Prognostic Value of SII and SIRI in Obesity-Related Metabolic Complications (SIMO-PRO)

April 30, 2026 updated by: Gordana Kenđel Jovanović, University of Rijeka

Clinical Significance and Prognostic Value of Systemic Immune Inflammation Index and Systemic Inflammation Response Index in Obesity and Associated Metabolic Complications

This observational study aims to evaluate the diagnostic and prognostic value of the systemic immune-inflammatory index (SII) and the systemic inflammation response index (SIRI) in individuals with overweight or obesity. The study will assess their association with obesity status, metabolic complications, lifestyle patterns, dietary indices, and established inflammatory biomarkers. Participants will undergo anthropometric assessment, laboratory testing, dietary evaluation, and follow-up for response to different obesity treatment modalities over 3 years. The study intends to determine whether SII and SIRI can serve as clinically useful predictors of metabolic risk and treatment outcomes of obesity.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Obesity is a complex chronic disease associated with systemic low-grade inflammation, metabolic dysfunction, and increased risk of comorbidities such as type 2 diabetes, dyslipidemia, nonalcoholic fatty liver disease, and cardiovascular disease. Adipose tissue acts as an active endocrine organ, influencing immune regulation and inflammatory signalling. Although numerous inflammatory biomarkers have been evaluated in obesity, the diagnostic performance of novel composite systemic immune-inflammatory indices, particularly the systemic immune-inflammation index (SII) and the systemic inflammation response index (SIRI), remains inadequately characterised. SII and SIRI, derived from peripheral blood counts, have shown prognostic potential in various clinical settings but have not been systematically evaluated in predicting metabolic complications or treatment response in obesity. This study seeks to expand their application in patients with overweight and obesity by 1) evaluating the cross-sectional associations between SII/SIRI and obesity severity, inflammatory biomarkers, metabolic disorders, and dietary patterns; and 2) determining the prognostic value of SII/SIRI for predicting metabolic complications and clinical response to behavopural and lifestyle modification, pharmacotherapy, and bariatric surgery over a 1-year follow-up.

Participants will complete anthropometric measurements, comprehensive biochemical profiling, inflammatory cytokine assessment, dietary evaluation, and structured follow-up at 12 and 24 weeks, with continued monitoring of treatment response and metabolic outcomes over 1 year.

STUDY PROCEDURES (Structured per visit) Visit 1 - Baseline (Week 1)

  • Informed consent
  • Anthropometrics (height, weight, waist circumference, hip circumference, BIA)
  • Venous blood sampling: complete blood count (CBC) and differential blood count (DBC), fasting glucose, HbA1c, lipid profile (cholesterol, LDL, HDL, triglycerides), thyroid panel (TSH, FT4, FT3), liver panel, renal panel, CRP, cortisol, bilirubin, iron status parameters, vitamins/minerals (Ca, P, Mg, vitamin D)
  • Biobanking: 3 frozen aliquots for hs-CRP, adiponectin, IL-6, TNF-α
  • Lifestyle and dietary questionnaires (socio-demographics, physical activity, smoking, sleep, stress, medication use; 24 h dietary recall + FFQ)
  • Motivational and educational counselling (diet, activity, pharmacotherapy options)

Visit 2 - Week 12

  • Anthropometrics + BIA
  • Laboratory testing (repeated, as above)
  • Assessment of dietary and lifestyle adherence
  • Motivational counselling (in person or telephone)

Visit 3 - Week 24

  • Anthropometrics + BIA
  • Full biochemical panel
  • Dietary questionnaires (24 h recall+MEDAS+Short Diet Screener)
  • Evaluation of treatment response to lifestyle intervention, pharmacotherapy, or bariatric surgery
  • Motivational counselling

LONG-TERM FOLLOW-UP (Year 1)

  • Monitoring metabolic outcomes
  • Evaluation of obesity treatment response
  • Prognostic assessment of SII/SIRI

Study Type

Observational

Enrollment (Estimated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Gordana Kenđel Jovanović, Asst.Prof.
  • Phone Number: +385912030704
  • Email: gordanakj@uniri.hr

Study Contact Backup

  • Name: Jelena Vresk Špiranec, MD, spec. endocrinology
  • Phone Number: +385995112141
  • Email: jelenavresk@gmail.com

Study Locations

  • Croatia
      • Varaždin, Croatia
        • Recruiting
        • General Hospital Varazdin
        • Contact:
          • Jelena Vresk Špiranec, MD, specialist in endocrinolog
          • Phone Number: +385995112141
          • Email: jelenavresk@gmail.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The study population consists of adults with overweight or obesity who are receiving obesity management at outpatient obesity clinics. Eligible participants are 18 years or older and have a BMI between 25.0-29.9 kg/m² (overweight) or BMI ≥ 30 kg/m² (obesity). All participants must be able to attend scheduled clinical visits and must provide written informed consent.

