NCT02505477: NAC2

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

Completed Phase 4 Last updated 15 May 2023

What this trial tests

Phase 4 trial testing N-acetylcysteine in Schizophrenia in 51 participants. Completed in 31 January 2023.

Timeline

6 February 2017

Primary endpoint
31 January 2023

31 January 2023

Quick facts

Lead sponsor	University of California, Los Angeles
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	51
Start date	6 February 2017
Primary completion	31 January 2023
Estimated completion	31 January 2023
Sites	1 location across United States

Drugs / interventions tested

• N-acetylcysteine — full drug profile →
• Treatment as Usual

Conditions studied

• Schizophrenia — all drugs for Schizophrenia →
• Cognitive Deficits — all drugs for Cognitive Deficits →
• Schizophrenia; Negative Type — all drugs for Schizophrenia; Negative Type →

Sponsor

University of California, Los Angeles

Who can join

Adults 18 to 65, any sex, with Schizophrenia or Cognitive Deficits. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects.
   Ru Q, Li Y, Chen L, Wu Y, et al · · 2024 · cited 365× · PMID 39396974 · DOI 10.1038/s41392-024-01969-z
2. Glutamatergic Dysfunction and Glutamatergic Compounds for Major Psychiatric Disorders: Evidence From Clinical Neuroimaging Studies.
   Li CT, Yang KC, Lin WC. · · 2018 · cited 118× · PMID 30733690 · DOI 10.3389/fpsyt.2018.00767
3. Progress and Pitfalls in Developing Agents to Treat Neurocognitive Deficits Associated with Schizophrenia.
   Veselinović T, Neuner I. · · 2022 · cited 18× · PMID 35831706 · DOI 10.1007/s40263-022-00935-z
4. Is There a Glutathione Centered Redox Dysregulation Subtype of Schizophrenia?
   Palaniyappan L, Park MTM, Jeon P, Limongi R, et al · · 2021 · cited 18× · PMID 34829575 · DOI 10.3390/antiox10111703
5. Ferroptosis in Cancer and Inflammatory Diseases: Mechanisms and Therapeutic Implications.
   Shen G, Liu J, Wang Y, Deng Z, et al · · 2025 · cited 6× · PMID 40919133 · DOI 10.1002/mco2.70349
6. Confused Connections? Targeting White Matter to Address Treatment Resistant Schizophrenia.
   Crocker CE, Tibbo PG. · · 2018 · cited 5× · PMID 30405407 · DOI 10.3389/fphar.2018.01172
7. ACNP 59^th Annual Meeting: Poster Session II.
   · 2020 · cited 3× · PMID 33279935 · DOI 10.1038/s41386-020-00891-6