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Randomized Double Blind Placebo Control Study in Patients With Schizophrenia (ROSES)

This study has been completed.
Sponsor:
Collaborators:
Stanley Medical Research Institute
Dow University of Health Sciences
Karwan e Hayat
Abbasi Shaheed Hospital
Information provided by (Responsible Party):
Pakistan Institute of Learning and Living
ClinicalTrials.gov Identifier:
NCT01602029
First received: May 17, 2012
Last updated: November 8, 2014
Last verified: May 2012
  Purpose

Negative symptoms and cognitive deficits are two partially-related features of schizophrenia which have a major negative impact on social function and objective quality of life. Standard drug treatments have little impact on either and arguably no effect on primary negative symptoms. Social dysfunction has major economic consequences in both the developed and developing world. There is evidence that anti-inflammatory treatment may have beneficial effects in patients with schizophrenia.


Condition Intervention Phase
Schizophrenia
Schizoaffective Disorder
Psychosis Not Otherwise Specified
Schizophreniform Disorder
Drug: Ondansetron
Drug: Simvastatin
Drug: Placebo
Drug: Odansetron plus simvastatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Double Blind Placebo Controlled Study of Ondansetron and Simvastatis Added to Treatment as Usual in Patients With Schizophrenia

Resource links provided by NLM:


Further study details as provided by Pakistan Institute of Learning and Living:

Primary Outcome Measures:
  • Negative symptom severity [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Negative symptom severity as defined by negative syndrome subscale score on the Positive and Negative Syndrome Scale


Secondary Outcome Measures:
  • cognitive functioning [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    1. Full PANSS and positive syndrome subscale score
    2. Clinical Global Impression
    3. Functional outcome


Enrollment: 303
Study Start Date: August 2010
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ondansetron
ondansetron added to TAU Ondansetron will be administered in 8mg once daily dose
Drug: Ondansetron
ondansetron added to TAU Ondansetron will be administered in 8mg once daily dose
Active Comparator: Simvastatin
Simvastatin added to TAU Simvastatin 20mg taken as once daily dose
Drug: Simvastatin
Simvastatin added to TAU Simvastatin 20mg taken as once daily dose
Placebo Comparator: Placebo
Placebo added to TAU
Drug: Placebo
Placebo added to TAU
Active Comparator: Odansetron Plus Simvastatin
Ondansetron will be administered in 8mg once daily dose and Simvastatin 20mg taken as once daily dose
Drug: Odansetron plus simvastatin
Ondansetron will be administered in 8mg once daily dose and Simvastatin 20mg taken as once daily dose

Detailed Description:

Negative symptoms and cognitive deficits are two partially-related features of schizophrenia which have a major negative impact on social function and objective quality of life. Evidence indicates that anti-inflammatory treatment may have beneficial effects in schizophrenia. From our preliminary randomised double-blind placebo-controlled clinical trial in Pakistan and Brazil, it is indicated that addition of minocycline (an antibiotic and anti-inflammatory drug) for one year to treatment as usual (TAU) reduced negative symptoms and improved some cognitive measures (Chaudhry et al 2009).

Statins are primarily HMG-CoA reductase inhibitors also anti-inflammatory agents and known to decrease C-reactive protein (CRP). Higher levels of CRP (>0.50 mg/dl) are associated with marked negative symptoms and higher total PANSS scores in patients with schizophrenia. (Fan et al 2007)

Ondansetron, a selective 5-hydroxytryptamine-3 antagonist, is quite commonly used as an antiemetic in cancer patients (Marty et al 1990). There are several small trials suggesting that ondansetron as an adjunct to antipsychotics is effective in improving negative symptoms and memory in patients suffering from schizophrenia (Ahkonzadeh et al 2009, Levkovitz et al 2005 and Zhang et al 2006).

The Primary objective of this study is addition of ondansetron and /or simvastatin to TAU for patients with schizophrenia will result in improvement in negative symptoms

The Secondary objectives include:

  • improvement in positive or other symptoms
  • social functioning
  • cognitive functions
  • additive effects of ondansetron and simvastatin
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Patients aged 18 to 65 years
  2. Patients will be recruited both from inpatients and outpatients.
  3. Diagnostic and Statistical Manual-IV (DSM-IV TR) diagnosis of schizophrenia, schizoaffective disorder, psychosis not otherwise specified or schizophreniform disorder
  4. Competent and willing to give informed consent
  5. Stable on medication 4 weeks prior to baseline
  6. No planned medication change
  7. Able to take oral medication and likely to complete the required evaluations
  8. Female participants of child bearing age must be willing to use adequate contraceptives for the duration of the study, and, willing to have a pregnancy test pre treatment and at ten weekly intervals while on study medication,
  9. Not planning to relocate in the next 12 months

Exclusion Criteria

  1. Relevant ICD 10 organic brain disease or neurological diagnoses (including ECG conduction abnormalities, neurological disorder, or an active seizure)
  2. Subjects who will meet the criteria for a DSM-IV TR diagnosis of alcohol or substance abuse (other than for nicotine) within the last month or the criteria for DSM-IV TR alcohol or substance dependence (other than for nicotine) within the last 6 months
  3. Any change of psychotropic medications within the previous 4 weeks
  4. Pregnant or lactating women and those of reproductive age without adequate contraception
  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: NCT01602029

Locations
Pakistan
Abbasi Shaheed Hospital
Karachi, Sindh, Pakistan
Dow university of Health Sciences
Karachi, Sind, Pakistan
Karwan e hayat
Karachi, Pakistan
Sponsors and Collaborators
Pakistan Institute of Learning and Living
Stanley Medical Research Institute
Dow University of Health Sciences
Karwan e Hayat
Abbasi Shaheed Hospital
Investigators
Principal Investigator: Imran Chaudhry, MD University of Manchester
  More Information

Additional Information:
No publications provided by Pakistan Institute of Learning and Living

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pakistan Institute of Learning and Living
ClinicalTrials.gov Identifier: NCT01602029     History of Changes
Other Study ID Numbers: roses_pill
Study First Received: May 17, 2012
Last Updated: November 8, 2014
Health Authority: Pakistan: Research Ethics Committee

Keywords provided by Pakistan Institute of Learning and Living:
Anti inflammatory
Schizophrenia
Simvastatin
Ondansetron

Additional relevant MeSH terms:
Disease
Psychotic Disorders
Schizophrenia
Mental Disorders
Pathologic Processes
Schizophrenia and Disorders with Psychotic Features
Ondansetron
Simvastatin
Anti-Anxiety Agents
Anticholesteremic Agents
Antiemetics
Antimetabolites
Antipruritics
Antipsychotic Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Depressants
Dermatologic Agents
Enzyme Inhibitors
Gastrointestinal Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents

ClinicalTrials.gov processed this record on November 20, 2014