Efficacy of Pediococcus Acidilactici as add-on to Antipsychotic Drugs on Metabolic Syndrome Disturbances in First-episode Psychosis and Schizophrenia Spectrum Disorders. (GLUCOPSICO)

Efficacy of Pediococcus Acidilactici as add-on to Antipsychotic Drugs on Metabolic Syndrome Disturbances in First-episode Psychosis and Schizophrenia Spectrum Disorders. A Double-blind Placebo-controlled Trial.

The aim of the present study is to evaluate the effectiveness of the addition of the postbiotic Pediococcus acidilactici (pA1c®HI) on amelioration of metabolic disturbances in patients with (FEP) or (SSD) treated with antipsychotic drugs.

Study Overview

• Status: Completed
• Conditions: Metabolic Abnormalities; SCHIZOPHRENIA 1 (Disorder); Postbiotic Supplement
• Intervention / Treatment: Dietary supplement: Pediococcus acidilactici, pA1c®HI postbiotic supplementation taking participants; Drug: Atypical antipsychotics (AAP)

Detailed Description

This study aims to evaluate the effectiveness of an add-on postbiotic (Pediococcus acidilactici, pA1c®HI) to antipsychotic drugs on metabolic disturbances and psychopathological dimensions in patients diagnosed with first episode psychotic (FEP) or schizophrenia spectrum disorder (SSD).

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Navarre
    • Pamplona, Navarre, Spain, 31012
      • Navarrabiomed

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of PEP or TEESQ, according to DSM 5 criteria, aged between 18 and 65 years
• Having received antipsychotic treatment for at least 8 weeks before starting the study

Exclusion Criteria:

