Double Blind, Placebo-Controlled, Randomised Investigation of Ondansetron in Schizophrenia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01121042
Recruitment Status : Unknown
Verified March 2016 by Bayside Health.
Recruitment status was:  Recruiting
First Posted : May 12, 2010
Last Update Posted : March 2, 2016
Information provided by (Responsible Party):
Bayside Health

Brief 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.

Condition or disease Intervention/treatment Phase
Schizoaffective and Schizophreniform Disorders Schizophrenia Drug: Ondansetron Drug: Placebo Phase 3

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double Blind, Placebo-Controlled, Randomised Investigation of Ondansetron in Schizophrenia
Study Start Date : July 2010
Estimated Primary Completion Date : June 2016
Estimated Study Completion Date : June 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Ondansetron
Ondansetron oral capsule 8mg daily
Drug: Ondansetron
8mg per day oral capsule
Placebo Comparator: Placebo
Placebo (100% lactose) matched oral capsule
Drug: Placebo
daily oral capsule matched to active study medication. Made form 100% lactose powder

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. The Montgomery Åsberg Depression Rating Scale (MADRS) [ Time Frame: At baseline visit and at three monitoring visits (week 4, week 8, week 12) ]
    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.

  2. Blood Test= C-Reactive Protein (CRP) [ Time Frame: Screening visit and monitoring visit (week 12) ]
    CRP to determine changes in baseline levels in systemic and central nervous system inflammation)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Aged between 18-65 years of age
  2. Have a current DSM-IV-TR diagnosis of schizophrenia, schizoaffective of schizophreniform disorders (diagnosis will be confirmed using the MINI Neuropsychiatric Interview)
  3. 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
  4. 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.
  5. Have a level of understanding sufficient to provide informed consent and to communicate with the investigators, study coordinator, and site personnel.

Exclusion Criteria:

  1. 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.
  2. Currently pregnant or breastfeeding
  3. Have a current DSM-IV-TR diagnosis of substance abuse or dependence disorder, or another Axis I disorder
  4. Regularly use of another 5HT3 antagonist such as metoclopramide, cocaine, tropisetron, granisetron, palonosetron

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01121042

Contact: Jayashri Kulkarni, MBBS,MPM,FRANZCP,PhD +61 3 9076 6924
Contact: Anthony deCastella, Dip App Sci, BA, MA +61 3 9076 6554 ext 66554

Australia, Victoria
Monash Alfred Psychiatry Research Centre (MAPrc) Recruiting
Melbourne, Victoria, Australia, 3004
Contact: Jayashri Kulkarni, MBBS,MPM,FRANZCP,PhD    +61 3 9076 6924   
Contact: Anthony deCastella, Dip AppSci,BA,MA    +61 3 9076 6554   
Principal Investigator: Professor Jayashri Kulkarni         
Sponsors and Collaborators
Bayside Health
Principal Investigator: Professor Jayashri Kulkarni Monash Alfred Psychiatry Research Centre (MAPrc)

Additional Information:
Responsible Party: Bayside Health Identifier: NCT01121042     History of Changes
Other Study ID Numbers: 145/10
First Posted: May 12, 2010    Key Record Dates
Last Update Posted: March 2, 2016
Last Verified: March 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Psychotic Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Dermatologic Agents
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Anti-Anxiety Agents