Attenuated or Transient PsychosisPhase 2AttenPsycNCT02026947
Sodium Benzoate for Treatment of Attenuated/Transient Psychosis. A Randomized Placebo-controlled Trial.
A Phase 2 study testing Sodium Benzoate in people with Attenuated or Transient Psychosis, run by Niuvanniemi Hospital at 2 sites in Finland.
Trial summary
The aim of this study is to investigate whether sodium benzoate is superior to placebo in decreasing symptoms among patients with attenuated/transient psychosis. A total of 140 patients will be randomized in 1:1 ratio to receive sodium benzoate 1 g/day or placebo for 12 weeks. Read more about this study
- Who is it for?
- Ages 15 to 30 years
- Conditions the study is for
- Attenuated or Transient Psychosis
- What is being tested?
- Sodium Benzoate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 2 sitesFinland
- Study dates
- Feb 2014to Dec 2016
- 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 15 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age is from 15 to 30 years
- Meet at least 1 criteria for either of following groups:
- Group a. Attenuated Psychotic Symptoms: Symptom scores of 3 on the PANSS delusions scale, 2-3 on the PANSS hallucinations scale, 3-4 on PANSS suspiciousness, or 3-4 on PANSS conceptual disorganization scale (frequency of symptoms ≥ 2 times/wk for a period of at least 1 week and not longer than 5 years, to have occurred within the last year)
- Group b. Transient Psychosis: Symptoms scores of ≥ 4 on PANSS hallucinations scale, ≥ 4 on PANSS delusions scale, or ≥ 5 on PANSS conceptual disorganization scale (symptoms not sustained beyond a week and resolved without antipsychotic medication within the last year)
Who cannot join
- a history of a previous psychotic disorder or manic episode (both treated or untreated);
- substance-induced psychotic disorder;
- acute suicidal or aggressive behavior;
- a current DSM-IV diagnosis of substance dependence (except cannabis dependence);
- neurological disorders (e.g., epilepsy);
- IQ of less than 70 (no diagnosis of mental retardation as verified by school performance);
Show all 11Show fewer
- previous treatment with an antipsychotic or mood-stabilizing agent (>1 week);
- pregnancy or inadequate pregnancy prevention among sexually active females,
- history of allergy or severe adverse events for sodium benzoate;
- laboratory values more than 10% outside the normal range for transaminases, thyroid hormones, or C-reactive protein; and
- another severe intercurrent illness that may have put the person at risk or influenced the results of the trial or affected their ability to take part in the trial. Use of benzodiazepine-derivatives is allowed during the trial.
Trial locations and contacts
2 sites in 1 country.
Finland2 sites
HUS Health Care District
Helsinki
Varsinais-Suomi and Satakunta Health Care District
Turku
About this study
The aim of this study is to investigate whether sodium benzoate is superior to placebo in decreasing symptoms among patients with attenuated/transient psychosis. A total of 140 patients will be randomized in 1:1 ratio to receive sodium benzoate 1 g/day or placebo for 12 weeks. Concerning statistical power, the number of patients is sufficient to obtain statistical significance for a clinically meaningful effect size of 0.40 (Cohen's d). The primary outcome measure is change in PANSS sum score of delusions, hallucinations, suspiciousness and conceptual disorganization (the PANSS items that are inclusion criteria) at week 12. Change in CGI score at week 12 is the other primary outcome measure. The secondary outcome measures are change in PANSS total score at week 12, CGI score at week 24, and GAF at weeks 12 and 24.
Read the detailed description
Early treatment of psychotic disorders results in better outcome, and several small randomized controlled trials (RCTs) have indicated that pharmacological treatment of prodromal patients with subthreshold psychosis might prevent transition to psychotic disorders. Use of risperidone had statistically significant effect at 6 months, but not at 12 months, and olanzapine has shown only a beneficial trend. The use of antipsychotics for the prevention of psychosis is controversial due their adverse effects and, therefore, use of better-tolerated agents such as natural compounds like benzoid acid or omega fatty acids might be a promising approach.
Glutamatergic hypothesis has gained increasing support explaining symptoms of schizophrenia, and hypofunction of N-methyl-D-aspartate (NMDA) receptor is considered nowadays a major factor in the pathophysiology of the disease. Several NMDA-enhancing agents such as glycine, D-alanine, D-serine, sarcosine and bitopertin have shown beneficial effect as add-on treatments to antipsychotics. D-amino acid oxidase (DAAO) metabolizes D-alanine and D-serine, which are co-agonists of NMDA-receptor, and, therefore, decreasing DAAO activity results into enhancement of NMDA-receptor function. Recently, a randomized controlled trial in 52 patients with chronic schizophrenia was well tolerated and showed a robust beneficial effect of DAAO inhibitor sodium benzoate (1 g/d) as compared with placebo (effect size 1.76 for PANSS total scores; Tsai et al. 2012).
