Exploring the Impact of Genetic Variations on The Clinical Efficacy of Nalbuphine in Postoperative Pain Management

NCT06996561 | Recruiting Phase 2 DMC

• 1 other identifier: Nal-Gene123
• Study Type: interventional
• Target: 263
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to identify the genes as well as their association with Nalbuphine. This will help the investigator to identify opioid vulnerability in Pakistani population in the postoperative patients and will contribute to overcoming the opioid crisis, resulting in better and safer outcomes. Research question is: Is there any association between the underlying genetic variations and the analgesic efficacy of Nalbuphine in postoperative patients? The Research Objectives are

1. 1.To identify the underlying genes in postoperative patients having pain.
2. 2.To find an association between identified genes and nalbuphine clinical efficacy.

Conditions

Cholecystectomy; Hernia, Abdominal; Appendectomy; Open Colorectal Surgery; Laparatomy; Postoperative Pain; Hysterectomy; Cystectomy

Keywords

genetic variations; nalbuphine; opioids; polymorphism

Outcome Measures

Primary Outcomes (1)

• pain score

  Zero is equivalent to no pain and 10 indicates the worst possible pain

  24 hours postoperatively

Secondary Outcomes (3)

• sedation score

  24 hours

• nausea vomiting score

  24 hours postoperatively

• rescue analgesia

  24 hours postoperatively

Study Arms (1)

nalbuphine

EXPERIMENTAL

Given as intravenously, 0.1-0.2 mg / kg at induction and intermittently

Drug: Nalbuphine Injection; Genetic: Next Generation Sequencing; Genetic: whole exome sequencing

Interventions

Nalbuphine Injection DRUG

Anaesthesia induction will be done with propofol (2 mg/kg) nalbuphine (0.1mg/kg) and atracurium (0.6mg/kg) intravenously. Maintenance of anaesthesia will be achieved with oxygen (O2), nitrous oxide (N2O) in 1:2 ratio and isoflurane (0.8-1%). Intermittent top up of the study drug 1-2 ml boluses will be administered if either the patient's HR or BP increased to 20 % above baseline and when other causes of tachycardia and hypertension are excluded. Timing of analgesia will be recorded. Pain will be assessed for 24 hours postoperatively using verbal rating scale (VRS) with 0 = no pain and 10 = worst pain. Sedation will be assessed as 0=no sedation, 1= mild sedation, (eye-opening on verbal commands), 2= moderate sedation (eye-opening on painful stimulus), 3= deep sedation (not waking up on pain). All patients will be prescribed paracetamol one gram IV six hourly and nalbuphine 1-2 mg IV infusion in the first 24 hours post operatively.

nalbuphine

Next Generation Sequencing GENETIC

5ml of blood samples by venipuncture will be obtained from the first 70 patients half an hour before extubation at the time of muscle closure. These blood samples will be processed for DNA analysis. Only the 15 samples where pain persisted despite nalbuphine administration, with a pain score remaining above 4, continuous use of rescue analgesia, or any documented opioid side effects (such as nausea, vomiting, or sedation), or the need for additional analgesia within 24 hours, will be sent for NGS analysis. These samples will undergo whole exome sequencing via NGS, based on patient parameters and pain scores, after being categorized as responders or non-responders to nalbuphine

Also known as: NGS, whole exome sequencing, sanger's technique

nalbuphine

whole exome sequencing GENETIC

Only the 15 samples will be sent for NGS based on patient parameters and pain scores after being categorized as responders or non-responders to nalbuphine

Also known as: NGS, next generation sequencing

nalbuphine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All adult men or women
• Age 18 to 70 years
• ASA criteria 1,2 and 3
• Abdomino-pelvic surgeries (open hernia repair, appendicectomy, open cholecystectomy, laparotomy, hysterectomy, cystectomy) lasting 2-4 hours

You may not qualify if:

• Surgical procedure duration lasting more than 4 hours
• Patients taking anti fungal fluconazole, anticoagulant (Warfarin or Clopidogrel) SNRI (Amitryptalline), Rifampicin or Buprenorphine,
• History of hypersensitivity or allergy to opioids,
• Pregnant or breastfeeding mothers,
• History of narcotic dependency, addiction, and withdrawal
• Patients experiencing any adverse side effects or complications during surgical procedure requiring intensive care admission
• Refusing to participate in the study
• Surgical procedures utilizing other modes of intraoperative analgesia e.g epidural analgesia or nerve blocks

Sponsors & Collaborators

• Dr. Asma Abdus Salam: lead

Study Sites (1)

Ziauddin University

Karachi, Sindh, 755000, Pakistan

RECRUITING

Related Publications (1)

• Agarwal D, Udoji MA, Trescot A. Genetic Testing for Opioid Pain Management: A Primer. Pain Ther. 2017 Jun;6(1):93-105. doi: 10.1007/s40122-017-0069-2. Epub 2017 Apr 13.

  PMID: 28409480 RESULT

MeSH Terms

Conditions

Hernia, Abdominal; Pain, Postoperative

Interventions

Nalbuphine; High-Throughput Nucleotide Sequencing; Exome Sequencing

Condition Hierarchy (Ancestors)

Hernia; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Postoperative Complications; Pathologic Processes; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Sequence Analysis; Genetic Techniques; Investigative Techniques; Whole Genome Sequencing; Sequence Analysis, DNA

Study Officials

• Talat Mirza, FCPS PhD

  Ziauddin University

  STUDY DIRECTOR

Central Study Contacts

Asma Abdus Salam, FCPS, MCPS, MBBS

CONTACT

+923002122264; asma.salam.azhar@gmail.com

Zulfiqar Omrani, Director ORIC

CONTACT

+9235862937; director.oric@zu.edu.pk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: May 21, 2025
• First Posted: May 30, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Beginning 3 months and ending 3 years after the publication of results
• Access Criteria: A data sharing agreement must be signed. Consent and permission should be taken from the PI and officials of Ziauddin for further publication

Locations

PA (1)