PQQ for Cognitive and Negative Symptoms

The Efficacy and Safety of Pyrroloquinoline Quinone add-on Treatment for Negative and Cognitive Symptoms in Chronic Schizophrenia

Schizophrenia is a complex mental disorder characterized by a range of symptoms, including negative symptoms and cognitive impairments. Recent research has indicated the potential benefits of targeting mitochondrial dysfunction, oxidative stress, and inflammatory responses in alleviating symptoms of schizophrenia. However, the results remain inconsistent across various studies. This study aims to evaluate the efficacy of Pyrroloquinoline quinone (PQQ) in reducing negative symptoms and improving cognitive function in patients with chronic schizophrenia. The investigation will focus on changes in severity scores from baseline to endpoint, as well as during an eight-week follow-up period. A double-blind, randomized controlled trial will be conducted involving participants diagnosed with chronic schizophrenia. Participants will be randomly assigned to receive either PQQ or a matched placebo. Data will be collected through questionnaires and neuroimaging techniques, including resting-state scans and multimodal tasks to assess functional connectivity and activation in target brain regions. Statistical analyses will include descriptive statistics, voxel-by-voxel multiple regression, and linear mixed models to account for repeated measurements. Additionally, potential moderating effects of demographic factors such as age and gender will be examined using ANCOVAs. The study will also monitor adverse events and ensure participant safety through a rigorous reporting and unblinding procedure. It is hope to provide insights into the therapeutic potential of PQQ in managing schizophrenia symptoms, contributing to the development of more effective treatment strategies for this challenging condition.

Study Overview

• Status: Not yet recruiting
• Conditions: Schizophrenia; Negative Symptoms; Cognitive Symptoms
• Intervention / Treatment: Dietary supplement: Pyrroloquinoline quinone (PQQ); Dietary supplement: placebo (dietary fiber)

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Daxiang Medical Ethics Committee of Tianjin Anding Hospital; Phone Number: 0086-22-88188631; Email: tjadllwyh@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

Eligible male and female patients aged 18 to 50 years, diagnosed with schizophrenia according to the criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5), will be included in the study. Participants are required to meet the following criteria: a Positive and Negative Syndrome Scale (PANSS) total scores of ≥ 60 (indicating an active phase of the illness), a PANSS negative subscale scores of ≥ 20, and a duration of illness of at least 2 years (indicating chronic schizophrenia). Additionally, participants must have been on a stable dose of antipsychotic medication for a minimum of 6 weeks prior to enrollment, and the use of antioxidants or anti-inflammatory medications is prohibited within 2 weeks preceding enrollment.

Exclusion criteria:

Patients with comorbid psychiatric disorders as defined by the DSM-5, such as substance abuse or dependence (excluding nicotine), or intellectual disability (IQ < 70); those with significant depressive symptoms, defined as a score ≥14 on the 17-item Hamilton Depression Rating Scale (HAMD-17) or ≥ 4 on the depression item of PANSS; individuals with severe medical or neurological conditions, or those unable to communicate effectively; patients with a known allergy to PQQ disodium salt, or who are pregnant, breastfeeding, or have severe hepatic or renal impairment; women of childbearing potential who are not using reliable contraception; patients who have received modified electroconvulsive therapy (MECT) or other physical treatments within six months prior to enrollment; and those currently receiving treatments that cannot be discontinued, including antidepressants, mood stabilizers, antihistamines, or combination therapy with two or more antipsychotics (except for low-dose aripiprazole, ≤ 5 mg/day, used solely for prolactin reduction).

Additional exclusion criteria for participants undergoing fMRI scanning:

Participants are required to complete a comprehensive safety questionnaire addressing potential risks associated with exposure to a 3-Tesla magnetic field and the MRI environment. MRI-specific exclusion criteria include: the presence of MRI-incompatible implants (e.g., cochlear implants, insulin pumps, pacemakers, or other metallic implants); a history of possible intraocular metallic foreign bodies due to manual labor without appropriate eye protection; tattoos containing red pigments; claustrophobia; or unwillingness to be informed of any incidental structural brain abnormalities detected during the scan.

