Curcumin as a Novel Treatment to Improve Cognitive Dysfunction in Schizophrenia

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02104752

Enrollment

Registered

2014-04-04

Start date

2014-07-31

Completion date

2017-10-31

Last updated

2019-05-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cognition, Psychosis, Schizophrenia

Keywords

Curcumin, Turmeric, Schizophrenia, Cognition, Psychosis

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.

Interventions

DRUGCurcumin

360 mg/day (divided into twice daily oral doses)

DRUGPlacebo

Inactive, matched placebo (Sugar Pill)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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).
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.
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).

Countries

United States

Participant flow

Participants by arm

Arm	Count
Curcumin Curcumin capsules (Theracurmin formulation of curcumin nanoparticles). Subjects randomized to curcumin will receive 360 mg/day (divided into twice daily oral doses). Curcumin: 360 mg/day (divided into twice daily oral doses)	17
Sugar Pill Matched placebo, 2 capsules twice daily. Placebo: Inactive, matched placebo (Sugar Pill)	19
Total	36

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Weight gain; unrelated anxiety	0	2
Overall Study	Withdrawal by Subject	1	0

Baseline characteristics

Characteristic	Curcumin	Sugar Pill	Total
Age, Continuous	50.1 years STANDARD_DEVIATION 9.6	50.9 years STANDARD_DEVIATION 10.6	50.5 years STANDARD_DEVIATION 10
Region of Enrollment United States	17 participants	19 participants	36 participants
Sex: Female, Male Female	6 Participants	0 Participants	6 Participants
Sex: Female, Male Male	11 Participants	19 Participants	30 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 17	0 / 19
serious Total, serious adverse events	0 / 17	0 / 19

Outcome results

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.