VALZ-Pilot

CompletedPhase 2

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

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)

Lead sponsor

Hugo Lovheim

Asset

Valacyclovir

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease, MCI / preclinical Alzheimer’s

Key I/E criterion

•MCI due to AD

Primary endpoint

•Cerebrospinal fluid (CSF) Total Tau

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Eudract number2016-002317-22

NCT IDNCT02997982

Org study IDUmU-2016-390-31M

Timeline

Milestones

Study start2016-12actual (month precision)

Study first posted2016-12-20estimated

Primary completion2020-03-04actual

Study completion2020-03-04actual

Last update posted2020-04-03actual

Assets

Drug assets

Valacyclovir

Study populations

Who this study enrolls

Alzheimer’s diseaseMCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age65 Years

SexAll

Healthy volunteersNot accepted

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.

Endpoints (14)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Other (unclassified)

Tau biomarkers

Fluid / digital biomarkers

Global cognition

Amyloid biomarkers

Neurodegeneration biomarkers

Other clinical outcomes

Global cognition

1 endpoint

Secondary/protocol endpoint

Mini Mental State Examination - Swedish Revision (MMSE-SR)

Time frame:Baseline and treatment day 28

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Amyloid biomarkers

1 endpoint

Secondary/protocol endpoint

Cerebrospinal fluid (CSF) Amyloid beta 1-42

Time frame:Baseline and treatment day 28

change from baseline, improvement

Tau biomarkers

2 endpoints

Primary/protocol endpoint

Cerebrospinal fluid (CSF) Total Tau

Time frame:Baseline and treatment day 28

change from baseline, improvement

Secondary/protocol endpoint

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

Time frame:Baseline and treatment day 28

change from baseline, improvement

Neurodegeneration biomarkers

1 endpoint

Secondary/protocol endpoint

Cerebrospinal fluid (CSF) Neurofilament light chain (NFL)

Time frame:Baseline and treatment day 28

Neurofilament light (NfL)

change from baseline, improvement

Fluid / digital biomarkers

2 endpoints

Secondary/protocol endpoint

Cerebrospinal fluid (CSF) acyclovir concentration

Time frame:Treatment day 28

concentration, descriptive

Secondary/protocol endpoint

Cerebrospinal fluid (CSF) 9-carboxymethoxymethylguanine (CMMG) concentration

Time frame:Treatment day 28

concentration, descriptive

Other clinical outcomes

1 endpoint

Secondary/protocol endpoint

Proportion completing the 28 days treatment with valaciclovir at specified doses

Time frame:Treatment day 28

threshold achievement, improvement