Preoperative Genotyping for Cesarean Section Complications

(PPAP C-Section Trial)

Recruiting at 1 trial location

Overseen By Carly Riedmann, MPH

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Senthilkumar Sadhasivam

Disqualifiers: Uncontrolled diabetes, Hypertension, Opioid misuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 days

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for managing pain in mothers undergoing planned C-sections. It uses a personalized approach to pain relief, aiming to make opioid use safer for both mothers and their babies. Participants will undergo genetic testing (Preoperative Genotyping) to tailor pain management and reduce opioid-related risks. Women planning an elective C-section and willing to use opioids for pain relief may be suitable candidates. As an unphased trial, this study allows participants to contribute to innovative pain management strategies that could enhance safety for mothers and their babies.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have uncontrolled diabetes, hypertension, or a history of opioid misuse, you may not be eligible to participate.

What prior data suggests that the Personalized Perioperative Analgesia Platform (PPAP) is safe for mothers and infants?

Research has shown that the Personalized Perioperative Analgesia Platform (PPAP) customizes pain management using each person's genetic information. This method aims to improve pain relief and reduce the potential negative effects of opioid use for mothers and their babies during and after a C-section.

Although specific study results on the safety of PPAP are not yet available, its focus on personalization suggests it could lead to better outcomes. Researchers are testing PPAP to ensure it is safe and minimizes any side effects. As this trial is in its early stages, it primarily focuses on testing safety and effectiveness, so detailed safety data is not yet available. However, the trial aims to ensure safety for both mothers and their babies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Personalized Perioperative Analgesia Platform (PPAP) because it tailors pain management for mothers undergoing cesarean sections using genetic information. Unlike standard pain management options, which typically involve a one-size-fits-all approach with medications like oxycodone, PPAP aims to optimize pain relief by customizing analgesic plans based on an individual's genetic makeup. This approach has the potential to enhance pain control while minimizing side effects, improving recovery experiences for mothers.

What evidence suggests that the Personalized Perioperative Analgesia Platform (PPAP) is effective for improving analgesia in breastfeeding mothers undergoing Cesarean sections?

Research has shown that the Personalized Perioperative Analgesia Platform (PPAP), which participants in this trial may receive, could help manage pain for mothers during cesarean sections. This method uses genetic information to customize pain treatment for each person. By doing so, it might reduce the need for opioids, which can have serious side effects for both mothers and their babies. Early findings suggest that certain genetic factors affect how patients feel and handle pain after surgery. While more detailed information on its effectiveness is still being gathered, personalized care could lead to better results and less pain overall. ^{1 3 4 6 7}

Who Is on the Research Team?

Senthilkumar Sadhasivam, MD, MPH

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for adult women over 18, of any race, with a physical status suitable for elective Cesarean section (ASA 1-3), who plan to use opioids post-surgery and intend to breastfeed. It excludes those with severe preoperative pain or opioid misuse, allergies to oxycodone, liver disease, renal issues, multiple gestations, expected non-viable births or serious neonatal conditions.

Inclusion Criteria

I am an adult woman planning a C-section and open to using opioids for pain.

Exclusion Criteria

Allergy to oxycodone

Any history of opioid misuse before or during pregnancy as per self-report and clinical notes

I do not have major neurological, liver, or kidney diseases.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo genotyping and receive oxycodone dosing during and after Cesarean section

4 days

In-hospital stay

Follow-up

Participants are monitored for safety and effectiveness, including genetic factors and opioid dependence, up to 1 year post-surgery

1 year

Long-term monitoring

Participants complete psychological questionnaires to assess chronic pain and opioid dependence

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Personalized Perioperative Analgesia Platform (PPAP)
• Preoperative Genotyping

Trial Overview The study aims to develop a Personalized Perioperative Analgesia Platform (PPAP) that could improve pain management and reduce the adverse effects of opioids in new mothers and their babies after C-sections by using preoperative genotyping.

How Is the Trial Designed?

Group I: Mother undergoing planned Cesarean section Experimental Treatment 1 Intervention

Mother subject will have genotyping blood draw performed at the time of controlled delivery (CD). Blood samples and breast milk samples will also be taken during the oxycodone dosing schedule.

Group II: Infant Experimental Treatment 1 Intervention

Infant subject will have genotyping blood draw performed only at the time of controlled delivery (CD)

Who Is Running the Clinical Trial?

Senthilkumar Sadhasivam

Lead Sponsor

Trials

5

Recruited

3,200+

Senthil Sadhasivam

Lead Sponsor

Trials

7

Recruited

4,200+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

Genetic research in obstetrics and anesthesiology has focused on understanding how genetic variations affect issues like preterm labor and responses to anesthesia, but so far, these findings have had only modest effects on clinical practice.