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
Placebo Comparator: Control group	Dietary supplement: placebo (dietary fiber); Patients with chronic schizophrenia in control group will a capsule of placebo orally every day for a total of 12 weeks.
Experimental: PQQ group	Dietary supplement: Pyrroloquinoline quinone (PQQ); Patients with chronic schizophrenia in experimental group will take 20 mg of PQQ orally every day for a total of 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cognitive symptoms	the changes in scores of MCCB between the baseline and the first post-treatment measurement.	From enrollment to the end of 12 weeks
negative symptoms	the changes in scores of PANSS negative subscale between the baseline and the first post-treatment measurement.	From enrollment to the end of 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
congtive/negative symptoms	the scores of MCCB/PANSS negative subscale at the eight-week follow-up after withdrawal of PQQ treatment	From enrollment to the end of 20 weeks
Malondialdehyde, Mitochondrial DNA, and Glutathione Peroxidase	The levels of biomarkers representing oxidative stress and inflammatory activity are assessed in venous blood.	From enrollment to the end of 12 weeks and 20 weeks
Connectivity strength of target neural circuits	The functional state of target brain regions and the connectivity strength of key neural circuits, including the prefrontal-parietal cognitive control network, the hippocampal-prefrontal memory circuit, and the thalamo-cortical information gating system.	From enrollment to the end of 12 weeks and 20 weeks

Collaborators and Investigators

• Sponsor: Tianjin Anding Hospital

Publications and helpful links

General Publications

• Tamakoshi M, Suzuki T, Nishihara E, Nakamura S, Ikemoto K. Pyrroloquinoline quinone disodium salt improves brain function in both younger and older adults. Food Funct. 2023 Mar 6;14(5):2496-2501. doi: 10.1039/d2fo01515c.
• Nunome K, Miyazaki S, Nakano M, Iguchi-Ariga S, Ariga H. Pyrroloquinoline quinone prevents oxidative stress-induced neuronal death probably through changes in oxidative status of DJ-1. Biol Pharm Bull. 2008 Jul;31(7):1321-6. doi: 10.1248/bpb.31.1321.
• Zhang P, Xu Y, Li L, Jiang Q, Wang M, Jin L. In vitro protective effects of pyrroloquinoline quinone on methylmercury-induced neurotoxicity. Environ Toxicol Pharmacol. 2009 Jan;27(1):103-10. doi: 10.1016/j.etap.2008.08.010. Epub 2008 Sep 7.
• Xiao L, Wang M, Li J, Wang H, Pu N, Bo X, Chen F, Zhou Y, Cheng Q. Pyrroloquinoline Quinone Preconditioning Alleviates Ischemic Cerebral Injury Through Antioxidant and Anti-Inflammatory Mechanisms. J Neuroimmune Pharmacol. 2025 Jul 23;20(1):75. doi: 10.1007/s11481-025-10234-1.

Study record dates

Study Major Dates

• Study Start (Estimated): February 15, 2026
• Primary Completion (Estimated): February 15, 2028
• Study Completion (Estimated): April 15, 2028

Study Registration Dates

• First Submitted: January 31, 2026
• First Submitted That Met QC Criteria: January 31, 2026
• First Posted (Actual): February 6, 2026

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 6, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: schizophrenia; cognitive symptom; Pyrroloquinoline Quinone; negative symptom; MCCB
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Schizophrenia; Neurobehavioral Manifestations; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Dietary Carbohydrates; Carbohydrates; Enzymes and Coenzymes; Coenzymes; Quinolones; Quinolines; Dietary Fiber; PQQ Cofactor
• Other Study ID Numbers: TJPQQ2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: required the permission from the PI
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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