• Inability to give informed consent, lack of a representative or legal guardian capable of giving consent
• Intellectual disability
• Clinically significant medical condition (congestive heart failure, liver disease, renal failure, acute pancreatitis, cancer undergoing active treatment, HIV, or other immunodeficiency)
• Active substance use in the last 3 months (except nicotine)
• Antibiotic medication in the previous 14 days
• Celiac disease
• Pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FEP and postbiotic; Participants with FEP diagnostic taking postbiotic and atypical antipsychotics	Dietary supplement: Pediococcus acidilactici, pA1c®HI postbiotic supplementation taking participants; This study is the first study based on postbiotics instead of probiotics, pA1C®HI will be included as add on to the treatment with atypical antipsychotics in patients diagnosed with FEP or SSD. We include in our study the monitoring of glucose levels by means of sensors that will allow not only the recording of these average daily and weekly glucose levels but also the physical activity performed by the participant along the whole study. We also analyze the microbiota, responsible for metabolic functions, through metatranscriptome of intestinal microbiota from faecal samples from participants; Drug: Atypical antipsychotics (AAP); This study participants will continue with their established drug treatment as prescribed by their referring therapists. In the event of any changes to the treatment, the appropriate record will be made.
Experimental: SSD and postbiotic; Participants with SSD diagnostic taking postbiotic and atypical antipsychotics	Dietary supplement: Pediococcus acidilactici, pA1c®HI postbiotic supplementation taking participants; This study is the first study based on postbiotics instead of probiotics, pA1C®HI will be included as add on to the treatment with atypical antipsychotics in patients diagnosed with FEP or SSD. We include in our study the monitoring of glucose levels by means of sensors that will allow not only the recording of these average daily and weekly glucose levels but also the physical activity performed by the participant along the whole study. We also analyze the microbiota, responsible for metabolic functions, through metatranscriptome of intestinal microbiota from faecal samples from participants; Drug: Atypical antipsychotics (AAP); This study participants will continue with their established drug treatment as prescribed by their referring therapists. In the event of any changes to the treatment, the appropriate record will be made.
Placebo Comparator: FEP and placebo; Participants with FEP diagnostic taking placebo and atypical antipsychotics	Drug: Atypical antipsychotics (AAP); This study participants will continue with their established drug treatment as prescribed by their referring therapists. In the event of any changes to the treatment, the appropriate record will be made.
Placebo Comparator: SSD and placebo; Participants with SSD diagnostic taking placebo and atypical antipsychotics	Drug: Atypical antipsychotics (AAP); This study participants will continue with their established drug treatment as prescribed by their referring therapists. In the event of any changes to the treatment, the appropriate record will be made.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic Disturbances	1. Total cholesterol Description: Measurement of total cholesterol in the blood. Includes LDL, HDL, and other fractions. It is a general marker of cardiovascular risk. Units: mg/dL Ranges: Desirable: < 200 mg/dL High limit: 200-239 mg/dL High: ≥ 240 mg/dL	Beginning (week 0) and end of the study (week 12).
Metabolic Disturbances	2. LDL cholesterol (Low-Density Lipoprotein) Description: Known as "bad cholesterol." High levels are associated with atherosclerosis and cardiovascular disease. Units: mg/dL Ranges: Optimal: < 100 mg/dL Near optimal: 100-129 mg/dL High limit: 130-159 mg/dL High: 160-189 mg/dL Very high: ≥ 190 mg/dL	Beginning (week 0) and end of the study (week 12)
Metabolic Disturbances	3. HDL cholesterol (High-Density Lipoprotein) Description: Known as "good cholesterol." Helps remove cholesterol from the arteries. Units: mg/dL Ranges: Low (cardiovascular risk): Men: < 40 mg/dL Women: < 50 mg/dL Adequate/protective: ≥ 60 mg/dL	Beginning (week 0) and end of the study (week 12)
Metabolic Disturbances	4. Triglycerides Description: Type of fat in the blood related to energy metabolism. High values are associated with metabolic syndrome and cardiovascular risk. Units: mg/dL Ranges (fasting): Normal: < 150 mg/dL High limit: 150-199 mg/dL High: 200-499 mg/dL Very high: ≥ 500 mg/dL	Beginning (week 0) and end of the study (week 12)
Metabolic Disturbances	5. Plasma glucose Description: Blood glucose concentration, a key indicator of carbohydrate metabolism. Units: mg/dL Ranges (fasting): Normal: 70-99 mg/dL Impaired fasting glucose (prediabetes): 100-125 mg/dL Diabetes: ≥ 126 mg/dL	Beginning (week 0) and end of the study (week 12)
Metabolic Disturbances	6. Insulin Description: Hormone produced by the pancreas that regulates glucose uptake by tissues. Units: µU/mL (or mIU/L) Ranges (fasting): Approximate normal: 2-25 µU/mL Elevated values may suggest insulin resistance.	Beginning (week 0) and end of the study (week 12)
Metabolic Disturbances	7. Glycosylated hemoglobin (HbA1c) Description: Reflects the average blood glucose level over the past 2-3 months. Units: % Ranges: Normal: < 5.7% Prediabetes: 5.7-6.4% Diabetes: ≥ 6.5%	Beginning (week 0) and end of the study (week 12)
Metabolic Disturbances	8. HOMA-R (or HOMA-IR) Description: Index that estimates insulin resistance, calculated from fasting glucose and insulin. Formula: HOMA-IR = Insulin (µU/mL) × Glucose (mg/dL) / 405 Units: No units (index) Guideline ranges: Normal: < 2.0 Mild insulin resistance: 2.0-2.9 Significant insulin resistance: ≥ 3.0	Beginning (week 0) and end of the study (week 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Measures	Positive and Negative Symptoms 1. Positive and Negative Syndrome Scale (PANSS) Description: A widely used clinical scale for assessing the severity of positive and negative symptoms and general psychopathology in schizophrenia and other psychotic disorders. Structure: 30 items divided into: Positive subscale (7 items) Negative subscale (7 items) General psychopathology (16 items) Scoring: Each item is scored from 1 (absent) to 7 (extreme). Ranges: Total score: 30-210 The higher the score, the greater the symptom severity. Guideline interpretation (total): Mild: ~58-75 Moderate: ~75-95 Severe: >95	Along the study: week 0, week 6, and week 12
