Curcumin as a Novel Treatment to Improve Cognitive Dysfunction in Schizophrenia

Phase 1

Completed

Conditions: Schizophrenia
Cognition
Psychosis

Interventions: Drug: Placebo
Drug: Curcumin

Registration Number: NCT02104752

Lead Sponsor: VA Greater Los Angeles Healthcare System

Brief Summary: The investigators propose to test whether curcumin nanoparticles will improve behavioral measures and biomarkers of cognition and neuroplasticity in patients with schizophrenia who are already receiving a stable dose of antipsychotic.

Detailed Description: The investigators will use a formulation of curcumin with high bioavailability that possesses a pharmacokinetic profile expected to exert biological effects. Specifically, 36 subjects will be enrolled in the double-blind randomized controlled trial. They will be randomized to curcumin or placebo for 8 weeks. At baseline, and 4 and 8 weeks, subjects will receive assessments of neurocognition (e.g., processing speed, attention and vigilance, working memory, learning, reasoning and problem solving), social cognition, EEG biomarkers (e.g., visual cortical plasticity and mismatch negativity), a serum marker of neurogenesis (BDNF levels), and clinical symptoms (positive and negative symptoms). At weeks 2 and 6 subjects will return for additional safety (e.g., vitals, side effects, akathisia) and medication adherence assessments. Improvement on the primary outcome measure (MATRICS Consensus Cognitive Battery), as well as secondary outcome measures, will be compared between participants randomized to placebo versus curcumin. The results of this study will establish whether curcumin is a viable adjunctive agent for future larger clinical trials.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 39

Inclusion Criteria

DSM-5 diagnosis of schizophrenia
age 18 - 65 years
understand spoken English sufficiently to comprehend testing procedures
corrected vision of at least 20/30
currently prescribed an antipsychotic medication

Exclusion Criteria

clinically significant neurological disease determined by medical history (e.g., epilepsy)
history of serious head injury (i.e., loss of consciousness > 1 hr., no neuropsychological sequelae, no cognitive rehabilitation post head injury)
sedatives or benzodiazepines within 12 hrs of testing
any psychiatric hospitalization within 3 months prior to study participation
behaviors suggesting any potential danger to self or others within 6 months prior to study participation
antipsychotic dose change more than 50% over the 3 months prior to study participation
acute medical problems or untreated chronic medical conditions within 3 months prior to study participation

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sugar Pill	Placebo	Matched placebo, 2 capsules twice daily.
Curcumin	Curcumin	Curcumin capsules (Theracurmin formulation of curcumin nanoparticles). Subjects randomized to curcumin will receive 360 mg/day (divided into twice daily oral doses).

Primary Outcome Measures

Name	Time	Method
Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB)	Baseline, Week 4, Week 8	This battery was developed as part of the National Institute of Mental Health (NIMH) sponsored Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Initiative to assess cognition in clinical trials of cognition enhancing drugs. The MCCB comprises 10 tests that assess 7 cognitive domains (speed of processing, verbal memory, visual memory, working memory, reasoning and problem solving, attention/vigilance, and social cognition). The MCCB takes approximately 65 minutes to administer and provides age and gender-corrected normed T-scores, including a global composite score and cognitive domain scores. The range of T-scores is between 0 to 100 with a mean of 50. Higher scores indicate better overall cognitive functioning.

Secondary Outcome Measures

Name	Time	Method
Electroencephalogram (EEG) Mismatch Negativity Paradigm (MMN)	Baseline, Week 4, Week 8	A passive attention auditory oddball paradigm will be used to assess MMN. For MMN, difference waves generated by subtracting the standard from deviant event related potentials (ERP) will be analyzed. The specific electrodes used to examine each component will be chosen based on maximal activity seen by inspection of the topographical maps. More negative values indicate a larger (i.e., better) MMN response.
Brain Derived Neurotrophic Factor (BDNF)	Baseline, Week 4, Week 8	Serum will be collected at baseline, 4 weeks, and 8 weeks. BDNF concentrations will be quantified by enzyme-linked immunosorbent assay.
Brief Psychiatric Rating Scale (BPRS)	Baseline, Week 4, Week 8	The Brief Psychiatric Rating Scale (BPRS) will be the primary measure for assessing positive symptoms. We will be using the UCLA expanded 24-item version of the scale. The total score ranges from 24-168, with lower scores being better (i.e., less symptomatology).
The Clinical Assessment Interview for Negative Symptoms (CAINS)	Baseline, Week 4, Week 8	The Clinical Assessment Interview for Negative Symptoms (CAINS) will be used to assess negative symptoms. This scale is comprised of 9 items that rate motivation and pleasure symptoms and 4 items that rate expression symptoms. We are reporting the motivation subscale. The total score can range from 0-36 (summed over the 9 items), with lower scores being better (i.e., less symptomatology).