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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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02997982
Recruitment Status : Completed
First Posted : December 20, 2016
Last Update Posted : April 3, 2020
Sponsor:
Information provided by (Responsible Party):
Hugo Lovheim, Umeå University

Tracking Information
First Submitted Date  ICMJE December 6, 2016
First Posted Date  ICMJE December 20, 2016
Last Update Posted Date April 3, 2020
Actual Study Start Date  ICMJE December 2016
Actual Primary Completion Date March 4, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 15, 2016)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 13, 2019)
  • 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
  • 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
  • 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
  • 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?
  • 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?
  • 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
  • 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
  • Cerebrospinal fluid (CSF) acyclovir concentration [ Time Frame: Treatment day 28 ]
    Cerebrospinal fluid (CSF) acyclovir concentration
  • Cerebrospinal fluid (CSF) 9-carboxymethoxymethylguanine (CMMG) concentration [ Time Frame: Treatment day 28 ]
    Concentration of CMMG, main acyclovir metabolite
  • Serum acyclovir concentration [ Time Frame: Treatment day 28 ]
    Serum acyclovir concentration
  • Serum 9-carboxymethoxymethylguanine (CMMG) concentration [ Time Frame: Treatment day 28 ]
    Concentration of CMMG, main acyclovir metabolite
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: December 15, 2016)
  • 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
  • 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
  • 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
  • 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?
  • 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?
  • 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
  • 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
  • Cerebrospinal fluid (CSF) acyclovir concentration [ Time Frame: Treatment day 28 ]
  • Cerebrospinal fluid (CSF) 9-carboxymethoxymethylguanine (CMMG) concentration [ Time Frame: Treatment day 28 ]
    Concentration of CMMG, main acyclovir metabolite
  • Serum acyclovir concentration [ Time Frame: Treatment day 28 ]
  • Serum 9-carboxymethoxymethylguanine (CMMG) concentration [ Time Frame: Treatment day 28 ]
    Concentration of CMMG, main acyclovir metabolite
  • 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
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Feasibility and Effects of Valaciclovir Treatment in Persons With Early Alzheimer's Disease
Official Title  ICMJE 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)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Alzheimer Disease
  • Mild Cognitive Impairment
  • Herpes Simplex
Intervention  ICMJE 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)
Study Arms  ICMJE Experimental: Valaciclovir treatment
Valaciclovir 500Mg Tablet
Intervention: Drug: Valaciclovir 500Mg Tablet
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 1, 2020)
33
Original Estimated Enrollment  ICMJE
 (submitted: December 15, 2016)
36
Actual Study Completion Date  ICMJE March 4, 2020
Actual Primary Completion Date March 4, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 65 Years and older   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02997982
Other Study ID Numbers  ICMJE UmU-2016-390-31M
2016-002317-22 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Hugo Lovheim, Umeå University
Study Sponsor  ICMJE Hugo Lovheim
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Hugo Lövheim, M.D., Ph.D. Umeå University, Umeå, Sweden
PRS Account Umeå University
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP