Schizoaffective and Schizophreniform DisordersPhase 3NCT01121042
Double Blind, Placebo-Controlled, Randomised Investigation of Ondansetron in Schizophrenia
A Phase 3 study testing Ondansetron in people with Schizoaffective and Schizophreniform Disorders and Schizophrenia, run by Bayside Health at 1 site in Australia.
Trial summary
The aim of this study is to evaluate the overall effectiveness of Ondansetron as an adjunctive or "add-on" medication in the treatment of Schizophrenia. This study is a double blind, placebo-controlled, randomised, 12 week trial. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizoaffective and Schizophreniform Disorders, Schizophrenia
- What is being tested?
- Ondansetron
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 85 participants
- Where
- 1 siteAustralia
- Study dates
- Jul 2010to Aug 2018
- Phase
- Phase 3
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged between 18-65 years of age
- Have a current DSM-IV-TR diagnosis of schizophrenia, schizoaffective of schizophreniform disorders (diagnosis will be confirmed using the MINI Neuropsychiatric Interview)
- Have been treated with a stable and standard dose (as determined by the PORT Treatment Recommendations for schizophrenia [33]) of an atypical antipsychotic agent (not including amisulpride owing to its 5HT3 actions) as their primary antipsychotic treatment for a minimum of eight weeks before entry into the trial
- Are experiencing positive symptoms as evidenced by a score of >15 on the Positive Syndrome Subscale of the PANSS, and/or negative psychotic symptoms as evidenced by a score of >15 on the Negative Syndrome Subscale of the PANSS and /or significant cognitive dysfunction, as evidenced by at least 15 on the cognitive subscale. The cognition subscale used in this study, which included items of G10, G11, G12, P2, N5, and N7 from the PANSS were generated from previous studies.
- Have a level of understanding sufficient to provide informed consent and to communicate with the investigators, study coordinator, and site personnel.
Who cannot join
- Have an unstable medical condition, neurological disorder or an unstable seizure disorder. Any clinical significant electrocardiogram (ECG) abnormality at screening, including sinus bradycardia (ersting heart rate <50 beats per minute), atrial fibrillation, 2nd or 3rd degree AV block (AVB), prolonged ATc (QTcF>450ms in males or >470ms in females) history of congenital long AT syndromes, or risk of Torsades de Pointes because of family history of sudden death.
- Currently pregnant or breastfeeding
- Have a current DSM-IV-TR diagnosis of substance abuse or dependence disorder, or another Axis I disorder
- Regularly use of another 5HT3 antagonist such as metoclopramide, cocaine, tropisetron, granisetron, palonosetron
Trial locations and contacts
1 site in 1 country.
Australia1 site
Monash Alfred Psychiatry Research Centre (MAPrc)
Melbourne, Victoria, 3004
About this study
The aim of this study is to evaluate the overall effectiveness of Ondansetron as an adjunctive or "add-on" medication in the treatment of Schizophrenia. This study is a double blind, placebo-controlled, randomised, 12 week trial.
Read the detailed description
Ondansetron is a medication currently approved by the Australian Therapeutic Goods Administration for the treatment of drug-induced vomiting and nausea. Beyond this traditional use there have been several case reports and small clinical trials advocating the use of Ondansetron in the treatment of adult Schizophrenia. Overall these studies lend support to the use of Ondansetron in conjunction with mainstream antipsychotic medication in improving not only the positive symptoms associated with Schizophrenia but also the 'hard to treat' negative and cognitive symptoms. Furthermore, Ondansetron may also have potential benefits in reducing the adverse motor effects (e.g. tremor, uncontrolled muscle movements) associated with the use of many antipsychotic medications.
60 participants aged 18-65 inclusive with a DSM-IV diagnosis of Schizophrenia, Schizoaffective, or Schizophreniform disorder will be recruited. This study proposes to conduct a randomized, controlled treatment trial to investigate the efficacy of ondansetron as an adjunctive treatment in reducing negative and positive symptoms plus improving cognitive symptoms. There will be an initial screening session to determine participant suitability, a baseline session where the study medication (Ondansetron or Placebo) will be dispensed, followed by three monitoring visits.
The efficacy of Ondansetron will be evaluated by the following instruments:
- Positive and Negative Symptom Scale (PANSS)
- Montgomery-Åsberg Depression Rating Scale (MADRS)
- C-Reactive protein (marker of systematic and brain specific inflammation)
Safety will be assessed through adverse event reporting using the Adverse symptom Checklist (ASC), blood analysis, urinalysis, a 12-lead Electrocardiogram (ECG) and a physical examination. Adverse motor symptoms will also be assessed by the Abnormal Involuntary Movement Scale and the Simpson-Angus Scale. In addition a safety and monitoring committee consisting of research and medical staff external to the project will regularly review adverse events.
