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)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 33
- 试验地点
- 2
- 主要终点
- Cerebrospinal fluid (CSF) Total Tau
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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) <
- •History of substance abuse (i.e. central nervous system stimulants or alcohol). Nicotine use is accepted.
- •Not willing to participate in the study.
研究组 & 干预措施
Valaciclovir treatment
Valaciclovir 500Mg Tablet
干预措施: Valaciclovir 500Mg Tablet (Drug)
结局指标
主要结局
Cerebrospinal fluid (CSF) Total Tau
时间窗: Baseline and treatment day 28
Change in CSF Total Tau between samples taken before and after drug treatment
次要结局
- Mini Mental State Examination - Swedish Revision (MMSE-SR)(Baseline and treatment day 28)
- Cerebrospinal fluid (CSF) acyclovir concentration(Treatment day 28)
- Cerebrospinal fluid (CSF) 9-carboxymethoxymethylguanine (CMMG) concentration(Treatment day 28)
- Serum acyclovir concentration(Treatment day 28)
- Serum 9-carboxymethoxymethylguanine (CMMG) concentration(Treatment day 28)
- Proportion completing the [18F]-FHBG-PET/CT investigations(For the investigations one week before and one week after drug treatment)
- Cerebrospinal fluid (CSF) Amyloid beta 1-42(Baseline and treatment day 28)
- Cerebrospinal fluid (CSF) Neurofilament light chain (NFL)(Baseline and treatment day 28)
- Cerebrospinal fluid (CSF) phosphorylated Tau (p-Tau)(Baseline and treatment day 28)
- PET/CT: [18F]-FHBG accumulation(One week before and one week after drug treatment)
- 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)
- Proportion completing the 28 days treatment with valaciclovir at specified doses(Treatment day 28)
研究者
Hugo Lovheim
Associate professor
Umeå University