To Rescue Cognition With Valaciclovir

NCT01364792 | Completed Phase 2

• 1 other identifier: Valaciclovir-1
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia; Psychosis

Keywords

schizophrenia; treatment; inflammation; neuroinflammation; hippocampal

Outcome Measures

Primary Outcomes (1)

• 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.

  8-15 days

Secondary Outcomes (3)

• To find pre- and post-treatment [11C]-PK11195 binding potential in other brain areas than the hippocampus.

  8-15 days

• To find whether the patients hae antibodies against common viruses

  8-15 days

• To find a pre- and post-valaciclovir treatment difference in hippocampal inflammation

  8-15 days

Study Arms (2)

Valaciclovir

EXPERIMENTAL

The patients in the experimental group will be treated with 4 times 2 grams valaciclovir per day for seven days.

Drug: Valaciclovir

Placebo

PLACEBO COMPARATOR

Patient receives placebo four times a day for seven days.

Drug: Valaciclovir

Interventions

Valaciclovir DRUG

4 times 2 grams valaciclovir per day, administrated orally, for seven days.

Also known as: Zelitrex, Anti-viral drugs

Placebo; Valaciclovir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Stanley Medical Research Institute: collaborator

Study Sites (1)

University Medical Center Groningen, University of Groningen

Groningen, Provincie Groningen, 9700, Netherlands

Location

Related Publications (4)

• 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.

  PMID: 19837763 BACKGROUND

• 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.

  PMID: 21353483 BACKGROUND

• 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.

  PMID: 14638597 BACKGROUND

• 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.

  PMID: 19008077 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Inflammation; Neuroinflammatory Diseases

Interventions

Valacyclovir

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Robert A Schoevers, MD, Prof.

  University Medical Centre Grongingen

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Psychiatrist

Study Record Dates

• First Submitted: May 31, 2011
• First Posted: June 2, 2011
• Study Start: April 1, 2011
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: December 1, 2016

Record last verified: 2016-11

Locations

NL (1)