Role of Anti-Inflammatory Agents in Patients With Schizophrenia

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Pakistan
  • Karachi, Pakistan
    • Dow University of Health Sciences
  • Karachi, Pakistan
    • Karwan e Hayat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnostic and Statistical Manual-IV (DSM-IV) diagnosis of schizophrenia, schizoaffective disorder, psychosis not otherwise specified or schizophreniform disorder
2. competent and willing to give informed consent
3. stable on medication 4 weeks prior to baseline
4. able to take oral medication and likely to complete the required evaluations
5. 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:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
acceptability and tolerability of simvastatin and ondansetron added to TAU	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Pakistan Institute of Living and Learning
• Collaborators: Dow University of Health Sciences; Karwan e Hayat
• Investigators: Principal Investigator: Imran B Chaudhry, MD, University of Manchester

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2009
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: June 28, 2009
• First Submitted That Met QC Criteria: June 29, 2009
• First Posted (Estimate): June 30, 2009

Study Record Updates

• Last Update Posted (Actual): August 5, 2019
• Last Update Submitted That Met QC Criteria: August 2, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Schizophrenia; Simvastatin; Anti inflammatory; ondansetron
• 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: PILL-UoM-0110