Anti-Inflammatory Treatment of Schizophrenia

NCT01514682 | Completed Results DMC

• 1 other identifier: HP-00051603; 11T-002
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Despite current antipsychotic treatment, the majority of people with schizophrenia continue to exhibit persistent positive and negative symptoms and cognitive impairments. An alternative approach to the use of psychotropic agents for the treatment of persistent symptoms is the use of anti-inflammatory agents to reverse the pro-inflammatory state hypothesized to underlie the symptom and sign manifestations of the illness. The investigators primary hypothesis is that add-on anti-inflammatory combination therapy will have significant beneficial effects on persistent positive symptoms and cognitive impairments. The investigators secondary hypotheses are:

1. 1.add-on anti-inflammatory combination therapy will be associated with improvements in depressive and negative symptoms and a reduction in pro-inflammatory cytokines
2. 2.add-on anti-inflammatory combination therapy compared to placebo will not be associated with elevated adverse risk.

Conditions

Schizophrenia

Keywords

schizophrenia; anti-inflammatory; salsalate; statins; omega-3-fatty acids

Outcome Measures

Primary Outcomes (2)

• Change in Persistent Positive Symptoms

  The Brief Psychiatric Rating Scale (BPRS) positive symptom items are: conceptual disorganization, hallucinatory behavior, unusual thought content, and suspiciousness. The total score is calculated by adding the scores for each item. Each scale ranges from "1=Not Present" to "7=Very Severe". The minimum score is 4 and the maximum score is 28. A higher score indicates a more severe positive symptom rating.

  The BPRS will be administered at baseline and every two weeks throughout the double-blind phase of the study, for up to 12 weeks.

• Change in Neuropsychological Test Performance

  The MATRICS Consensus Cognitive Battery (MCCB) composite score by week ranging from -10-100 with a higher score indicating a better outcome.

  The MCCB was administered at baseline and end-of-study (Week 12).

Secondary Outcomes (4)

• Change in Depressive Symptoms

  The CDS was administered at baseline and every two weeks throughout the double-blind phase of the study, for up to 12 weeks.

• Change in Negative Symptoms

  Baseline and every two weeks throughout the double-blind phase of the study, for up to 12 weeks.

• Change in Pro-inflammatory Cytokines

  A cytokine profile will be collected at baseline and at week 12 (end-of-study).

• Change in C-Reactive Protein (CRP)

  A cytokine profile will be collected at baseline and at week 12 (end-of-study).

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo pills to be assigned using a permuted randomization system

Drug: Placebo

Anti-inflammatory Combination Therapy

EXPERIMENTAL

Salsalate, statin and omega-3-fatty acid combination therapy

Drug: Anti-inflammatory Combination Therapy

Interventions

Anti-inflammatory Combination Therapy DRUG

1. salsalate: target dose 4 gm/day, administered in two divided doses of 2 gm in the morning and 2 gm in the evening 2. fluvastatin: target dose 40 mg/day, administered in a single evening dose 3. combined omega-3-fatty acid preparation of EPA and DHA; target dose EPA 2 gm/day and DHA 2 gm/day administered in a single evening dose

Anti-inflammatory Combination Therapy

Placebo DRUG

Non-medication pills; To be taken in morning and evening intervals.

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants will meet DSM-IV-TR criteria for schizophrenia or schizoaffective disorder.
• Participants will be required to meet the following symptom criteria:
• BPRS total score of 45 or greater on the 18 item version (scale: 1-7) or a Clinical Global Impression (CGI) severity of illness item score of 4 (moderate) or greater.
• BPRS positive symptom item total score of 8 or greater and a score of 4 or more on at least one individual item.
• Participants will be clinically stable, be treated with the same antipsychotic for at least 60 days and a constant therapeutic dose for at least 30 days prior to study entry.
• Participants must be judged competent to participate in the informed consent process and provide voluntary informed consent

You may not qualify if:

• Participants who meet DSM-IV-TR criteria for alcohol or substance dependence (except nicotine) within the last 6 months or DSM-IV-TR criteria for alcohol or substance abuse (except nicotine) within the last month will be excluded
• Participants with a current infection or an organic brain disorder or medical condition, whose pathology or treatment could alter the presentation or treatment of schizophrenia or significantly increase the risk associated with the proposed treatment protocol will be excluded.
• Participants with a history of: aspirin allergy, pre-existing tinnitus, tuberculosis, HIV, or hepatitis C; or autoimmune disease.
• Participants who are currently treated with a statin, warfarin, dipyridamole, or other anti-coagulants.
• Participant is currently treated with an omega-3-fatty acid preparation and cannot discontinue their use of the preparation for the duration of the study.
• Female participant who is sexually active and not using any form of birth control such as oral contraceptives or IUDs.
• Female participant who is pregnant or breastfeeding.
• Participant with current/active peptic ulcer disease or gastritis; anemia or thrombocytopenia (platelet count ≤120).
• Participant who is currently treated with a medication that can increase the risk of myopathy and rhabdomyolysis such as Fluconazole, Ketoconazole, Colchicine, Daptomycin, Erythromycin, or immunosuppressants that alter statin levels.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

Maryland Psychiatric Research Center

Baltimore, Maryland, 21228, United States

Location

Related Publications (1)

• Buchanan RW, Weiner E, Kelly DL, Gold JM, Chen S, Zaranski J, Blatt F, Wehring H, Carpenter WT. Anti-inflammatory Combination Therapy for the Treatment of Schizophrenia. J Clin Psychopharmacol. 2020 Sep/Oct;40(5):444-450. doi: 10.1097/JCP.0000000000001253.

  PMID: 32796391 DERIVED

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Robert W. Buchanan, M.D.
• Organization: Maryland Psychiatric Research Center

rbuchanan@som.umaryland.edu

410-402-7876

Study Officials

• Robert W Buchanan, MD

  Maryland Psychiatric Research Center, University of Maryland School of Medicine

  PRINCIPAL INVESTIGATOR

• William T Carpenter, MD

  Maryland Psychiatric Research Center, University of Maryland School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Maryland Psychiatric Research Center, Outpatient Research Program

Study Record Dates

• First Submitted: January 12, 2012
• First Posted: January 23, 2012
• Study Start: June 1, 2012
• Primary Completion: April 17, 2017
• Study Completion: April 17, 2017
• Last Updated: March 3, 2022
• Results First Posted: March 29, 2018

Record last verified: 2022-03

Locations

US (1)