Role of Anti-Inflammatory Agents in Patients With Schizophrenia

NCT00929955 | Completed Phase 1

• 1 other identifier: PILL-UoM-0110
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

Anti inflammatory; Schizophrenia; Simvastatin; ondansetron

Outcome Measures

Primary Outcomes (1)

• acceptability and tolerability of simvastatin and ondansetron added to TAU

  3 months

Secondary Outcomes (3)

• 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

Study Arms (3)

Ondansetron

ACTIVE COMPARATOR

Drug: Ondansetron

Simvastatin

ACTIVE COMPARATOR

Drug: Simvastatin

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Ondansetron DRUG

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

Ondansetron

Simvastatin DRUG

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

Simvastatin

Placebo DRUG

Placebo added to TAU

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pakistan Institute of Living and Learning: lead
• Karwan e Hayat: collaborator
• Dow University of Health Sciences: collaborator

Study Sites (2)

Dow University of Health Sciences

Karachi, Pakistan

Location

Karwan e hayat

Karachi, Pakistan

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Ondansetron; Simvastatin

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Imran B Chaudhry, MD

  University of Manchester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 28, 2009
• First Posted: June 30, 2009
• Study Start: June 1, 2009
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2010
• Last Updated: August 5, 2019

Record last verified: 2019-08

Locations

PA (2)