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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Bayside Health
Sponsor:
Information provided by (Responsible Party):
Bayside Health
ClinicalTrials.gov Identifier:
NCT01121042
First received: May 9, 2010
Last updated: February 6, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Schizoaffective and Schizophreniform Disorders
Schizophrenia
Drug: Ondansetron
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double Blind, Placebo-Controlled, Randomised Investigation of Ondansetron in Chronic Residual Schizophrenia

Resource links provided by NLM:


Further study details as provided by Bayside Health:

Primary Outcome Measures:
  • Positive and Negative Symptom Scale (PANSS) [ Time Frame: At screening visit and at three monitoring visits (week 4, week 8, week 12) ] [ Designated as safety issue: No ]
    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.

  • MATRICS Cognitive Consensus Battery (MCCB) [ Time Frame: At baseline visit and at one monitoring visit (week 12) ] [ Designated as safety issue: No ]
    The MCCB is an eight domain neurocognitive battery that was developed to provide a reliable and sensitive measure of cognitive abilities commonly impaired in schizophrenia. Specifically the MCCB was designed to be used in clinical trials of cognitive-enhancing drugs with schizophrenia. It assesses the speed of processing, attention, verbal learning, working memory, visual learning, reasoning and problem solving and emotional intelligence.


Secondary Outcome Measures:
  • The Montgomery Åsberg Depression Rating Scale (MADRS) [ Time Frame: At baseline visit and at three monitoring visits (week 4, week 8, week 12) ] [ Designated as safety issue: No ]
    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.

  • Lehman's Quality of Life Interview (QoLI) [ Time Frame: At baseline visit and at one monitoring visit (week 12) ] [ Designated as safety issue: No ]
    The QoLI is a clinician- administered questionnaire used to measure QOL. It consisting of 143 questions including yes/no responses, ratings of subjective well-being on a seven-point scale (from 1 = 'couldn't be worse' to 7 = 'couldn't be better', the midpoint 4='mixed, equally satisfied and dissatisfied'), Cantril's ladder, free-response questions, and background information. This measure was designed for use with psychiatric populations and covers key QOL domains including work, leisure, finance, living situation, safety, family relations, social relations and health.

  • Blood Test= C-Reactive Protein (CRP) [ Time Frame: Screening visit and monitoring visit (week 12) ] [ Designated as safety issue: No ]
    CRP to determine changes in baseline levels in systemic and central nervous system inflammation)

  • Mini International Neuropsychiatric Interview (M.I.N.I) [ Time Frame: Screening ] [ Designated as safety issue: No ]
    The M.I.N.I. is a short structured psychiatric interview that be used to confirm diagnosis of Schizophrenia and screen for other major axis 1 disorders.

  • Wechsler Test of Adult Reading (WTAR) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The WTAR is a brief task that requires the participant to read out 50 irregularly spelt words. This task provides an indication of intellectual functioning by translating scores into equivalent WAIS-III (Wechsler Adult Intelligence Scale) intelligent quotient (IQ) scores. These scores will be used to ensure that intellectual functioning does not confound cognitive performance differences among participants.

  • The Abnormal Involuntary Movement Scale (AIMS) [ Time Frame: At screening visit and at three monitoring visits (week 4, week 8, week 12) ] [ Designated as safety issue: Yes ]
    The AIMS is a 12-item assessment tool that will be used to measure abnormal involuntary movements that may be associated with drug treatment

  • The Simpson-Angus Scale (SAS) [ Time Frame: At screening visit and at three monitoring visits (week 4, week 8, week 12) ] [ Designated as safety issue: Yes ]
    The SAS is a 10-item scale that will be used to assess the presence and severity of extrapyramidal side effects of medication.

  • The Adverse Symptom Checklist (ASC) [ Time Frame: At screening visit and at three monitoring visits (week 4, week 8, week 12) ] [ Designated as safety issue: Yes ]
    The ASC is a 21-item scale used to assess the presence and severity of adverse symptoms associated with antipsychotic treatments.


Estimated Enrollment: 160
Study Start Date: July 2010
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01121042

Contacts
Contact: Penny Weeks 03 9076 6590 penny.weeks@monash.edu
Contact: Alison Meeking 03 9076 6585 alison.meeking@monash.edu

Locations
Australia, Victoria
Monash Alfred Psychiatry Research Centre (MAPrc) Recruiting
Melbourne, Victoria, Australia, 3004
Contact: Penny Weeks, BSc. (Hons) Psychophysiology    03 9076 6590    penny.weeks@monash.edu   
Principal Investigator: Professor Jayashri Kulkarni         
Sponsors and Collaborators
Bayside Health
Investigators
Principal Investigator: Professor Jayashri Kulkarni Monash Alfred Psychiatry Research Centre (MAPrc)
  More Information

Additional Information:
No publications provided

Responsible Party: Bayside Health
ClinicalTrials.gov Identifier: NCT01121042     History of Changes
Other Study ID Numbers: 145/10
Study First Received: May 9, 2010
Last Updated: February 6, 2013
Health Authority: Australia: Human Research Ethics Committee

Additional relevant MeSH terms:
Psychotic Disorders
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Ondansetron
Anti-Anxiety Agents
Antiemetics
Antipruritics
Antipsychotic Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Depressants
Dermatologic Agents
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Antagonists
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on November 23, 2014