- Being tested
- Ondansetron, Placebo
- Medical subject headings
- Psychotic Disorders, Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OndansetronDrug
8mg per day oral capsule
PlaceboDrug
daily oral capsule matched to active study medication. Made form 100% lactose powder
| Study group | Role | What they receive |
|---|---|---|
| Ondansetron | Active comparator | Ondansetron oral capsule 8mg daily Receives: Drug: Ondansetron |
| Placebo | Placebo comparator | Placebo (100% lactose) matched oral capsule Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Positive and Negative Symptom Scale (PANSS)
The PANSS is a widely used, drug-sensitive, valid and reliable measure of psychopathology in schizophrenia. The PANSS is a formal interview, from which 30 symptoms are rated along a 7 point scale that ranges from 1 (absent) to 7 (extreme psychopathology). Schizophrenia symptom severity will be assessed with the PANSS and monitored to determine change in total, positive, negative, cognitive or general psychopathology symptoms.
Measured: At screening visit and at three monitoring visits (week 4, week 8, week 12)
Secondary outcomes (2)
The Montgomery Åsberg Depression Rating Scale (MADRS)
The MADRS is a 10 item semi-structured clinician-rated interview of depression where each item (depression symptom) is rated of a 7 point scale ranging from 0 to 6. The MADRS will be used to monitor the participant's experience of depressive symptoms and severity across the trial.
Measured: At baseline visit and at three monitoring visits (week 4, week 8, week 12)
Blood Test= C-Reactive Protein (CRP)
CRP to determine changes in baseline levels in systemic and central nervous system inflammation)
Measured: Screening visit and monitoring visit (week 12)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2010 (estimated)
- Study startJul 2010
- Primary completionAug 2018
- Study completionAug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Schizoaffective and Schizophreniform DisordersStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayside Health
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Professor Jayashri Kulkarni, Principal investigator, Monash Alfred Psychiatry Research Centre (MAPrc)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01121042
- Sponsor's protocol ID
- 145/10
- Status last verified
- Oct 2020
- First submitted
- 9 May 2010
- Last updated
- 14 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Kulkarni J, Thomas N, Hudaib AR, Gavrilidis E, Gurvich C. Ondansetron - a promising adjunctive treatment for persistent schizophrenia. J Psychopharmacol. 2018 Nov;32(11):1204-1211. doi: 10.1177/0269881118798608. Epub 2018 Oct 25.
PubMed 30359166
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double Blind, Placebo-Controlled, Randomised Investigation of Ondansetron in Schizophrenia
- ClinicalTrials.gov ID
- NCT01121042
- Acronym / sponsor ID
- 145/10
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Bayside HealthOther government
- Study start
- Jul 2010
- Primary completion
- Aug 2018 (actual)
- Study completion
- Aug 2018 (actual)
- First posted
- 12 May 2010 (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 evaluate the overall effectiveness of Ondansetron as an adjunctive or "add-on" medication in the treatment of Schizophrenia. This study is a double blind, placebo-controlled, randomised, 12 week trial.
Detailed description
Ondansetron is a medication currently approved by the Australian Therapeutic Goods Administration for the treatment of drug-induced vomiting and nausea. Beyond this traditional use there have been several case reports and small clinical trials advocating the use of Ondansetron in the treatment of adult Schizophrenia. Overall these studies lend support to the use of Ondansetron in conjunction with mainstream antipsychotic medication in improving not only the positive symptoms associated with Schizophrenia but also the 'hard to treat' negative and cognitive symptoms. Furthermore, Ondansetron may also have potential benefits in reducing the adverse motor effects (e.g. tremor, uncontrolled muscle movements) associated with the use of many antipsychotic medications.
60 participants aged 18-65 inclusive with a DSM-IV diagnosis of Schizophrenia, Schizoaffective, or Schizophreniform disorder will be recruited. This study proposes to conduct a randomized, controlled treatment trial to investigate the efficacy of ondansetron as an adjunctive treatment in reducing negative and positive symptoms plus improving cognitive symptoms. There will be an initial screening session to determine participant suitability, a baseline session where the study medication (Ondansetron or Placebo) will be dispensed, followed by three monitoring visits.