Description

Inclusion Criteria

  • Age ≥ 18 years
  • BMI 25.0-29.9 kg/m² (overweight) or BMI ≥ 30 kg/m² (obesity)
  • Ability to attend scheduled clinical visits
  • Willingness to provide informed consent

Exclusion Criteria

  • Pregnancy or breastfeeding
  • Use of immunosuppressive therapy
  • Active infection
  • Inflammatory disease
  • Malignancy
  • Acute illness affecting immune parameters
  • Conditions interfering with study participation (as assessed by the investigator)
  • Known hematologic disorders affecting leukocyte or platelet counts
  • Chronic inflammatory diseases requiring systemic therapy
  • Recent major surgery (within the last 3 months)
  • Any condition that could confound the relationship between SII/SIRI and obesity-driven inflammation, such as immune disorders

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Overweight and obesity cohort
Adults with overweight or obesity presenting to outpatient obesity clinics. Participants aged ≥18 years with BMI ≥25 kg/m² undergoing clinical evaluation for obesity. All participants will follow the same assessment and follow-up schedule; variation occurs only in the type of treatment chosen (lifestyle, pharmacotherapy, bariatric surgery).
Behavioral: Nutritional counselling
Participants will receive interventions that are part of routine medical care, i.e. structured personalised nutritional intervention aligned with the Croatian Guidelines for the Treatment of Adults with Obesity. It emphasises lifestyle modification, energy-reduced dietary patterns, and the adoption of healthy eating habits as the first-line approach to weight management. The intervention consists of a 30-minute individualised counselling session delivered by a licensed nutrition professional. During the session, participants are guided to adopt a Mediterranean diet, with goal-setting, portion guidance, and strategies to increase adherence. The routine medical intervention aligned with the guidelines' recommendation for a nutritionally balanced diet combined with a modest daily energy deficit (~500 kcal) to support gradual, sustainable weight loss and long-term weight maintenance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnostic and prognostic value of SII and SIRI
Time Frame: baseline, 24 weeks and at study completion, an average of 1 year
The diagnostic and prognostic value of systemic inflammation indices (SII and SIRI) will be assessed using ROC curve analysis, including sensitivity, specificity, and AUC calculations.
baseline, 24 weeks and at study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Association of SII and SIRI with Metabolic Complications
Time Frame: baseline, 24 weeks and at study completion, an average of 1 year
The association of SII and SIRI with metabolic complications (insulin resistance, dyslipidemia, NAFLD) and their ability to predict response to obesity treatment (behavioural and pharmacologic) will be evaluated.
baseline, 24 weeks and at study completion, an average of 1 year
Association of SII and SIRI with Dietary Patterns
Time Frame: baseline, 24 weeks and at study completion, an average of 1 year
The relationship between SII/SIRI and adherence to anti-inflammatory and pro-inflammatory dietary patterns will be examined using indices such as the Mediterranean Diet Index and the Dietary Inflammatory Index. The analysis will provide insight into the impact of diet quality on systemic inflammation over time.
baseline, 24 weeks and at study completion, an average of 1 year
Identification of Prognostic Markers of Metabolic Comorbidities
Time Frame: baseline, 12 weeks, 24 weeks, and at study completion, an average of 1 year
Inflammatory indices (SII, SIRI) and monitored biomarkers will be analysed to determine their ability to predict the development or progression of obesity-related metabolic complications. The aim is to identify early indicators of increased risk for adverse metabolic outcomes and help in providing timely and appropriate obesity management.
baseline, 12 weeks, 24 weeks, and at study completion, an average of 1 year
Changes in SII and SIRI During Treatment
Time Frame: baseline, 12 weeks, 24 weeks, and at study completion, an average of 1 year
Longitudinal changes in SII and SIRI will be monitored throughout the treatment period to assess the degree and sustainability of systemic inflammation reduction. Results will be associated with clinical outcomes and treatment effectiveness.
baseline, 12 weeks, 24 weeks, and at study completion, an average of 1 year
Relationship Between SII/SIRI and Inflammatory Biomarkers
Time Frame: baseline, 12 weeks, 24 weeks, and at study completion, an average of 1 year
The associations between SII and SIRI and inflammatory biomarkers will be examined to confirm their biological significance and diagnostic value. This analysis will contribute to understanding the mechanisms of systemic inflammation in the context of obesity and metabolic disorders.
baseline, 12 weeks, 24 weeks, and at study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Rijeka

Investigators

  • Principal Investigator: Gordana Kenđel Jovanović, Asst. Prof., Faculty of Medicine, University of Rijeka
  • Study Director: Sanja Klobučar, Assoc.Prof., Faculty of Medicine, University of Rijeka; Clinical Hospital Rijeka

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2026

Primary Completion (Estimated)

April 28, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

February 11, 2026

First Submitted That Met QC Criteria

February 18, 2026

First Posted (Actual)

February 24, 2026

Study Record Updates

Last Update Posted (Actual)

May 7, 2026

Last Update Submitted That Met QC Criteria

April 30, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MEDRI-47-2025

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Participants' demographics, obesity management treatments, and outcomes.

IPD Sharing Time Frame

The IPD will be available after the completion of the study, starting on 1st January of 2028, to January of 2033.

IPD Sharing Access Criteria

Access will be provided to qualified researchers engaged in independent scientific research. Anonymised or pseudonymized participant-level data will be shared to protect privacy. Data will be provided via a secure, managed-access data sharing repository.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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