Treatment of Cognitive and Negative Symptoms in Schizophrenia With N-acetylcysteine

NCT02505477 | Completed Phase 4 FDA Drug

• 1 other identifier: FOS53929
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to attempt to treat cognitive and negative symptoms of schizophrenia, with the nutritional supplement N-acetylcysteine (NAC). Schizophrenia is a chronic mental disorder that affects approximately 65 million people worldwide, and causes significant disability and suffering. Patients with schizophrenia often hear voices and have persecutory delusions. Though these are the most recognizable features of the illness, the deficits most closely linked to disability are known as cognitive deficits and negative symptoms. Cognitive abilities refer to the ability to perform mental tasks that require focus and attention, and also include memory and verbal skills. Negative symptoms refer to a lack of interest in the world, and decreased social interactions. In our study, the investigators aim to improve these symptoms and deficits by targeting the glutamate system. Glutamate is the major excitatory neurotransmitter in the brain, and its regulation is abnormal in schizophrenia: glutamate levels are too low at some receptors, and too high at others. As well, free radicals surrounding glutamate receptors also interfere with their proper function. N-acetylcystine (NAC) is a safe and widely-available dietary supplement that may restore glutamate to its correct levels in the brain, and may also help protect the brain from antioxidant damage. In our study, patients with schizophrenia will be randomly assigned to receive either NAC or placebo for 8 weeks. Brain levels of glutamate and an important antioxidant, glutathione, will be measured before and after treatment, using a neuroimaging technique known as magnetic resonance spectroscopy. Cognitive and negative symptoms will also be assessed before, during and after treatment. The investigators hypothesize that glutamate and glutathione will be normalized in patients' brains, and that their negative and cognitive symptoms will be improved, too.

Conditions

Schizophrenia; Cognitive Deficits; Schizophrenia; Negative Type

Keywords

schiozphrenia; cognition; negative symptoms; glutamate; glutathione; N-acetylcysteine

Outcome Measures

Primary Outcomes (3)

• Improvement of negative symptoms

  Negative symptoms will be assessed with the PANSS and the CAINS

  0 weeks (baseline), 4 weeks and 8 weeks of treatment with NAC

• Glutamate levels in prefrontal cortex

  Patients will undergo a magnetic resonance spectroscopy scan to measure glutamate levels in prefrontal cortex

  0 weeks (baseline) and 8 weeks of treatment with NAC

• Glutathione levels in prefrontal cortex

  Patients will undergo a magnetic resonance spectroscopy scan to measure glutathione levels in prefrontal cortex

  0 weeks (baseline) and 8 weeks of treatment with NAC

Secondary Outcomes (1)

• Whole blood glutathione level

  0 weeks (baseline) and 8 weeks of treatment with NAC

Other Outcomes (1)

• Cognitive Performance on the MCCB

  0 weeks (baseline) and 8 weeks of treatment with NAC

Study Arms (2)

N-acetylcysteine

EXPERIMENTAL

Patients in this group will receive N-acetylcysteine (NAC) 1200mg orally twice daily (total daily dose 2400mg), for eight weeks. Each individual tablet contains 300mg NAC, therefore patients will take two tablets by mouth each morning and two tablets by mouth each evening. Manufacturer: Jarrow Industries, Inc.; Brand name: N-A-C Sustain

Drug: N-acetylcysteine; Other: Treatment as Usual

Placebo

PLACEBO COMPARATOR

Patients in this group will receive placebo tablets indistinguishable from NAC tablets, with the same protocol as NAC: two placebo tablets by mouth each morning, and two placebo tablets by mouth each evening. Manufacturer: Jarrow Industries, Inc.; Brand name: N-A-C Sustain

Other: Treatment as Usual

Interventions

N-acetylcysteine DRUG

N-acetylcysteine is a safe, widely available supplement currently FDA-approved for treatment of acetaminophen antidote and as a mucolytic. It has effects on glutamate in the brain via the NMDA receptor as well as the glutathione antioxidant system (it is a precursor to glutathione).

Also known as: NAC, acetylcysteine, cysteine, Acetadote

N-acetylcysteine

Treatment as Usual OTHER

Treatment for schizophrenia which may include medications, therapy, or other types of treatment as determined by the subject's VA or community psychiatrist or mental health treatment team

N-acetylcysteine; Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meet DSM-5 criteria for schizophrenia or schizoaffective disorder
• Must be able to provide informed consent to participate in the research project

You may not qualify if:

• Actively participating in other experimental drug trial(s) either currently or within the past month
• Psychiatric hospitalization within the previous three months
• Medical hospitalization or other acute medical problem within the previous three months
• A greater than 50% change in dose of antipsychotic medication within the previous three months
• They have met DSM-5 criteria for substance use disorder within the previous three months
• History of neurological illness including stroke, epilepsy, or loss of consciousness for 60 minutes or more

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

UCLA Semel Institute for Neuroscience and Human Behavior

Los Angeles, California, 90024, United States

Location

MeSH Terms

Conditions

Schizophrenia; Cognition Disorders

Interventions

Acetylcysteine; Cysteine; Therapeutics

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Neurocognitive Disorders

Intervention Hierarchy (Ancestors)

Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Sulfhydryl Compounds; Amino Acids, Neutral

Study Officials

• Yvonne Yang, MD, PhD

  Assistant Clinical Professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2015
• First Posted: July 22, 2015
• Study Start: February 6, 2017
• Primary Completion: January 31, 2023
• Study Completion: January 31, 2023
• Last Updated: May 15, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)