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

Randomized Double Blind Placebo Controlled Study of Ondansetron and Simvastatis Added to Treatment as Usual in Patients With Schizophrenia

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder; Psychosis Not Otherwise Specified
• Intervention / Treatment: Drug: Ondansetron; Drug: Simvastatin; Drug: Placebo; Drug: Odansetron plus simvastatin

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

• Study Type: Interventional
• Enrollment (Actual): 303
• Phase: Phase 2

Contacts and Locations

Study Locations

• Pakistan
  • Karachi, Pakistan
    • Karwan e hayat
  • Sind
    • Karachi, Sind, Pakistan
      • Dow University of Health Sciences
  • Sindh
    • Karachi, Sindh, Pakistan
      • Abbasi Shaheed Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Negative symptom severity	Negative symptom severity as defined by negative syndrome subscale score on the Positive and Negative Syndrome Scale	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cognitive functioning	Full PANSS and positive syndrome subscale score; Clinical Global Impression; Functional outcome	6 months

Collaborators and Investigators

• Sponsor: Pakistan Institute of Living and Learning
• Collaborators: Stanley Medical Research Institute; Dow University of Health Sciences; Abbasi Shaheed Hospital; Karwan e Hayat
• Investigators: Principal Investigator: Imran Chaudhry, MD, University of Manchester

Publications and helpful links

General Publications

• Chaudhry IB, Husain N, Husain MO, Hallak J, Drake R, Kazmi A, Rahman Ru, Hamirani MM, Kiran T, Mehmood N, Stirling J, Dunn G, Deakin B. Ondansetron and simvastatin added to treatment as usual in patients with schizophrenia: study protocol for a randomized controlled trial. Trials. 2013 Apr 17;14:101. doi: 10.1186/1745-6215-14-101.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: May 17, 2012
• First Submitted That Met QC Criteria: May 17, 2012
• First Posted (Estimate): May 18, 2012

Study Record Updates

• Last Update Posted (Estimate): November 11, 2014
• Last Update Submitted That Met QC Criteria: November 8, 2014
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: Schizophrenia; Ondansetron; Simvastatin; Anti inflammatory
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Disease; Psychotic Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antimetabolites; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antipruritics; Simvastatin; Ondansetron
• Other Study ID Numbers: roses_pill