The aim of this study is to investigate whether sodium benzoate is superior to placebo in decreasing symptoms among patients with attenuated/transient psychosis. A total of 140 patients will be randomized in 1:1 ratio to receive sodium benzoate 1 g/day or placebo for 12 weeks. Concerning statistical power, the number of patients is sufficient to obtain statistical significance for a clinically meaningful effect size of 0.40 (Cohen's d). The primary outcome measure is change in PANSS sum score of delusions, hallucinations, suspiciousness and conceptual disorganization (the PANSS items that are inclusion criteria) at week 12. Change in CGI score at week 12 is the other primary outcome measure. The secondary outcome measures are change in PANSS total score at week 12, CGI score at week 24, and GAF at weeks 12 and 24.
An interim analysis will be done after obtaining results from the first 40 patients. If the effect size (Cohen's d) for primary outcome measures is less than 0.30, the study will be stopped prematurely.
- Conditions
- Attenuated or Transient Psychosis
- Being tested
- Sodium Benzoate, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium BenzoateDrug
0.5 g/day during the first week, 1.0 g/day for the next 11 weeks. One capsule at the morning for the first week. One capsule at the morning and one at the evening for 2-12 weeks.
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | In both arms, one capsule at the morning for the first week. One capsule at the morning and one at the evening for the weeks 2-12. Receives: Drug: Placebo |
| Sodium benzoate | Experimental | 0.5 g/day during the first week, 1.0 g/day for the next 11 weeks. One capsule at the morning for the first week. One capsule at the morning and one at the evening for 2-12 weeks. Receives: Drug: Sodium Benzoate; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
change in PANSS sum score of delusions, hallucinations, suspiciousness, and conceptual disorganization
change in PANSS sum score of delusions, hallucinations, suspiciousness and conceptual disorganization (the PANSS items that are inclusion criteria)
Measured: baseline - week 12
change in Clinical Global Improvement Scale (CGIS)
Measured: baseline - week 12
Secondary outcomes (3)
change in Clinical Global Improvement (CGI)
Measured: baseline - week 24
change in Positive and Negative Syndrome Scale (PANSS), Total score
Measured: baseline - week 12
change in Global Assessment of Functioning (GAF)
Measured: baseline - weeks 12 and 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2014 (estimated)
- Study startFeb 2014
- Primary completionDec 2016 (estimated)
- Study completionDec 2016 (estimated)
Why it stopped: We did not commence the trial because there were no patients who could fulfill the inclusion criteria.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Attenuated or Transient PsychosisStudies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Niuvanniemi Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Karolinska Institutet
- Responsible party
- Principal investigator, Jari Tiihonen, Niuvanniemi Hospital
- Investigators
- Jari Tiihonen, MD, PhD, Principal investigator, Niuvanniemi Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02026947
- Sponsor's protocol ID
- 3418363
- Other IDs
- 2013-000458-23
- Acronym
- AttenPsyc
- Status last verified
- Apr 2014
- First submitted
- 27 Dec 2013
- Last updated
- 10 Apr 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sodium Benzoate for Treatment of Attenuated/Transient Psychosis. A Randomized Placebo-controlled Trial.
- ClinicalTrials.gov ID
- NCT02026947
- Acronym / sponsor ID
- AttenPsyc / 3418363
- Conditions
- Attenuated or Transient Psychosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: We did not commence the trial because there were no patients who could fulfill the inclusion criteria.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Niuvanniemi HospitalUniversity, hospital or other
- Collaborators
- Karolinska Institutet
- Study start
- Feb 2014
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 3 Jan 2014 (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.
The aim of this study is to investigate whether sodium benzoate is superior to placebo in decreasing symptoms among patients with attenuated/transient psychosis. A total of 140 patients will be randomized in 1:1 ratio to receive sodium benzoate 1 g/day or placebo for 12 weeks. Concerning statistical power, the number of patients is sufficient to obtain statistical significance for a clinically meaningful effect size of 0.40 (Cohen's d). The primary outcome measure is change in PANSS sum score of delusions, hallucinations, suspiciousness and conceptual disorganization (the PANSS items that are inclusion criteria) at week 12. Change in CGI score at week 12 is the other primary outcome measure. The secondary outcome measures are change in PANSS total score at week 12, CGI score at week 24, and GAF at weeks 12 and 24.
Detailed description
Early treatment of psychotic disorders results in better outcome, and several small randomized controlled trials (RCTs) have indicated that pharmacological treatment of prodromal patients with subthreshold psychosis might prevent transition to psychotic disorders. Use of risperidone had statistically significant effect at 6 months, but not at 12 months, and olanzapine has shown only a beneficial trend. The use of antipsychotics for the prevention of psychosis is controversial due their adverse effects and, therefore, use of better-tolerated agents such as natural compounds like benzoid acid or omega fatty acids might be a promising approach.
