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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02997982
• Date of registration: 06/12/2016
• Prospective Registration: No
• Primary sponsor: Hugo Lovheim
• Public title: Feasibility and Effects of Valaciclovir Treatment in Persons With Early Alzheimer's Disease VALZ-Pilot
• Scientific title: Feasibility and Effects on Markers in Spinal Fluid in Persons With Early Alzheimer's Disease When Treated With Valaciclovir - Open Fas II Pilot Study (VALZ-Pilot)
• Date of first enrolment: December 2016
• Target sample size: 33
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02997982
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Sweden

Contacts

• Name: Hugo Lövheim, M.D., Ph.D.
• Affiliation: Umeå University, Umeå, Sweden

Key inclusion & exclusion 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.



Age minimum: 65 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Herpes Simplex

Mild Cognitive Impairment

Alzheimer Disease

Intervention(s)

Drug: Valaciclovir 500Mg Tablet

Primary Outcome(s)

Cerebrospinal fluid (CSF) Total Tau [Time Frame: Baseline and treatment day 28]

Secondary Outcome(s)

Cerebrospinal fluid (CSF) acyclovir concentration [Time Frame: Treatment day 28]

Serum acyclovir concentration [Time Frame: Treatment day 28]

Cerebrospinal fluid (CSF) Amyloid beta 1-42 [Time Frame: Baseline and treatment day 28]

Cerebrospinal fluid (CSF) phosphorylated Tau (p-Tau) [Time Frame: Baseline and treatment day 28]

PET/CT: [18F]-FHBG accumulation [Time Frame: One week before and one week after drug treatment]

PET/CT: [18F]-FHBG accumulation within the central nervous system (CNS) [Time Frame: One week before drug treatment start]

Proportion completing the [18F]-FHBG-PET/CT investigations [Time Frame: For the investigations one week before and one week after drug treatment]

Mini Mental State Examination - Swedish Revision (MMSE-SR) [Time Frame: Baseline and treatment day 28]

PET/CT: Location of [18F]-FHBG accumulation [Time Frame: One week before drug treatment start]

Cerebrospinal fluid (CSF) Neurofilament light chain (NFL) [Time Frame: Baseline and treatment day 28]

Proportion completing the 28 days treatment with valaciclovir at specified doses [Time Frame: Treatment day 28]

Cerebrospinal fluid (CSF) 9-carboxymethoxymethylguanine (CMMG) concentration [Time Frame: Treatment day 28]

Serum 9-carboxymethoxymethylguanine (CMMG) concentration [Time Frame: Treatment day 28]

Secondary ID(s)

UmU-2016-390-31M

2016-002317-22

Source(s) of Monetary Support

Please refer to primary and secondary sponsors