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

Pakistan Institute of Living and Learning

Status and phase: Completed; Phase 2

Conditions: Schizophreniform Disorder; Psychosis Not Otherwise Specified; Schizophrenia; Schizoaffective Disorder

Treatments: Drug: Odansetron plus simvastatin; Drug: Placebo; Drug: Simvastatin; Drug: Ondansetron

Study type: Interventional

Funder types: Other

Identifiers

NCT01602029

roses_pill

Details and patient eligibility

About

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.

Full 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

Enrollment: 303 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

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303 participants in 4 patient groups, including a placebo group

Ondansetron

Active Comparator group

Description:

ondansetron added to TAU Ondansetron will be administered in 8mg once daily dose

Treatment:

Drug: Ondansetron

Simvastatin

Active Comparator group

Description:

Simvastatin added to TAU Simvastatin 20mg taken as once daily dose

Treatment:

Drug: Simvastatin

Placebo

Placebo Comparator group

Description:

Placebo added to TAU

Treatment:

Drug: Placebo

Odansetron Plus Simvastatin

Active Comparator group

Description:

Ondansetron will be administered in 8mg once daily dose and Simvastatin 20mg taken as once daily dose

Treatment:

Drug: Odansetron plus simvastatin