Clinical Measures	2. Brief Negative Symptoms Scale (BNSS) Description: Instrument designed specifically to assess negative symptoms in detail. Domains assessed (6): Anhedonia Asociality Avolition Affective flattening Alogia Lack of emotional distress Structure: 13 items Scoring: Items scored from 0 (absent) to 6 (severe). Total range: 0-78 Interpretation: Higher scores indicate greater severity of negative symptoms.	Along the study: week 0, week 6, and week 12
Clinical Measures	Cognitive symptoms 3. Screening for Cognitive Impairment in Psychiatry (SCIP) Description: Brief test for detecting cognitive impairment in psychiatric patients. Domains assessed: Verbal learning Working memory Verbal fluency Processing speed Delayed memory Duration: ~15 minutes Scoring: Approximate total scale 0-100 (depending on version). Interpretation: Lower scores indicate greater cognitive impairment. Cut-off points adjusted for age and educational level are used.	Along the study: week 0, week 6, and week 12
Clinical measures	4. MATRICS Consensus Cognitive Battery (MCCB) Description: Standardized reference battery for assessing cognition in schizophrenia. Domains assessed (7): Processing speed Attention/vigilance Working memory Verbal learning Visual learning Reasoning and problem solving Social cognition Score: T scores (mean = 50, SD = 10) Interpretation: T < 40: below-average performance T 40-60: normal range T > 60: above-average performance	Along the study: week 0, week 6, and week 12
Clinical Measures	5. Cognitive Reserve Assessment Scale in Health (CRASH) Description: Scale designed to estimate cognitive reserve, considering premorbid and sociocultural factors. Areas assessed: Educational level Occupation Cognitive and leisure activities Premorbid intellectual level Score: Composite index (no units). Interpretation: Higher scores indicate greater cognitive reserve, associated with a better functional prognosis. Affective symptoms 6. Calgary Depression Scale for Schizophrenia (CDSS) Description: Specific scale for assessing depressive symptoms in patients with schizophrenia, differentiating them from negative or extrapyramidal symptoms. Structure: 9 items Scoring: Items from 0 (absent) to 3 (severe). Total range: 0-27 Interpretation: ≥ 6 points suggests the presence of clinically significant depression.	Along the study: week 0, week 6, and week 12
Clinical Measures	Motor symptoms 7. Simpson-Angus Scale (SAS) Description: Instrument for assessing extrapyramidal symptoms, especially antipsychotic-induced parkinsonism. Structure: 10 items Scoring: Items from 0 (normal) to 4 (severe). Total score: Average of items or total sum. Interpretation: Higher scores indicate greater severity of motor symptoms.	Along the study: week 0, week 6, and week 12
Clinical Measures	Overall functioning 8. Global Assessment of Functioning Scale (GAF) Description: Global scale that assesses psychological, social, and occupational functioning. Range: 0-100 Interpretation: 91-100: superior functioning 71-90: minimal symptoms 51-70: mild symptoms 31-50: severe symptoms ≤ 30: severe impairment of functioning	Along the study: week 0, week 6, and week 12
Anthropometric Parameters	1. Weight Description: Measurement of the individual's total body mass. Units: kilograms (kg) Reference ranges: There are no universal "normal" ranges, as weight must be interpreted in relation to height, sex, and body composition. It is mainly used to calculate BMI.	Along the study: week 0, week 6, and week 12.
Anthropometric Parameters	2. Height Description: Body length measured in an upright position, from the soles of the feet to the top of the head. Units: centimeters (cm) or meters (m) Reference ranges: Variable depending on sex, age, and ethnicity; used primarily to calculate BMI.	Along the study: week 0, week 6, and week 12
Anthropometric Parameters	3. Body Mass Index (BMI) Description: Indirect indicator of body fat that relates weight to height. Formula: BMI = weight (kg)/height (m)2 Units: kg/m² Ranges (WHO): Underweight: < 18.5 kg/m² Normal weight: 18.5-24.9 kg/m² Overweight: 25.0-29.9 kg/m² Grade I obesity: 30.0-34.9 kg/m² Obesity grade II: 35.0-39.9 kg/m² Obesity grade III: ≥ 40 kg/m²	Along the study: week 0, week 6, and week 12
Anthropometric Parameters	4. Waist circumference Description: Measurement of abdominal circumference, used as an indicator of visceral fat and cardiometabolic risk. Units: centimeters (cm) Cut-off points (cardiometabolic risk): Men: ≥ 102 cm Women: ≥ 88 cm (Some European criteria use ≥94 cm in men)	Along the study: week 0, week 6, and week 12
Anthropometric Parameters	5. Heart rate Description: Number of heartbeats per minute at rest. Units: beats per minute (bpm) Ranges (resting, adults): Normal: 60-100 bpm Bradycardia: < 60 bpm Tachycardia: > 100 bpm	Along the study: week 0, week 6, and week 12
Anthropometric Parameters	6. Blood pressure Description: Force exerted by blood against arterial walls, expressed as systolic/diastolic pressure. Units: millimeters of mercury (mmHg) Ranges (clinical guidelines): Normal: < 120 / < 80 mmHg Elevated: 120-129 / < 80 mmHg Grade 1 hypertension: 130-139 / 80-89 mmHg Grade 2 hypertension: ≥ 140 / ≥ 90 mmHg	Along the study: week 0, week 6, and week 12
Anthropometric Parameters	7. Skin folds (Skinfold thickness) Description: Measurement of subcutaneous adipose tissue thickness using a skinfold caliper; allows estimation of body fat percentage. Units: millimeters (mm) Common measurement sites: Triceps Subscapular Suprailiac Abdominal Thigh Reference ranges: There are no universal values; results are interpreted: By summing skinfolds By applying predictive equations (e.g., Durnin-Womersley, Jackson-Pollock) Interpretation: Higher values indicate greater subcutaneous adiposity.	Along the study: week 0, week 6, and week 12

