The Effect of Lactoferrin on Pain Management Following Cesarean Section

This study evaluates whether lactoferrin, a naturally occurring protein with anti-inflammatory and antioxidant properties, can improve pain control after cesarean section. Effective management of postoperative pain is essential to support maternal recovery, mobility, and the ability to care for the newborn, while minimizing reliance on opioid medications and their associated side effects.

In this randomized, double-blind, placebo-controlled trial, women undergoing elective cesarean section will receive either oral lactoferrin or a matching placebo in addition to standard postoperative analgesia. Lactoferrin will be administered starting before surgery and continued for 48 hours after delivery.

The study will assess whether lactoferrin reduces postoperative pain intensity and opioid consumption, and improves recovery outcomes such as time to mobilization, patient satisfaction, and incidence of common postoperative symptoms. Safety and tolerability will also be evaluated.

Study Overview

• Status: Not yet recruiting
• Conditions: Post Operative Analgesia; Cesarean Birth
• Intervention / Treatment: Drug: Lactoferrin; Other: Placebo

Detailed Description

Cesarean section is one of the most commonly performed surgical procedures worldwide, and optimal postoperative pain control remains a clinical priority. Inadequate pain management can delay recovery, impair maternal-infant interaction, prolong hospitalization, and increase the risk of complications such as thromboembolism. Although opioids are effective for postoperative analgesia, their use is limited by dose-dependent adverse effects, prompting the need for adjunctive therapies that enhance analgesia while reducing opioid requirements.

Lactoferrin is a naturally occurring iron-binding glycoprotein present in breast milk and other body secretions, with well-documented anti-inflammatory, antioxidant, and immunomodulatory properties. Experimental and clinical evidence suggests that lactoferrin modulates key inflammatory mediators involved in pain signaling, including pro-inflammatory cytokines, and may exert antinociceptive effects through both peripheral and central mechanisms. These properties support its potential role as an adjunct in postoperative pain management; however, its efficacy in this setting has not been evaluated in a randomized clinical trial.

This study is designed as a prospective, randomized, double-blind, placebo-controlled clinical trial to evaluate the effect of lactoferrin on postoperative pain following elective cesarean section. Eligible participants will be randomized in a 1:1 ratio to receive either oral lactoferrin (250 mg twice daily) or a matching placebo. The first dose will be administered one hour prior to surgery, followed by continued dosing every 12 hours for 48 hours postoperatively. All participants will receive standardized spinal anesthesia and routine perioperative and postoperative analgesic care.

The primary objective is to assess the effect of lactoferrin on postoperative pain intensity, measured using a visual analog scale at predefined time points within the first 24 hours after surgery. Secondary objectives include evaluation of opioid consumption, time to first request for rescue analgesia, incidence of postoperative nausea and vomiting, other postoperative symptoms, time to mobilization, functional recovery, patient satisfaction, and hospital length of stay.

Safety will be assessed through monitoring of adverse events, including gastrointestinal symptoms, allergic reactions, and other treatment-related effects. All adverse events will be documented and evaluated for severity and causality.

The sample size has been calculated to provide adequate statistical power to detect clinically meaningful differences in primary and secondary outcomes between groups. Statistical analyses will be conducted using an intention-to-treat approach with appropriate methods for continuous and categorical variables.

This trial aims to provide clinical evidence on the potential role of lactoferrin as a safe and effective adjunct to standard analgesic regimens for improving postoperative pain control and recovery following cesarean section.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11856
    • Mansoura Hospital
    • Contact: Khaled Samir Associate Professor of gynecology, MD; Phone Number: +201097452797; Email: khalid_samir@mans.edu.eg

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Referred to elective (non-emergency) cesarean section
• Undergoing spinal anesthesia) with American Society of Anesthesiologists (ASA) classification I and II
• Term gestational age

Exclusion Criteria:

