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

NCT ID: NCT02997982

Last Updated: 2020-04-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2020-03-04

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.

Detailed Description

This study investigates the effects of valaciclovir treatment to individuals with Alzheimer's disease (AD) or Mild Cognitive Impairment of Alzheimer's Disease Type. It is an open pilot trial where 36 participants will receive 4 weeks of oral valaciclovir treatment. To find 36 persons fulfilling inclusion criteria, up to 120 persons will be screened. Important inclusion criteria are Herpes Simplex Virus (HSV) Immunoglobulin G (IgG)-positivity (HSV carriage), Apolipoprotein E allele 4 carriage and sufficient kidney function (estimated glomerular filtration rate above 30 ml/min). All participants must give their informed consent to participation.

The valaciclovir dose will be 500 mg three times daily the first week and 1000 mg three times daily week 2-4.

Participants will be investigated using different measures before and after the treatment period: Mini Mental State Examination to assess cognitive function, Cerebrospinal fluid biomarkers of Alzheimer's disease and [18F]-FHBG-PET/CT (9-[4-[18F]fluoro-3-(hydroxymethyl)butyl]guanine positron emission tomography/computed tomography)) to possibly indicate active HSV infection within the central nervous system.

Conditions

Alzheimer Disease; Mild Cognitive Impairment; Herpes Simplex

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Valaciclovir treatment

Valaciclovir 500Mg Tablet

Group Type: EXPERIMENTAL

Valaciclovir 500Mg Tablet

Intervention Type: DRUG

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

Interventions

Valaciclovir 500Mg Tablet

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

Intervention Type: DRUG

Other Intervention Names

Valtrex (R)

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hugo Lovheim

OTHER

Sponsor Role: lead

Responsible Party

Hugo Lovheim

Associate professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Hugo Lövheim, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Umeå University, Umeå, Sweden

Locations

Geriatric Centre, University Hospital in Umeå

Umeå, Västerbotten County, Sweden

Memory Clinic, Uppsala University Hospital

Uppsala, , Sweden

Countries

Sweden

Other Identifiers

2016-002317-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

UmU-2016-390-31M

Identifier Type: -

Identifier Source: org_study_id