Clinical trial NCT01602029: Randomized Double Blind Placebo Control Study in Patients with Schizophrenia
Official title: Randomized Double Blind Placebo Controlled Study of Ondansetron and Simvastatis Added to Treatment As Usual in Patients with Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Schizoaffective Disorder
Psychosis Not Otherwise Specified
Schizophreniform Disorder
Keywords: Anti inflammatory
Schizophrenia
Simvastatin
Ondansetron
Lead sponsor: Pakistan Institute of Living and Learning
Sponsor class: OTHER
Collaborators: name: Stanley Medical Research Institute
name: Dow University of Health Sciences
name: Abbasi Shaheed Hospital
First posted: 2012-05-18
Enrollment: 303
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Negative symptom severity
timeFrame: 6 months
Secondary outcomes:
measure: cognitive functioning
timeFrame: 6 months
Other outcomes:
Locations:
city: Karachi
country: Pakistan
facility: Abbasi Shaheed Hospital
state: Sindh
city: Karachi
country: Pakistan
facility: Dow university of Health Sciences
state: Sind
city: Karachi
country: Pakistan
facility: Karwan e hayat
Study officials:
affiliation: University of Manchester
name: Imran Chaudhry, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.