SchizophreniaPhase 2NCT01364792
To Rescue Cognition With Valaciclovir
A Phase 2 study testing Valaciclovir in people with Schizophrenia and Psychosis, run by University Medical Center Groningen at 1 site in Netherlands.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Schizophrenia, Psychosis
- What is being tested?
- Valaciclovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- Apr 2011to Aug 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 24Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
University Medical Center Groningen, University of Groningen
Groningen, Provincie Groningen, 9700
About this study
Official title: A Double Blind Placebo Controlled Study of Valaciclovir in Treatment of Psychosis in Patients With Schizophrenia
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.
Read the 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.
- Conditions
- Schizophrenia, Psychosis
- Being tested
- Valaciclovir
- Keywords
- schizophrenia, treatment, inflammation, neuroinflammation, hippocampal
- Medical subject headings
- Schizophrenia, Psychotic Disorders, Inflammation, Neuroinflammatory Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ValaciclovirDrug
Also called Zelitrex, Anti-viral drugs
4 times 2 grams valaciclovir per day, administrated orally, for seven days.
| Study group | Role | What they receive |
|---|---|---|
| Valaciclovir | Experimental | The patients in the experimental group will be treated with 4 times 2 grams valaciclovir per day for seven days. Receives: Drug: Valaciclovir |
| Placebo | Placebo comparator | Patient receives placebo four times a day for seven days. Receives: Drug: Valaciclovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 8-15 days
Secondary outcomes (3)
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
Measured: 8-15 days
To find whether the patients hae antibodies against common viruses
Secondary study parameters are the antibodies against common viruses, measured in the blood samples.
Measured: 8-15 days
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.
Measured: 8-15 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2011 (estimated)
- Study startApr 2011
- Primary completionAug 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Stanley Medical Research Institute
- Responsible party
- Principal investigator, Hans C Klein, MD, PhD, psychiatrist, University Medical Center Groningen
- Investigators
- Robert A Schoevers, MD, Prof., Study chair, University Medical Centre Grongingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01364792
- Sponsor's protocol ID
- Valaciclovir-1
- Status last verified
- Nov 2016
- First submitted
- 31 May 2011
- Last updated
- 1 Dec 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 19837763Yolken 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.
PubMed 21353483Dickerson 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.
PubMed 14638597Dickerson 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.
PubMed 19008077
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double Blind Placebo Controlled Study of Valaciclovir in Treatment of Psychosis in Patients With Schizophrenia
- ClinicalTrials.gov ID
- NCT01364792
- Acronym / sponsor ID
- Valaciclovir-1
- Conditions
- Schizophrenia, Psychosis
- Keywords
- schizophrenia, treatment, inflammation, neuroinflammation, hippocampal
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Stanley Medical Research Institute
- Study start
- Apr 2011
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 2 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Valaciclovir | Experimental | Drug: ValaciclovirThe patients in the experimental group will be treated with 4 times 2 grams valaciclovir per day for seven days. |
| Placebo | Placebo comparator | Drug: ValaciclovirPatient receives placebo four times a day for seven days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ValaciclovirAlso: Zelitrex, Anti-viral drugs4 times 2 grams valaciclovir per day, administrated orally, for seven days. | Drug | Placebo, Valaciclovir |
Primary outcome
To find a pre- and post-valaciclovir treatment difference in hippocampal inflammation
Time frame: 8-15 days
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.
3 secondary outcomes
To find pre- and post-treatment [11C]-PK11195 binding potential in other brain areas than the hippocampus.
Time frame: 8-15 days
To find whether the patients hae antibodies against common viruses
Time frame: 8-15 days
To find a pre- and post-valaciclovir treatment difference in hippocampal inflammation
Time frame: 8-15 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2016.
- Background: PubMed 19837763Doorduin 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.
- Background: PubMed 21353483Yolken 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.
- Background: PubMed 14638597Dickerson 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.
- Background: PubMed 19008077Dickerson 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert A Schoevers, MD, Prof. study chair
University Medical Centre Grongingen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Valaciclovir in people with Schizophrenia and Psychosis, run by University Medical Center Groningen at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To find a pre- and post-valaciclovir treatment difference in hippocampal inflammation (time frame: 8-15 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01364792, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2016.