To Rescue Cognition With Valaciclovir
Primary Purpose
Schizophrenia, Psychosis
Status
Completed
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Valaciclovir
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring schizophrenia, treatment, inflammation, neuroinflammation, hippocampal
Eligibility Criteria
Inclusion Criteria:
- Age above 18
- Written informed consent for participation
- Diagnosis: schizophrenia, all subtypes (DSM-IV 295.xx)
- Psychosis, characterised by a total score on the positive scale on the PANSS above 14. In addition, a minimal score of 4 or more on an item of the positive scale.
Exclusion Criteria:
- The use of benzodiazepines. Benzodiazepines have affinity for the peripheral benzodiazepine receptor which is the target receptor for [11C]-PK11195 PET and they can thus interfere with the PET study.
- The use of a nonsteroidal antiinflammatory drug or paracetamol in week before the PET scans and during the treatment of valaciclovir
- The use of anticoagulants or having coagulation disorder
- Use of somatic medication which may affect the immune system (e.g. corticoids, anti-inflammatory drugs, immune suppressive drugs)
- Use of any investigational drug
- Current or recent (<1 year) alcohol or substance abuse
- Disturbed kidney function
- Disturbed liver function
- Current or recent (<4 weeks) infectious or inflammatory disease
- Current systemic disease
- Major metabolic disease (diabetes, hyper- or hypothyroidism, Cushing disease or Addison disease)
- Somatic, organic or neurological disorder
- Participation in a scientific research study (<1 year) involving radiation
- Claustrophobia
Presence of materials in the body that can be magnetized, like:
- A pacemaker
- Metal fragments
- Shunts
- Artificial heart valves
- Vascular clips
- Fixed hearing aid
- Tattoos containing metal
- Hair implants
- Artificial dentures
Sites / Locations
- University Medical Center Groningen, University of Groningen
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Valaciclovir
Placebo
Arm Description
The patients in the experimental group will be treated with 4 times 2 grams valaciclovir per day for seven days.
Patient receives placebo four times a day for seven days.
Outcomes
Primary Outcome Measures
To find a pre- and post-valaciclovir treatment difference in hippocampal inflammation
The main objective is to find a pre- and post-valaciclovir treatment difference in hippocampal inflammation, as measured with positron emission tomography, in schizophrenic patients exposed to a psychotic episode.
Secondary Outcome Measures
To find pre- and post-treatment [11C]-PK11195 binding potential in other brain areas than the hippocampus.
Secondary study parameters are the antibodies against common viruses and the pre- and post-treatment [11C]-PK11195 binding potential in other brain areas than the hippocampus. This is also measured by means of PET and MRI
To find whether the patients hae antibodies against common viruses
Secondary study parameters are the antibodies against common viruses, measured in the blood samples.
To find a pre- and post-valaciclovir treatment difference in hippocampal inflammation
The secondary objective is to improve cognition by the supposed anti-inflammatory effect on the hippocampus of valaciclovir, this will be measured by means of PANSS, the attention, memory and IQ test.
Full Information
NCT ID
NCT01364792
First Posted
May 31, 2011
Last Updated
November 30, 2016
Sponsor
University Medical Center Groningen
Collaborators
Stanley Medical Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT01364792
Brief Title
To Rescue Cognition With Valaciclovir
Official Title
A Double Blind Placebo Controlled Study of Valaciclovir in Treatment of Psychosis in Patients With Schizophrenia
Study Type
Interventional
2. Study Status
Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
April 2011 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
August 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Medical Center Groningen
Collaborators
Stanley Medical Research Institute
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a one-week, randomized, double blind add-on study of valaciclovir versus placebo in 24 clinical patients with Schizophrenia according to DSM IV, currently experiencing psychosis as is defined by the positive items of the Positive and Negative Syndrome Scale (PANNS) score, being five or higher on one item or four on two items of this scale. Each patient will be randomized to double blind treatment with either valaciclovir or placebo for one week.