• History of seizures
• Pre-eclampsia or eclampsia
• Hypertension
• Use of narcotic painkillers for 24 h before the intervention
• Medications inducing neuropathy including Amiodarone, Metronidazole, Phenytoin & Colchicine.
• Prolongation of cesarean section (more than 1.5 h)
• Increase in the size of the incision
• Occurrence of any unusual complication during surgery,
• Failure of spinal anesthesia and its conversion to general anesthesia
• Contraindications to spinal anesthesia
• Use of interacting medication: fluoroquinolones, loratadine, fexofenadine, alvimopan, armodafinil

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lactoferrin; Lactoferrin 250 mg orally twice daily (BID). The first dose will be given 1 hour preoperatively, followed by repeat doses every 12 hours for 48 hours postoperatively	Drug: Lactoferrin; Lactoferrin 250 mg orally twice daily (BID). The first dose will be given 1 hour preoperatively, followed by repeat doses every 12 hours for 48 hours postoperatively
Placebo Comparator: Placebo; will receive matching placebo capsules administered on the same schedule as the lactoferrin group (first dose 1 hour preoperatively, then every 12 hours for 48 hours).	Other: Placebo; matching placebo capsules administered on the same schedule as the lactoferrin group (first dose 1 hour preoperatively, then every 12 hours for 48 hours).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity ( 2 hours)	Pain intensity using 10 cm Visual analogue scale (VAS)	2 hours
Pain intensity (6 hours)	pain intensity using 10 cm visual analogue scale (VAS)	6 hours
Pain intensity (12 hours)	pain intensity using 10 cm visual analogue scale (VAS)	12 hours
Pain intensity (24 hours)	pain intensity using 10 cm visual analogue scale (VAS)	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
nausea and vomiting ( 2 hours)	severity of nausea/ vomiting (n/v) using a numerical scale from 0 to 2 (0=no nausea, 1= mild n/v, and 2= severe n/v)	2 hours
nausea and vomiting (6 hours)	severity of nausea/ vomiting (n/v) using a numerical scale from 0 to 2 (0=no nausea, 1= mild n/v, and 2= severe n/v)	6 hours
nausea and vomiting (12 hours)	severity of nausea/ vomiting (n/v) using a numerical scale from 0 to 2 (0=no nausea, 1= mild n/v, and 2= severe n/v)	12 hours
nausea and vomiting (24 hours)	severity of nausea/ vomiting (n/v) using a numerical scale from 0 to 2 (0=no nausea, 1= mild n/v, and 2= severe n/v)	24 hours
Rescue analgesia	The patient's first request for post operative analgesia	24 hours
opioid intake	the patient's opioid intake in the 24 hours after surgery	24 hours

Collaborators and Investigators

• Sponsor: Ain Shams University

Publications and helpful links

General Publications

• Mohamed Elmokadem E, Khaled Abou El Fadl D, Bassiouny AM, Mahmoud MMAE, Samy M, El Said NO. The Adjunctive Effect of Quercetin on Postoperative Pain Management Following Cesarean Section: A Randomized Controlled Study. Drug Des Devel Ther. 2025 Jul 14;19:6009-6024. doi: 10.2147/DDDT.S526188. eCollection 2025.

Study record dates

Study Major Dates

• Study Start (Estimated): March 26, 2026
• Primary Completion (Estimated): August 26, 2026
• Study Completion (Estimated): September 26, 2026

Study Registration Dates

• First Submitted: March 25, 2026
• First Submitted That Met QC Criteria: March 25, 2026
• First Posted (Actual): March 30, 2026

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: post operative pain; analgesia; post operative analgesia; lactoferrin; pain management; obstetric surgery
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Neurobehavioral Manifestations; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Agnosia; Amino Acids, Peptides, and Proteins; Proteins; Carbohydrates; Hydrolases; Enzymes; Enzymes and Coenzymes; Globulins; Glycoproteins; Glycoconjugates; Endopeptidases; Peptide Hydrolases; Serine Endopeptidases; Serine Proteases; Dietary Proteins; Milk Proteins; Animal Proteins, Dietary; Carrier Proteins; Transferrins; Iron-Binding Proteins; Lactoglobulins; Whey Proteins; Metalloproteins; Lactoferrin
• Other Study ID Numbers: REC-FPFUE_NO 6/2026

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