The efficacy of Ondansetron will be evaluated by the following instruments:
- Positive and Negative Symptom Scale (PANSS)
- Montgomery-Åsberg Depression Rating Scale (MADRS)
- C-Reactive protein (marker of systematic and brain specific inflammation)
Safety will be assessed through adverse event reporting using the Adverse symptom Checklist (ASC), blood analysis, urinalysis, a 12-lead Electrocardiogram (ECG) and a physical examination. Adverse motor symptoms will also be assessed by the Abnormal Involuntary Movement Scale and the Simpson-Angus Scale. In addition a safety and monitoring committee consisting of research and medical staff external to the project will regularly review adverse events.
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 |
|---|---|---|
| Ondansetron | Active comparator | Drug: OndansetronOndansetron oral capsule 8mg daily |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo (100% lactose) matched oral capsule |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Aged between 18-65 years of age
- Have a current DSM-IV-TR diagnosis of schizophrenia, schizoaffective of schizophreniform disorders (diagnosis will be confirmed using the MINI Neuropsychiatric Interview)
- Have been treated with a stable and standard dose (as determined by the PORT Treatment Recommendations for schizophrenia [33]) of an atypical antipsychotic agent (not including amisulpride owing to its 5HT3 actions) as their primary antipsychotic treatment for a minimum of eight weeks before entry into the trial
- Are experiencing positive symptoms as evidenced by a score of >15 on the Positive Syndrome Subscale of the PANSS, and/or negative psychotic symptoms as evidenced by a score of >15 on the Negative Syndrome Subscale of the PANSS and /or significant cognitive dysfunction, as evidenced by at least 15 on the cognitive subscale. The cognition subscale used in this study, which included items of G10, G11, G12, P2, N5, and N7 from the PANSS were generated from previous studies.
- Have a level of understanding sufficient to provide informed consent and to communicate with the investigators, study coordinator, and site personnel.
Key exclusion criteria (4 listed)
- Have an unstable medical condition, neurological disorder or an unstable seizure disorder. Any clinical significant electrocardiogram (ECG) abnormality at screening, including sinus bradycardia (ersting heart rate <50 beats per minute), atrial fibrillation, 2nd or 3rd degree AV block (AVB), prolonged ATc (QTcF>450ms in males or >470ms in females) history of congenital long AT syndromes, or risk of Torsades de Pointes because of family history of sudden death.
- Currently pregnant or breastfeeding
- Have a current DSM-IV-TR diagnosis of substance abuse or dependence disorder, or another Axis I disorder
- Regularly use of another 5HT3 antagonist such as metoclopramide, cocaine, tropisetron, granisetron, palonosetron
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 |
|---|---|---|
| Ondansetron8mg per day oral capsule | Drug | Ondansetron |
| Placebodaily oral capsule matched to active study medication. Made form 100% lactose powder | Drug | Placebo |
Primary outcome
Positive and Negative Symptom Scale (PANSS)
Time frame: At screening visit and at three monitoring visits (week 4, week 8, week 12)
The PANSS is a widely used, drug-sensitive, valid and reliable measure of psychopathology in schizophrenia. The PANSS is a formal interview, from which 30 symptoms are rated along a 7 point scale that ranges from 1 (absent) to 7 (extreme psychopathology). Schizophrenia symptom severity will be assessed with the PANSS and monitored to determine change in total, positive, negative, cognitive or general psychopathology symptoms.
2 secondary outcomes
The Montgomery Åsberg Depression Rating Scale (MADRS)
Time frame: At baseline visit and at three monitoring visits (week 4, week 8, week 12)
Blood Test= C-Reactive Protein (CRP)
Time frame: Screening visit and monitoring visit (week 12)
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 14 Oct 2020.
- Derived from this study: PubMed 30359166Kulkarni J, Thomas N, Hudaib AR, Gavrilidis E, Gurvich C. Ondansetron - a promising adjunctive treatment for persistent schizophrenia. J Psychopharmacol. 2018 Nov;32(11):1204-1211. doi: 10.1177/0269881118798608. Epub 2018 Oct 25.
- Monash Alfred Psychiatry Research Centre (MAPrc) websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Professor Jayashri Kulkarni principal investigator
Monash Alfred Psychiatry Research Centre (MAPrc)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ondansetron in people with Schizoaffective and Schizophreniform Disorders and Schizophrenia, run by Bayside Health at 1 site in Australia.
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 5 inclusion and 4 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 14 Oct 2020. 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 Australia. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Positive and Negative Symptom Scale (PANSS) (time frame: At screening visit and at three monitoring visits (week 4, week 8, week 12)). 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 NCT01121042, which also lists 1 linked publication.
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 14 Oct 2020.