been done (CT, MR, SPECT or PET/CT) and at least one objective finding should support the diagnosis beyond specific medical history. Reduced perfusion or reduced metabolism bilaterally temporally, hippocampal atrophy or pathological markers for Alzheimer's disease in cerebrospinal fluid is such findings. Persons with vascular brain disorders e.g. severe white matter changes or previous brain infarction will not be included but those with white matter changes considered normal for their age can be included.
• Positive for anti-HSV (Herpes Simplex Virus) Immunoglobulin G (IgG) in plasma, i.e. carrier of HSV.
• Hetero or Homozygote for allele 4 of gene Apolipoprotein E.
• Stable over all medication including medication for Alzheimer's disease (rivastigmine, galantamin, donepezil or memantin) for at least one month.
• No known allergy or oversensitivity against valaciclovir or aciclovir.
• Ability to independently or by support from relative or other caretaker comply to study drug.

You may not qualify if:

• Renal insufficiency with estimated GFR (Glomerular Filtration Rate) ≤ 30 ml/min/1.73m2
• Ongoing treatment with anticoagulants (Warfarin, low molecular heparin or other anticoagulant agents). Antiplatelet agents in recommended dose are accepted (i.e. Acetylsalicylic acid 75 mgx1)
• Life expectancy \< 1 year due to other comorbidity
• Ongoing severe somatic condition that might interfere with the patients participation in the study (i.e. ongoing cancer treatment)
• Ongoing illness that makes exams in a supine position impossible (i.e. severe heart failure, severe back pain).
• Dementia diagnosis other than Alzheimer's disease, including Vascular dementia.
• Other known neurological/neurodegenerative disorder (i.e. brain tumor, MS (Multiple sclerosis), ALS (amyotrophic lateral sclerosis))
• Claustrophobia or other contraindication for doing a PET/CT scanning.
• Depression or other psychiatric illness that requires treatment (i.e. severe psychosis or other illness with equal grade of seriousness)
• Dementia or cognitive dysfunction to such extent that an informed consent is impossible to obtain, corresponding to about MMSE-SR (Mini Mental State Examination-Swedish revision) \<18.
• History of substance abuse (i.e. central nervous system stimulants or alcohol). Nicotine use is accepted.
• Not willing to participate in the study.

Sponsors & Collaborators

• Hugo Lovheim: lead

Study Sites (2)

Geriatric Centre, University Hospital in Umeå

Umeå, Västerbotten County, 90185, Sweden

Location

Memory Clinic, Uppsala University Hospital

Uppsala, Sweden

Location

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction; Herpes Simplex

Interventions

Valacyclovir; Tablets

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Skin Diseases, Viral; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Hugo Lövheim, M.D., Ph.D.

  Umeå University, Umeå, Sweden

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: December 6, 2016
• First Posted: December 20, 2016
• Study Start: December 1, 2016
• Primary Completion: March 4, 2020
• Study Completion: March 4, 2020
• Last Updated: April 3, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2)