CholecystectomyPhase 2/3NalNCT06996561
Exploring the Impact of Genetic Variations on The Clinical Efficacy of Nalbuphine in Postoperative Pain Management
A Phase 2/3 study testing Nalbuphine Injection, Next Generation Sequencing and whole exome sequencing in people with Cholecystectomy and Hernia, Abdominal, run by Dr. Asma Abdus Salam at 1 site in Pakistan.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Cholecystectomy, Hernia, Abdominal, Appendectomy
- What is being tested?
- Nalbuphine Injection, Next Generation Sequencing and whole exome sequencing
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 263 participants
- Where
- 1 sitePakistan
- Study dates
- 1 Sep 2025to 30 Jun 2027
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Pakistan1 site, 1 recruiting
- Recruiting
Ziauddin University
Karachi, Sindh, 755000
Asma Abdus Salam, FCPS MCPS MBBS, 03002122264, asma.salam.azhar@gmail.com
Ambrina Associate Professor, PhD, ambrina.khatoon@zu.edu.pk
About this study
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:
Read more
Is there any association between the underlying genetic variations and the analgesic efficacy of Nalbuphine in postoperative patients? The Research Objectives are
- To identify the underlying genes in postoperative patients having pain.
- To find an association between identified genes and nalbuphine clinical efficacy.
Procedure: After the written informed consent adult men and women will be enrolled in the study. On the day of surgery in the preoperative area, a 5 ml blood sample will be drawn before surgery and will be sent to laboratory for analysis. After routine hemodynamic monitoring in the operative room, general anesthesia will be given including nalbuphine. Standard routine anesthesia monitoring will be done and maintained while monitoring heart rate, ECG, NIBP oxygen saturation, ETCO2 and temperature. Incremental analgesia will be provided whenever needed. After extubation and shifting to recovery room the 2nd sample of blood will be taken and will be sent for analysis. Pain score, nausea vomiting, sedation, requirement of analgesia will be assessed till 24 hours postoperatively.
Read the detailed description
The available data suggests that nalbuphine, tramadol, and morphine exhibit comparable efficacy in treating moderate to severe postoperative pain. However, significant individual variations exist in the analgesic response, which can be attributed to genetic differences. These are the variations that are influenced by a combination of demographic, clinical, and environmental factors with a significant contribution from genetic factors that regulate receptor function and signal transduction. Due to the limited availability of morphine, nalbuphine is an extensively used alternative for managing intraoperative and postoperative pain in many LMICs, particularly in Pakistan. While nalbuphine is clinically effective, there is a gap in understanding the molecular factors that contribute to its efficacy in this genetically distinct population. This highlights the need to investigate the genetic variability and to establish the analgesic efficacy of nalbuphine within Pakistani population. There is no molecular data from the region where the investigator belongs, which highlights the importance of genetic testing to tailor opioid therapy to individual needs, optimizing pain management while minimizing risks such as overdose or inadequate pain relief. By implementing genetics into clinical practice, the investigator can offer more personalized, effective, and safer opioid use, addressing the challenges associated with opioid therapy in diverse patient populations.
- Conditions
- Cholecystectomy, Hernia, Abdominal, Appendectomy, Open Colorectal Surgery, Laparatomy, Postoperative Pain
- Being tested
- Nalbuphine Injection, Next Generation Sequencing, whole exome sequencing
- Keywords
- genetic variations, nalbuphine, opioids, polymorphism
- Medical subject headings
- Hernia, Abdominal, Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nalbuphine InjectionDrug
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.
Next Generation SequencingGenetic
Also called NGS, whole exome sequencing, sanger's technique
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
whole exome sequencingGenetic
Also called NGS, next generation sequencing
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
| Study group | Role | What they receive |
|---|---|---|
| nalbuphine | Experimental | Given as intravenously, 0.1-0.2 mg / kg at induction and intermittently Receives: Drug: Nalbuphine Injection; Genetic: Next Generation Sequencing; Genetic: whole exome sequencing |
What is being measured
The primary outcome is the main question the study is designed to answer.
pain score
Zero is equivalent to no pain and 10 indicates the worst possible pain
Measured: 24 hours postoperatively
Secondary outcomes (3)
sedation score
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).