Glutamatergic hypothesis has gained increasing support explaining symptoms of schizophrenia, and hypofunction of N-methyl-D-aspartate (NMDA) receptor is considered nowadays a major factor in the pathophysiology of the disease. Several NMDA-enhancing agents such as glycine, D-alanine, D-serine, sarcosine and bitopertin have shown beneficial effect as add-on treatments to antipsychotics. D-amino acid oxidase (DAAO) metabolizes D-alanine and D-serine, which are co-agonists of NMDA-receptor, and, therefore, decreasing DAAO activity results into enhancement of NMDA-receptor function. Recently, a randomized controlled trial in 52 patients with chronic schizophrenia was well tolerated and showed a robust beneficial effect of DAAO inhibitor sodium benzoate (1 g/d) as compared with placebo (effect size 1.76 for PANSS total scores; Tsai et al. 2012).
The aim of this study is to investigate whether sodium benzoate is superior to placebo in decreasing symptoms among patients with attenuated/transient psychosis. A total of 140 patients will be randomized in 1:1 ratio to receive sodium benzoate 1 g/day or placebo for 12 weeks. Concerning statistical power, the number of patients is sufficient to obtain statistical significance for a clinically meaningful effect size of 0.40 (Cohen's d). The primary outcome measure is change in PANSS sum score of delusions, hallucinations, suspiciousness and conceptual disorganization (the PANSS items that are inclusion criteria) at week 12. Change in CGI score at week 12 is the other primary outcome measure. The secondary outcome measures are change in PANSS total score at week 12, CGI score at week 24, and GAF at weeks 12 and 24.
An interim analysis will be done after obtaining results from the first 40 patients. If the effect size (Cohen's d) for primary outcome measures is less than 0.30, the study will be stopped prematurely.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboIn both arms, one capsule at the morning for the first week. One capsule at the morning and one at the evening for the weeks 2-12. |
| Sodium benzoate | Experimental | Drug: Sodium Benzoate, Drug: Placebo0.5 g/day during the first week, 1.0 g/day for the next 11 weeks. One capsule at the morning for the first week. One capsule at the morning and one at the evening for 2-12 weeks. |
Who may qualify
- Ages
- 15 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Age is from 15 to 30 years
- Meet at least 1 criteria for either of following groups:
- Group a. Attenuated Psychotic Symptoms: Symptom scores of 3 on the PANSS delusions scale, 2-3 on the PANSS hallucinations scale, 3-4 on PANSS suspiciousness, or 3-4 on PANSS conceptual disorganization scale (frequency of symptoms ≥ 2 times/wk for a period of at least 1 week and not longer than 5 years, to have occurred within the last year)
- Group b. Transient Psychosis: Symptoms scores of ≥ 4 on PANSS hallucinations scale, ≥ 4 on PANSS delusions scale, or ≥ 5 on PANSS conceptual disorganization scale (symptoms not sustained beyond a week and resolved without antipsychotic medication within the last year)
Key exclusion criteria (11 listed)
- a history of a previous psychotic disorder or manic episode (both treated or untreated);
- substance-induced psychotic disorder;
- acute suicidal or aggressive behavior;
- a current DSM-IV diagnosis of substance dependence (except cannabis dependence);
- neurological disorders (e.g., epilepsy);
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 |
|---|---|---|
| Sodium Benzoate0.5 g/day during the first week, 1.0 g/day for the next 11 weeks. One capsule at the morning for the first week. One capsule at the morning and one at the evening for 2-12 weeks. | Drug | Sodium benzoate |
| Placebo | Drug | Placebo, Sodium benzoate |
Primary outcome
change in PANSS sum score of delusions, hallucinations, suspiciousness, and conceptual disorganization
Time frame: baseline - week 12
change in PANSS sum score of delusions, hallucinations, suspiciousness and conceptual disorganization (the PANSS items that are inclusion criteria)
change in Clinical Global Improvement Scale (CGIS)
Time frame: baseline - week 12
3 secondary outcomes
change in Clinical Global Improvement (CGI)
Time frame: baseline - week 24
change in Positive and Negative Syndrome Scale (PANSS), Total score
Time frame: baseline - week 12
change in Global Assessment of Functioning (GAF)
Time frame: baseline - weeks 12 and 24
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2014.
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.
Jari Tiihonen, MD, PhD principal investigator
Niuvanniemi Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sodium Benzoate in people with Attenuated or Transient Psychosis, run by Niuvanniemi Hospital at 2 sites in Finland.
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 11 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: withdrawn, as of the sponsor's last update on 10 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Finland. 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 was withdrawn before enrolling participants, so there are no results.
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?
change in PANSS sum score of delusions, hallucinations, suspiciousness, and conceptual disorganization (time frame: baseline - week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Apr 2014; AzTrials last refreshed its copy on 8 Nov 2026.