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

Condition(s) targeted: Schizoaffective and Schizophreniform Disorders; Schizophrenia

Intervention: Ondansetron (Drug); Placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Bayside Health

Official(s) and/or principal investigator(s):
Professor Jayashri Kulkarni, Principal Investigator, Affiliation: Monash Alfred Psychiatry Research Centre (MAPrc)

Overall contact:
Penny Weeks, Phone: 03 9076 6590, Email: penny.weeks@monash.edu

The aim of this study is to evaluate the overall effectiveness of Ondansetron as an adjunctive or "add-on" medication in the treatment of adult chronic and persistent Schizophrenia. This study is a double blind, placebo-controlled, randomised, 12 week trial.

Official title: Double Blind, Placebo-Controlled, Randomised Investigation of Ondansetron in Chronic Residual Schizophrenia

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Positive and Negative Symptom Scale (PANSS)

MATRICS Cognitive Consensus Battery (MCCB)

Secondary outcome:

The Montgomery Åsberg Depression Rating Scale (MADRS)

Lehman's Quality of Life Interview (QoLI)

Blood Test= C-Reactive Protein (CRP)

Mini International Neuropsychiatric Interview (M.I.N.I)

Wechsler Test of Adult Reading (WTAR)

The Abnormal Involuntary Movement Scale (AIMS)

The Simpson-Angus Scale (SAS)

The Adverse Symptom Checklist (ASC)

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.

160 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 large-scale, randomized, controlled treatment trial to investigate the efficacy of ondansetron as an adjunctive treatment in reducing negative and 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)

- MATRICS Cognitive Consensus Battery (MCCB)

- Lehman's Quality of Life Questionnaire

- Montgomery-Åsberg Depression Rating Scale (MADRS)

- C-Reactive protein (marker of systematic and brain specific inflammation)

- Electroencephalogram (EEG)

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.

The overall study duration is three years with individual participation taking 12-13 weeks.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

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

Penny Weeks, Phone: 03 9076 6590, Email: penny.weeks@monash.edu

Monash Alfred Psychiatry Research Centre (MAPrc), Melbourne, Victoria 3004, Australia; Recruiting
Penny Weeks, BSc. (Hons) Psychophysiology, Phone: 03 9076 6590, Email: penny.weeks@monash.edu
Professor Jayashri Kulkarni, Principal Investigator

Monash Alfred Psychiatry Research Centre (MAPrc) website

Starting date: July 2010
Last updated: February 6, 2013