Measured: 24 hours
nausea vomiting score
- as no nausea and vomiting and 3 as continous vomiting despite giving antiemetic
Measured: 24 hours postoperatively
rescue analgesia
How much nalbuphine ( opioid) in mg was needed in 24 hours. will signify those not responding to conventional analgesia
Measured: 24 hours postoperatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2025
- Study start1 Sep 2025
- Primary completion1 Jan 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CholecystectomyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 263 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dr. Asma Abdus Salam
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dr. Asma Abdus Salam, Ziauddin University
- Investigators
- Talat Mirza, FCPS PhD, Study director, Ziauddin University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06996561
- Sponsor's protocol ID
- Nal-Gene123
- Acronym
- Nal
- Status last verified
- Apr 2026
- First submitted
- 21 May 2025
- Last updated
- 15 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: only IPD used in the results publication
Publications
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.
PubMed 28409480
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploring the Impact of Genetic Variations on The Clinical Efficacy of Nalbuphine in Postoperative Pain Management
- ClinicalTrials.gov ID
- NCT06996561
- Acronym / sponsor ID
- Nal / Nal-Gene123
- Conditions
- Cholecystectomy, Hernia, Abdominal, Appendectomy, Open Colorectal Surgery, Laparatomy, Postoperative Pain
- Keywords
- genetic variations, nalbuphine, opioids, polymorphism
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 263 participants (estimated)
- Lead sponsor
- Dr. Asma Abdus SalamUniversity, hospital or other
- Study start
- 1 Sep 2025 (actual)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 30 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- To identify the underlying genes in postoperative patients having pain.
- To find an association between identified genes and nalbuphine clinical efficacy.
Procedure: After the written informed consent adult men and women will be enrolled in the study. On the day of surgery in the preoperative area, a 5 ml blood sample will be drawn before surgery and will be sent to laboratory for analysis. After routine hemodynamic monitoring in the operative room, general anesthesia will be given including nalbuphine. Standard routine anesthesia monitoring will be done and maintained while monitoring heart rate, ECG, NIBP oxygen saturation, ETCO2 and temperature. Incremental analgesia will be provided whenever needed. After extubation and shifting to recovery room the 2nd sample of blood will be taken and will be sent for analysis. Pain score, nausea vomiting, sedation, requirement of analgesia will be assessed till 24 hours postoperatively.
Detailed description
The available data suggests that nalbuphine, tramadol, and morphine exhibit comparable efficacy in treating moderate to severe postoperative pain. However, significant individual variations exist in the analgesic response, which can be attributed to genetic differences. These are the variations that are influenced by a combination of demographic, clinical, and environmental factors with a significant contribution from genetic factors that regulate receptor function and signal transduction. Due to the limited availability of morphine, nalbuphine is an extensively used alternative for managing intraoperative and postoperative pain in many LMICs, particularly in Pakistan. While nalbuphine is clinically effective, there is a gap in understanding the molecular factors that contribute to its efficacy in this genetically distinct population. This highlights the need to investigate the genetic variability and to establish the analgesic efficacy of nalbuphine within Pakistani population. There is no molecular data from the region where the investigator belongs, which highlights the importance of genetic testing to tailor opioid therapy to individual needs, optimizing pain management while minimizing risks such as overdose or inadequate pain relief. By implementing genetics into clinical practice, the investigator can offer more personalized, effective, and safer opioid use, addressing the challenges associated with opioid therapy in diverse patient populations.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| nalbuphine | Experimental | Drug: Nalbuphine Injection, Genetic: Next Generation Sequencing, Genetic: whole exome sequencingGiven as intravenously, 0.1-0.2 mg / kg at induction and intermittently |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nalbuphine InjectionAnaesthesia 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. | Drug | nalbuphine |
| Next Generation SequencingAlso: NGS, whole exome sequencing, sanger's technique5ml 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 | Genetic | nalbuphine |
| whole exome sequencingAlso: NGS, next generation sequencingOnly 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 | Genetic | nalbuphine |
Primary outcome
pain score
Time frame: 24 hours postoperatively
Zero is equivalent to no pain and 10 indicates the worst possible pain
3 secondary outcomes
sedation score
Time frame: 24 hours
nausea vomiting score
Time frame: 24 hours postoperatively
rescue analgesia
Time frame: 24 hours postoperatively
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2026.
- Results publication: PubMed 28409480Agarwal 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.
- Individual participant dataSharing planned: Yes. only IPD used in the results publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Talat Mirza, FCPS PhD study director
Ziauddin University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Nalbuphine Injection, Next Generation Sequencing and whole exome sequencing in people with Cholecystectomy and Hernia, Abdominal, run by Dr. Asma Abdus Salam at 1 site in Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Asma Abdus Salam, FCPS, MCPS, MBBS (+923002122264, asma.salam.azhar@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pain score (time frame: 24 hours postoperatively). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06996561, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2026.