Clinical trial NCT02104752: Curcumin as a Novel Treatment to Improve Cognitive Dysfunction in Schizophrenia
Official title: Curcumin as a Novel Treatment to Improve Cognitive Dysfunction in Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Schizophrenia
Cognition
Psychosis
Keywords: Curcumin
Turmeric
Schizophrenia
Cognition
Psychosis
Lead sponsor: VA Greater Los Angeles Healthcare System
Sponsor class: FED
Collaborators: name: Stanley Medical Research Institute
name: Theravalues, Inc.
name: University of California, Los Angeles
First posted: 2014-04-04
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB)
timeFrame: Baseline, Week 4, Week 8
Secondary outcomes:
measure: Electroencephalogram (EEG) Mismatch Negativity Paradigm (MMN)
timeFrame: Baseline, Week 4, Week 8
measure: Brain Derived Neurotrophic Factor (BDNF)
timeFrame: Baseline, Week 4, Week 8
measure: Brief Psychiatric Rating Scale (BPRS)
timeFrame: Baseline, Week 4, Week 8
measure: The Clinical Assessment Interview for Negative Symptoms (CAINS)
timeFrame: Baseline, Week 4, Week 8
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: VA Greater Los Angeles
state: California
Study officials:
affiliation: VA Greater Los Angeles
name: Stephen R Marder, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: VA Greater Los Angeles
name: Jonathan K Wynn, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: VA Greater Los Angeles
name: Michael C Davis, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hurley LL, Akinfiresoye L, Nwulia E, Kamiya A, Kulkarni AA, Tizabi Y. Antidepressant-like effects of curcumin in WKY rat model of depression is associated with an increase in hippocampal BDNF. Behav Brain Res. 2013 Feb 15;239:27-30. doi: 10.1016/j.bbr.2012.10.049. Epub 2012 Nov 8.
citation: Dong S, Zeng Q, Mitchell ES, Xiu J, Duan Y, Li C, Tiwari JK, Hu Y, Cao X, Zhao Z. Curcumin enhances neurogenesis and cognition in aged rats: implications for transcriptional interactions related to growth and synaptic plasticity. PLoS One. 2012;7(2):e31211. doi: 10.1371/journal.pone.0031211. Epub 2012 Feb 16.
citation: Sasaki H, Sunagawa Y, Takahashi K, Imaizumi A, Fukuda H, Hashimoto T, Wada H, Katanasaka Y, Kakeya H, Fujita M, Hasegawa K, Morimoto T. Innovative preparation of curcumin for improved oral bioavailability. Biol Pharm Bull. 2011;34(5):660-5. doi: 10.1248/bpb.34.660.
citation: Shamsi S, Lau A, Lencz T, Burdick KE, DeRosse P, Brenner R, Lindenmayer JP, Malhotra AK. Cognitive and symptomatic predictors of functional disability in schizophrenia. Schizophr Res. 2011 Mar;126(1-3):257-64. doi: 10.1016/j.schres.2010.08.007. Epub 2010 Sep 15.
citation: Wynn JK, Green MF, Hellemann G, Karunaratne K, Davis MC, Marder SR. The effects of curcumin on brain-derived neurotrophic factor and cognition in schizophrenia: A randomized controlled study. Schizophr Res. 2018 May;195:572-573. doi: 10.1016/j.schres.2017.09.046. Epub 2017 Sep 29. No abstract available.