Role of Anti-Inflammatory Agents in Patients With Schizophrenia

Sponsor

Pakistan Institute of Living and Learning (Other)

Overall Status

Completed

CT.gov ID

NCT00929955

Collaborator

Karwan e Hayat (Other), Dow University of Health Sciences (Other)

Enrollment

Locations

Arms

Actual Duration (Months)

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

There is some evidence that anti-inflammatory treatment may have beneficial effects in schizophrenia and major depression. Cox-2 inhibitors have been tested in preliminary clinical trials for schizophrenia and depression, showing favourable effects compared to placebo (Muller and Schwarz et al 2009).

Statins were introduced as cholesterol-lowering agents but have found much wider usage. They are anti-inflammatory agents and thus similar to the Cox-2 inhibitors, which have shown some ability as adjuncts to improve the symptoms of schizophrenia in preliminary studies. The statins are also known to decrease C-reactive protein (CRP), which has been shown in an SMRI-funded study to be elevated in a study of individuals with schizophrenia. Fan et al (2007) demonstrated in a small study in patients with schizophrenia that higher than normal levels of CRP (>0.50 mg/dl) was associated with marked negative symptoms and higher total PANSS scores.

Ondansetron is a serotonin (5-HT3) receptor antagonist that is generic and widely used to prevent nausea and vomiting in patients receiving chemotherapy for cancer. GSK did a small study on it as an antipsychotic in the 1980s. Since then, several small studies have suggested that it is effective as an adjunct drug in improving the symptoms of schizophrenia.

Statins are widely used in schizophrenia sufferers, particularly those taking second generation antipsychotics, to treat hypercholesterolemia. Both drugs are well tolerated and their side effect profiles well understood.

We propose to conduct a feasibility study in patients with chronic schizophrenia to explore the adjunct use of simvastatin and ondansetron on positive, negative and general psychopathology in comparisons to treatment as usual (TAU) over a 12 week period.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia Schizoaffective Disorder Psychosis Not Otherwise Specified Schizophreniform Disorder	Drug: Ondansetron Drug: Simvastatin Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Investigator)

Primary Purpose:

Treatment

Official Title:

Study of Role of Anti-Inflammatory Agents in Patients With Schizophrenia

Actual Study Start Date :

Jun 1, 2009

Actual Primary Completion Date :

Sep 1, 2009

Actual Study Completion Date :

Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ondansetron	Drug: Ondansetron ondansetron added to TAU Ondansetron will be administered in 8mg once daily dose
Active Comparator: Simvastatin	Drug: Simvastatin Simvastatin added to TAU Simvastatin 20mg taken as once daily dose
Placebo Comparator: Placebo	Drug: Placebo Placebo added to TAU

Arm

Intervention/Treatment

Active Comparator: Ondansetron

Drug: Ondansetron

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

Active Comparator: Simvastatin

Drug: Simvastatin

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

Placebo Comparator: Placebo

Drug: Placebo

Placebo added to TAU

Outcome Measures

Primary Outcome Measures

acceptability and tolerability of simvastatin and ondansetron added to TAU [3 months]

Secondary Outcome Measures

simvastatin and ondansetron added to TAU prevents the accumulation of negative symptoms in patients with schizophrenia [3 months]
simvastatin and ondansetron added to TAU prevents cognitive decline [3 months]
To compare the effect size [3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnostic and Statistical Manual-IV (DSM-IV) diagnosis of schizophrenia, schizoaffective disorder, psychosis not otherwise specified or schizophreniform disorder
competent and willing to give informed consent
stable on medication 4 weeks prior to baseline
able to take oral medication and likely to complete the required evaluations
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.

Exclusion Criteria:

Relevant medical illness [renal and hepatic] in the opinion of the investigators
history of high alcohol intake
any change of psychotropic medications within the previous six weeks
diagnosis of substance abuse (except nicotine or caffeine) or dependence within the last three months according to DSM-IV criteria
pregnant or breast-feeding.