Collaborators and Investigators

• Sponsor: Manuel Jesús Cuesta Zurita
• Collaborators: Universidad Pública de Navarra; GENBIOMA Aplicaciones SL

Publications and helpful links

General Publications

• Kang, D., Zhang, F., Yang, Y., Liu, C., Xiao, J., Long, Y., Huang, J., Peng, X., Wang, W., Wang, X., Davis, J. M., Zhao, J., & Wu, R. (2021). Probiotic supplements reduce antipsychotic-induced metabolic disturbances in drug-naïve first-episode schizophrenia. https://doi.org/10.1101/2021.02.16.21251872
• Pillinger, T., McCutcheon, R. A., Vano, L., Mizuno, Y., Arumuham, A., Hindley, G., Beck, K., Natesan, S., Efthimiou, O., Cipriani, A., & Howes, O. D. (2020). Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis. The Lancet Psychiatry, 7(1), 64-77. https://doi.org/10.1016/S2215-0366(19)30416-X
• Tomasik, J., Lago, S. G., Vázquez-Bourgon, J., Papiol, S., Suárez-Pinilla, P., Crespo-Facorro, B., & Bahn, S. (2019). Association of Insulin Resistance With Schizophrenia Polygenic Risk Score and Response to Antipsychotic Treatment. JAMA Psychiatry, 76(8), 864. https://doi.org/10.1001/jamapsychiatry.2019.0304
• Yavorov-Dayliev, D., Milagro, F. I., Ayo, J., Oneca, M., & Aranaz, P. (2022). Pediococcus acidilactici CECT9879 (pA1c) Counteracts the Effect of a High-Glucose Exposure in C. elegans by Affecting the Insulin Signaling Pathway (IIS). International Journal of Molecular Sciences, 23(5), 2689. https://doi.org/10.3390/ijms23052689

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2024
• Primary Completion (Actual): January 23, 2026
• Study Completion (Actual): January 23, 2026

Study Registration Dates

• First Submitted: January 8, 2026
• First Submitted That Met QC Criteria: January 19, 2026
• First Posted (Actual): January 27, 2026

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Schizophrenia; Metabolic Syndrome; Atypical antipsychotics; First-episode psychosis; Postbiotic
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Metabolic Diseases; Glucose Metabolism Disorders; Insulin Resistance; Hyperinsulinism; Nutritional and Metabolic Diseases; Schizophrenia; Metabolic Syndrome
• Other Study ID Numbers: GLUCOPSICOBIOMICS_2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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