The main objective is to find a pre- and post-valaciclovir treatment difference in hippocampal inflammation, as measured with positron emission tomography. The secondary objective is to improve cognition by the supposed anti-inflammatory effect on the hippocampus of valaciclovir. This is measured by pre- and post-treatment performance on the PANSS, the attention and memory test.
Both the treatment team and the patient will remain blinded during the course of the study. Following the active treatment phase, patients will receive treatment as clinically indicated.
Detailed Description
Rationale:
Schizophrenia is a chronic and disabling brain disease, with unknown aetiology. Recently, we have shown the presence of an inflammatory process in the hippocampus of schizophrenic patients during psychosis. In addition, we found evidence for the presence of herpes viruses in the temporal lobe of schizophrenic patients during psychosis. Taken together, we hypothesize that the hippocampal inflammation is caused by the presence of herpes viruses, and that this inflammation interferes with the normal involvement of the hippocampus in cognition. Anti-viral treatment, with valaciclovir, that reduces the activity herpes viruses in the hippocampus could reduce the neuroinflammation and thus improve cognition and symptoms in schizophrenia.
Objective:
The main objective is to find a pre- and post-valaciclovir treatment difference in hippocampal inflammation, as measured with positron emission tomography, in schizophrenic patients exposed to a psychotic episode. The secondary objective is to improve cognition by the supposed anti-inflammatory effect on the hippocampus of valaciclovir.
Study design:
The study is double-blind randomized placebo-controlled trial. Study population: For this study, 24 male patients compliant with schizophrenia disorder (DSM-IV codes 295.xx) are included that have a psychosis. The age should be above 18 and patients of all ethnic backgrounds can be included.
Intervention (if applicable):
Of the 24 included patients, 12 patients will receive 8 g (4x2 g per day) of valaciclovir daily for a period of 7 consecutive days and 12 patients will receive 8 g (4x2 g per day) of placebo daily for 7 consecutive days.
Main study parameters/endpoints: The main study parameters are the pre-and post-treatment [11C]-PK11195 binding potential (an inflammatory marker) in the hippocampus, the pre- and post-treatment performance on the PANSS, the attention, memory and IQ test.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
Patients will be admitted to a psychiatric hospital, if not already admitted as a part of their regular treatment, and treated with valaciclovir for seven consecutive 24-h periods. Patients have to fill in a questionnaire and have to undergo a part of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) interview and a MRI scan once, and have to undergo a PANSS interview, attention, memory and IQ tests, and PET scan twice. A total of 345 ml of blood will be taken for the determination of kidney and liver function, herpes virus antibodies, acyclovir levels in blood and for the PET scan data-analysis. Treatment with valaciclovir may cause nausea and headache but the risk of serious side effects is low (<1 out of 10.000). For the PET scan, the arterial catheterization can cause discomfort and the patients are exposed to radioactivity with minor to moderate risk. The patients treated with valaciclovir can have direct benefit form the treatment, because it may reduce symptoms. In general, when this study finds evidence for the involvement of herpes viruses in schizophrenia, this can lead to improved treatment of these patients in the near future.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Psychosis
Keywords
schizophrenia, treatment, inflammation, neuroinflammation, hippocampal
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Valaciclovir
Arm Type
Experimental
Arm Description
The patients in the experimental group will be treated with 4 times 2 grams valaciclovir per day for seven days.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patient receives placebo four times a day for seven days.
Intervention Type
Drug
Intervention Name(s)
Valaciclovir
Other Intervention Name(s)
Zelitrex, Anti-viral drugs
Intervention Description
4 times 2 grams valaciclovir per day, administrated orally, for seven days.
Primary Outcome Measure Information:
Title
To find a pre- and post-valaciclovir treatment difference in hippocampal inflammation
Description
The main objective is to find a pre- and post-valaciclovir treatment difference in hippocampal inflammation, as measured with positron emission tomography, in schizophrenic patients exposed to a psychotic episode.
Time Frame
8-15 days
Secondary Outcome Measure Information:
Title
To find pre- and post-treatment [11C]-PK11195 binding potential in other brain areas than the hippocampus.
