Sodium Butyrate For Improving Cognitive Function In Schizophrenia

Sodium Butyrate As A Treatment For Improving Cognitive Function In Schizophrenia

The purpose of this grant is to evaluate the efficacy of sodium butyrate as a novel treatment for cognitive deficits in schizophrenia (SZ). The aims will be to evaluate its effects on improving symptoms and functioning in SZ, and the relationship of the drug's clinical effects to epigenetic and inflammation related biochemical changes.

Study Overview

• Status: Withdrawn
• Conditions: Cognitive Impairment; Schizophrenic Disorder
• Intervention / Treatment: Drug: Sodium Butyrate; Drug: Placebo Oral Capsule

Detailed Description

The persistent cognitive deficits which can be appreciated across the course of SZ, from prodromal to chronic SZ, may be the most important underlying dysfunction in preventing functional, occupational, and social recovery in SZ compared to other symptom domains. Sodium butyrate is a short chain fatty acid and binds to the zinc site of histone deacetylases (HDAC). The inhibition of HDAC results in histone hyperacetylation. This study aims to evaluate its effects on improving symptoms and functioning in SZ, and the relationship of the drug's clinical effects to epigenetic and inflammation related biochemical changes.

The proposed study will be a double blind study of the effects of sodium butyrate on cognitive function and symptoms in chronic SZ patients showing continued cognitive deficits.The primary specific aims of the proposal will be to test the the MATRICS (MCCB) battery,delayed recall performance, and performance on real world functional tasks as assessed by the USCD Performance- Based Skills Assessment Battery (UPSA). In addition, we will also investigate whether sodium butyrate may improve other aspects of cognition.

We will also explore whether improvement in cognition is related to change in HDAC activity in peripheral blood cells and changes in inflammatory makers in the blood, and assess whether there is any improvement in psychopathology as measured by PANSS scale.

• Study Type: Interventional
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Shanghai Mental Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects who have cognitive deficits as indicated by a score of < 85 on RBANS,
2. meet criteria for DSM-5 diagnosis of chronic SZ, schizoaffective disorder (SA),
3. Subjects who are stably treated with antipsychotic medications and are not in acute exacerbation of illness symptoms.

Exclusion Criteria:

1. History of mental retardation or pervasive developmental disorder,
2. Subjects with a current serious neurological/CNS disorder (such as seizure disorder, stroke or multiple sclerosis) or brain trauma,
3. Current treatment with valproic acid, butyrate drugs, sulforaphane, or other drugs or chemicals known to have high HDAC inhibitory activity,
4. Pregnancy,
5. Severe unstable medical condition,
6. Current suicidal or homicidal thoughts,
7. Current alcohol or substance abuse (other than nicotine or occasional marijuana) in the last month.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sodium Butyrate; Dietary Supplement: Sodium Butyrate 4.38 gms of sodium butyrate per day for 12 weeks	Drug: Sodium Butyrate; Sodium butyrate is being supplied by T.E. Neesby (Brain White, T.E. Neesby, Inc.) in 730 mg capsules. The company asserts that their material is 98% pure and food grade. We will have identical placebo capsules. Subjects will receive 3 capsules twice daily (morning and late afternoon or evening) for a total of 4380 mg/day.
Placebo Comparator: Placebo Oral Capsule; Placebo Oral Capsule placebo capsules containing approximately 9 mg of sodium butyrate per day	Drug: Placebo Oral Capsule; Placebo Oral Capsule is also being supplied by T.E. Neesby (Brain White, T.E. Neesby, Inc.) and there is no difference from appearance, smell and taste. It contains 1.5 mg sodium butyrate per capsule. Subjects will receive 3 capsules twice daily (morning and late afternoon or evening) for a total of 9 mg/day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in MATRICS Battery Score	MATRICS Cognitive Battery	Basline, week 6, up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Logical Memory Test score	Logical Memory Test for longer term memory	Basline, up to 12 weeks
Change from baseline in Positive and Negative Syndrome Scale (PANSS) total score	Positive and Negative Syndrome Scale (PANSS) symptom rating scale	Basline, week 6, up to 12 weeks
Change from baseline in Paced Auditory Serial Addition Test (PASAT) score	Alternate working memory test	Basline, week 6, up to 12 weeks
Change from baseline in UCSD Performance-Based Skills Assessment (UPSA) total score	University of California, San Diego (UCSD) Performance-Based Skills Assessment Battery	Baseline, up to 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Side-Effect Scale Score	Patient self-report of side-effects of active or placebo medication	Basline, week 2, week 6, up to 12 weeks

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Collaborators: Stanley Medical Research Institute
• Investigators: Principal Investigator: Chunbo Li, M.D., Shanghai Mental Health Center

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): February 1, 2020

Study Registration Dates

• First Submitted: December 28, 2016
• First Submitted That Met QC Criteria: January 3, 2017
• First Posted (Estimate): January 5, 2017

Study Record Updates

• Last Update Posted (Actual): January 17, 2019
• Last Update Submitted That Met QC Criteria: January 15, 2019
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Inflammation; HDAC inhibitors
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Histamine Antagonists; Histamine Agents; Butyric Acid
• Other Study ID Numbers: 2016-12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Stanley foundation requests: Based on the terms of your award, Stanley Medical Research Institute (SMRI) now requires submission of the individual patient data from all SMRI funded studies. In order to make the process as efficient as possible and provide a secure location for study data, National Institute of Mental Health (NIMH) is graciously allowing SMRI access to their National Database for Clinical Trials (NDCT) to collect and house data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No