Curcumin as a Novel Treatment to Improve Cognitive Dysfunction in Schizophrenia

Schizophrenia Clinical Trial

Official title:

Curcumin as a Novel Treatment to Improve Cognitive Dysfunction in Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02104752
• Other study ID #: 2013-121701
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 2014
• Est. completion date: October 2017

Study information

• Verified date: April 2019
• Source: VA Greater Los Angeles Healthcare System
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: October 2017
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Cognition
• Cognitive Dysfunction
• Mental Disorders
• Psychosis
• Psychotic Disorders
• Schizophrenia

Intervention

Drug:
• Curcumin
360 mg/day (divided into twice daily oral doses)
• Placebo
Inactive, matched placebo ("Sugar Pill")

Locations

Country	Name	City	State
United States	VA Greater Los Angeles	Los Angeles	California

Sponsors (4)

Lead Sponsor	Collaborator
VA Greater Los Angeles Healthcare System	Stanley Medical Research Institute, Theravalues, Inc., University of California, Los Angeles

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB)	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.	Baseline, Week 4, Week 8
Secondary	Electroencephalogram (EEG) Mismatch Negativity Paradigm (MMN)	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.	Baseline, Week 4, Week 8
Secondary	Brain Derived Neurotrophic Factor (BDNF)	Serum will be collected at baseline, 4 weeks, and 8 weeks. BDNF concentrations will be quantified by enzyme-linked immunosorbent assay.	Baseline, Week 4, Week 8
Secondary	Brief Psychiatric Rating Scale (BPRS)	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).	Baseline, Week 4, Week 8
Secondary	The Clinical Assessment Interview for Negative Symptoms (CAINS)	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).	Baseline, Week 4, Week 8