Description
Secondary study parameters are the antibodies against common viruses and the pre- and post-treatment [11C]-PK11195 binding potential in other brain areas than the hippocampus. This is also measured by means of PET and MRI
Time Frame
8-15 days
Title
To find whether the patients hae antibodies against common viruses
Description
Secondary study parameters are the antibodies against common viruses, measured in the blood samples.
Time Frame
8-15 days
Title
To find a pre- and post-valaciclovir treatment difference in hippocampal inflammation
Description
The secondary objective is to improve cognition by the supposed anti-inflammatory effect on the hippocampus of valaciclovir, this will be measured by means of PANSS, the attention, memory and IQ test.
Time Frame
8-15 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age above 18
Written informed consent for participation
Diagnosis: schizophrenia, all subtypes (DSM-IV 295.xx)
Psychosis, characterised by a total score on the positive scale on the PANSS above 14. In addition, a minimal score of 4 or more on an item of the positive scale.
Exclusion Criteria:
The use of benzodiazepines. Benzodiazepines have affinity for the peripheral benzodiazepine receptor which is the target receptor for [11C]-PK11195 PET and they can thus interfere with the PET study.
The use of a nonsteroidal antiinflammatory drug or paracetamol in week before the PET scans and during the treatment of valaciclovir
The use of anticoagulants or having coagulation disorder
Use of somatic medication which may affect the immune system (e.g. corticoids, anti-inflammatory drugs, immune suppressive drugs)
Use of any investigational drug
Current or recent (<1 year) alcohol or substance abuse
Disturbed kidney function
Disturbed liver function
Current or recent (<4 weeks) infectious or inflammatory disease
Current systemic disease
Major metabolic disease (diabetes, hyper- or hypothyroidism, Cushing disease or Addison disease)
Somatic, organic or neurological disorder
Participation in a scientific research study (<1 year) involving radiation
Claustrophobia
Presence of materials in the body that can be magnetized, like:
A pacemaker
Metal fragments
Shunts
Artificial heart valves
Vascular clips
Fixed hearing aid
Tattoos containing metal
Hair implants
Artificial dentures
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert A Schoevers, MD, Prof.
Organizational Affiliation
University Medical Centre Grongingen
Official's Role
Study Chair
Facility Information:
Facility Name
University Medical Center Groningen, University of Groningen
City
Groningen
ZIP/Postal Code
9700
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
19837763
Citation
Doorduin J, de Vries EF, Willemsen AT, de Groot JC, Dierckx RA, Klein HC. Neuroinflammation in schizophrenia-related psychosis: a PET study. J Nucl Med. 2009 Nov;50(11):1801-7. doi: 10.2967/jnumed.109.066647. Epub 2009 Oct 16.
Results Reference
background
PubMed Identifier
21353483
Citation
Yolken RH, Torrey EF, Lieberman JA, Yang S, Dickerson FB. Serological evidence of exposure to Herpes Simplex Virus type 1 is associated with cognitive deficits in the CATIE schizophrenia sample. Schizophr Res. 2011 May;128(1-3):61-5. doi: 10.1016/j.schres.2011.01.020. Epub 2011 Feb 24.
Results Reference
background
PubMed Identifier
14638597
Citation
Dickerson FB, Boronow JJ, Stallings CR, Origoni AE, Yolken RH. Reduction of symptoms by valacyclovir in cytomegalovirus-seropositive individuals with schizophrenia. Am J Psychiatry. 2003 Dec;160(12):2234-6. doi: 10.1176/appi.ajp.160.12.2234.
Results Reference
background
PubMed Identifier
19008077
Citation
Dickerson FB, Stallings CR, Boronow JJ, Origoni AE, Sullens A, Yolken RH. Double blind trial of adjunctive valacyclovir in individuals with schizophrenia who are seropositive for cytomegalovirus. Schizophr Res. 2009 Feb;107(2-3):147-9. doi: 10.1016/j.schres.2008.10.007. Epub 2008 Nov 12.
Results Reference
background
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To Rescue Cognition With Valaciclovir
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