The Effect of Curcumin on Inflammatory Markers in Hemodialysis Patients

1. Study Title:

"Effect of Curcumin on the Reduction of Cellular Inflammation Markers in Hemodialysis Patients" 2. Study Design:

Type: Randomized, double-blind, placebo-controlled clinical trial. * Setting: Antiguo Hospital Civil de Guadalajara "Fray Antonio Alcalde," Mexico. * Participants: 34 CKD patients on hemodialysis or peritoneal dialysis, aged 18+. * Intervention: Patients will receive either curcumin (500 mg capsules, 3 times daily) or placebo for 12 weeks with pre- and post-intervention assessments. 3. Objectives:

Primary Objective: To evaluate the effect of curcumin supplementation on inflammatory markers (TNF-α, IL-1β, IL-6, and CRP) in hemodialysis patients.

Secondary Objectives: * To assess changes in renal metabolites (creatinine, urea, proteinuria). * To monitor nutritional status (weight, BMI, muscle mass, dynamometry). * To identify potential side effects or adverse reactions associated with curcumin supplementation. 4. Study Population:

Inclusion Criteria: * Patients aged 18 years or older. * Clinically stable and receiving hemodialysis for at least 3 months prior to enrollment. * Willing to provide informed consent.

Exclusion Criteria: * Active malignancy, severe infections, or systemic inflammatory diseases. * Liver disease (ALT/AST \> 3x upper limit of normal). * Use of immunosuppressants, corticosteroids, or experimental drugs within the last month. * Pregnancy, smoking, or allergies to curcumin. * Recent antibiotic use (within the last 3 months). 5. Sample Size:

Calculation: Based on a previous study (Afshar et al., 2020), a sample size of 17 patients per group (34 total) was determined to detect a significant difference in CRP levels with 80% power and a 20% dropout rate. 6. Randomization and Blinding:

Randomization: Patients will be randomly assigned to either the curcumin or placebo group using sealed, opaque envelopes.

Blinding: Both participants and investigators will be blinded to the treatment allocation. The placebo capsules will be identical in appearance to the curcumin capsules. 7. Intervention:

* Curcumin Group: Patients will receive 500 mg curcumin capsules (Longvida® with 20% curcuminoids) two times daily (total of 1 g/day) for 12 weeks. * Placebo Group: Patients will receive identical-looking placebo capsules (containing starch) on the same schedule.

Adherence Monitoring: Patients will be provided with a calendar to track capsule consumption. Adherence will be considered good if ≥80% of capsules are consumed. 8. Data Collection:

* Baseline and Post-Intervention Assessments: * Inflammatory Markers: TNF-α, IL-1β, IL-6, and CRP levels will be measured using ELISA. * Renal Function: Serum creatinine, urea, proteinuria, and other renal markers will be assessed. * Nutritional Status: Weight, height, BMI, body composition (fat and muscle mass), and handgrip strength (dynamometry) will be measured. * Dietary Habits: A 3-day dietary diary will be used to assess protein, fat, fiber, sodium, potassium, and phosphorus intake. * Adverse Events: Any side effects or adverse reactions will be recorded during weekly follow-ups. 9. Laboratory Procedures:

* Blood Samples: Collected before and after the intervention. Samples will be centrifuged and stored at -80°C for biomarker analysis. * ELISA Analysis: Inflammatory markers (TNF-α, IL-1β, IL-6, CRP) will be quantified using commercially available ELISA kits. * Renal Function Tests: Performed in the hospital's clinical laboratory using standard methods. 10. Statistical Analysis:

-Descriptive Statistics: Mean, median, standard deviation, and frequencies will -be calculated for continuous and categorical variables.

Inferential Statistics: * Normality will be assessed using Kolmogorov-Smirnov or Shapiro-Wilk tests. * Parametric tests (t-tests) or non-parametric tests (Mann-Whitney U) will be used to compare groups. * Chi-square or Fisher's exact tests will be used for categorical variables. * Changes in inflammatory markers and renal function will be analyzed using paired tests (pre- vs. post-intervention).

Software: SPSS (version 17.0) and GraphPad Prism (version 10.3.0) will be used for data analysis. 11. Ethical Considerations:

* Approval: The study protocol has been approved by the Ethics Committee of the Antiguo Hospital Civil de Guadalajara. * Informed Consent: All participants will provide written informed consent before enrollment. * Confidentiality: Patient data will be anonymized and stored securely. Only the research team will have access to identifiable information. * Participant Rights: Participation is voluntary, and patients may withdraw at any time without affecting their medical care. 12. Timeline:

* May-Oct 2024: Literature review and protocol development. * Jan-Mar 2025: Ethical approval and patient recruitment. * Mar-Dec 2026: Intervention period and data collection. * Dec 2026: Data analysis and manuscript preparation. * 2027: Publication and dissemination of results.

• Urea [Time frame: before supplementation]
• Urea [Time frame: after 3 months of supplementation]
• leukocyte count [Time frame: before supplementation]
• leukocyte count [Time frame: after 3 months of supplementation]
• neutrophil/lymphocyte ratio (NLR) [Time frame: before supplementation]
• neutrophil/lymphocyte ratio (NLR) [Time frame: after 3 months of supplementation]
• lymphocyte/platelet ratio (LPR) [Time frame: before supplementation]
• lymphocyte/platelet ratio (LPR) [Time frame: after 3 months of supplementation]
• erythrocyte sedimentation rate (ESR) [Time frame: before supplementation]
• erythrocyte sedimentation rate (ESR) [Time frame: after 3 months of supplementation]
• serum albumin [Time frame: before supplementation]
• serum albumin [Time frame: after 3 months of supplementation]