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

October 10, 2020 updated by: Bayside Health
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

85

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Melbourne, Victoria, Australia, 3004
        • Monash Alfred Psychiatry Research Centre (MAPrc)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
At screening visit and at three monitoring visits (week 4, week 8, week 12)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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)
CRP to determine changes in baseline levels in systemic and central nervous system inflammation)
Screening visit and monitoring visit (week 12)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bayside Health

Investigators

  • Principal Investigator: Professor Jayashri Kulkarni, Monash Alfred Psychiatry Research Centre (MAPrc)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2010

Primary Completion (ACTUAL)

August 1, 2018

Study Completion (ACTUAL)

August 1, 2018

Study Registration Dates

First Submitted

May 9, 2010

First Submitted That Met QC Criteria

May 9, 2010

First Posted (ESTIMATE)

May 12, 2010

Study Record Updates

Last Update Posted (ACTUAL)

October 14, 2020

Last Update Submitted That Met QC Criteria

October 10, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 145/10

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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