ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 3 for:    herpesvirus | Alzheimer Disease

Feasibility and Effects of Valaciclovir Treatment in Persons With Early Alzheimer's Disease (VALZ-Pilot)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02997982
Recruitment Status : Recruiting
First Posted : December 20, 2016
Last Update Posted : May 2, 2018
Sponsor:
Information provided by (Responsible Party):
Hugo Lovheim, Umeå University

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.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Mild Cognitive Impairment Herpes Simplex Drug: Valaciclovir 500Mg Tablet Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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)
Actual Study Start Date : December 2016
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : April 2019


Arm Intervention/treatment
Experimental: Valaciclovir treatment
Valaciclovir 500Mg Tablet
Drug: 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.
Other Name: Valtrex (R)




Primary Outcome Measures :
  1. Cerebrospinal fluid (CSF) Total Tau [ Time Frame: Baseline and treatment day 28 ]
    Change in CSF Total Tau between samples taken before and after drug treatment


Secondary Outcome Measures :
  1. Cerebrospinal fluid (CSF) Neurofilament light chain (NFL) [ Time Frame: Baseline and treatment day 28 ]
    Change in CSF NFL between samples taken before and after drug treatment

  2. Cerebrospinal fluid (CSF) phosphorylated Tau (p-Tau) [ Time Frame: Baseline and treatment day 28 ]
    Change in CSF p-Tau between samples taken before and after drug treatment

  3. Cerebrospinal fluid (CSF) Amyloid beta 1-42 [ Time Frame: Baseline and treatment day 28 ]
    Change in Amyloid beta 1-42 between samples taken before and after drug treatment

  4. PET/CT: [18F]-FHBG accumulation within the central nervous system (CNS) [ Time Frame: One week before drug treatment start ]
    Can [18F]-FHBG-PET/CT detect replicating HSV infection within the CNS?

  5. PET/CT: Location of [18F]-FHBG accumulation [ Time Frame: One week before drug treatment start ]
    Do [18F]-FHBG accumulation locate to brain areas affected in AD?

  6. PET/CT: [18F]-FHBG accumulation [ Time Frame: One week before and one week after drug treatment ]
    Change in [18F]-FHBG accumulation after, as compared to before, drug treatment

  7. Mini Mental State Examination - Swedish Revision (MMSE-SR) [ Time Frame: Baseline and treatment day 28 ]
    Change in MMSE-SR scores from baseline to after drug treatment

  8. Cerebrospinal fluid (CSF) acyclovir concentration [ Time Frame: Treatment day 28 ]
  9. Cerebrospinal fluid (CSF) 9-carboxymethoxymethylguanine (CMMG) concentration [ Time Frame: Treatment day 28 ]
    Concentration of CMMG, main acyclovir metabolite

  10. Serum acyclovir concentration [ Time Frame: Treatment day 28 ]
  11. Serum 9-carboxymethoxymethylguanine (CMMG) concentration [ Time Frame: Treatment day 28 ]
    Concentration of CMMG, main acyclovir metabolite

  12. Proportion completing the [18F]-FHBG-PET/CT investigations [ Time Frame: For the investigations one week before and one week after drug treatment ]
    Is [18F]-FHBG-PET/CT a feasible examination among persons with Alzheimer's disease

  13. Proportion completing the 28 days treatment with valaciclovir at specified doses [ Time Frame: Treatment day 28 ]
    Feasibility of valaciclovir treatment as measured by the number of participants completing the full treatment period at the specified dose



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02997982


Contacts
Contact: Hugo Lövheim, M.D., Ph.D. +46702979499 hugo.lovheim@umu.se

Locations
Sweden
Geriatric Centre, University Hospital in Umeå Recruiting
Umeå, Västerbotten, Sweden, 90185
Contact: Hugo Lövheim, M.D., Ph.D.    +46702979499    hugo.lovheim@umu.se   
Sponsors and Collaborators
Hugo Lovheim
Investigators
Principal Investigator: Hugo Lövheim, M.D., Ph.D. Umeå University, Umeå, Sweden

Responsible Party: Hugo Lovheim, Associate professor, Umeå University
ClinicalTrials.gov Identifier: NCT02997982     History of Changes
Other Study ID Numbers: UmU-2016-390-31M
2016-002317-22 ( EudraCT Number )
First Posted: December 20, 2016    Key Record Dates
Last Update Posted: May 2, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Hugo Lovheim, Umeå University:
Alzheimer's Disease
Herpes Simplex Virus
HSV
Antiviral Drugs

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders
Herpesviridae Infections
Virus Diseases
Skin Diseases, Viral
Skin Diseases, Infectious
Skin Diseases
Cognitive Dysfunction
Herpes Simplex
Dementia
Tauopathies
DNA Virus Infections
Valacyclovir
Acyclovir
Antiviral Agents
Anti-Infective Agents