Advancements in genetic technologies, such as whole exome sequencing and real-time genotyping, are expected to enhance the role of genetics in clinical decision-making in obstetrics over the next decade.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacogenetics in obstetric anesthesia. Landau, R., Smiley, R.[2018]

In a study of 266 patients undergoing elective cesarean delivery, the COMT rs4680 and μ-opioid receptor rs1799971 polymorphisms were not found to be associated with the development of chronic postsurgical pain (CPSP) three months after surgery.

However, the rs1799971 genotype influenced analgesic consumption, with patients carrying the GG genotype requiring more pain relief medication postoperatively, indicating a potential role in pain management rather than CPSP development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influences of COMT rs4680 and OPRM1 rs1799971 Polymorphisms on Chronic Postsurgical Pain, Acute Pain, and Analgesic Consumption After Elective Cesarean Delivery. Wang, L., Wei, C., Xiao, F., et al.[2020]

Genetic variations, particularly in the mu-opioid receptor gene, significantly influence how individuals perceive pain during labor and respond to pain relief medications after cesarean deliveries.

There is emerging evidence that certain genetic profiles may increase the risk of developing persistent pain after cesarean sections, highlighting the potential for personalized pain management strategies in obstetric anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacogenetics in obstetric anesthesia. Landau, R., Kraft, JC.[2020]

In a study of 190 labor participants and 103 cesarean delivery participants, the OPRM1:c.304A>G genetic polymorphism did not significantly affect the duration of intrathecal fentanyl analgesia or the need for supplemental analgesics after intrathecal morphine, indicating that this genetic variation may not influence opioid effectiveness in these settings.

However, individuals with the 304A homozygous genotype experienced a higher incidence of pruritus, suggesting that while the genetic variant may not alter pain management outcomes, it could affect side effects related to opioid use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Observational study of the effect of mu-opioid receptor genetic polymorphism on intrathecal opioid labor analgesia and post-cesarean delivery analgesia. Wong, CA., McCarthy, RJ., Blouin, J., et al.[2013]

In a study of 55 Portuguese women undergoing elective cesarean sections, it was found that variations in the CYP2D6 gene significantly affect pain perception, with 9% classified as poor metabolizers and showing increased pain levels.

The research suggests that reduced activity of CYP2D6 may lead to decreased metabolism of pain-related substances, indicating that genotyping for CYP2D6 could help tailor opioid dosing for better pain management and fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CYP2D6 Pharmacogenetics Testing and Post-Cesarean Section Pain Scores-a Preliminary Study. Ribeiro, C., Quinta, R., Raposo, A., et al.[2020]

In a study of 973 patients undergoing total hysterectomy, those with the OPRM1 118G allele reported higher postoperative pain scores and used more morphine compared to those with the 118A allele, indicating a genetic influence on pain perception and opioid requirements.

The research found no significant association between OPRM1 genotype and preoperative pressure pain threshold or tolerance, suggesting that while genetics play a role in postoperative pain and morphine use, they may not affect baseline pain sensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of mu-opioid receptor variant on morphine use and self-rated pain following abdominal hysterectomy. Sia, AT., Lim, Y., Lim, EC., et al.[2022]

Opioids are commonly used for pain relief during the perioperative period, but their effectiveness varies greatly among individuals due to factors like age, sex, race, and genetic differences, which can lead to inadequate pain relief or serious side effects.

Personalizing opioid analgesia based on genetic and nongenetic factors could enhance pain management and reduce adverse effects, but more extensive and well-structured studies are needed to validate these approaches and develop practical clinical tools for individualized treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacogenomics of opioids and perioperative pain management. Sadhasivam, S., Chidambaran, V.[2021]

The study of 98 women prescribed codeine after cesarean sections found that genetic variations in the OPRM1 and UGT2B7 genes significantly influenced codeine consumption, indicating a need for personalized pain management strategies.

Maternal age and ethnicity also affected codeine requirements, with older mothers and Asian women needing higher doses, highlighting the importance of considering individual factors in pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacogenetics of codeine pain relief in the postpartum period. Baber, M., Chaudhry, S., Kelly, L., et al.[2020]

In a study of 161 women undergoing elective cesarean delivery, the A118G polymorphism of the opioid receptor did not affect the amount of epidural analgesia (sufentanil plus ropivacaine) needed in the first 24 hours post-surgery.

Patient satisfaction, pain scores, and adverse effects were similar across different genetic groups (AA, AG, GG), indicating that the A118G polymorphism does not influence the efficacy or safety of the analgesic regimen used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid receptor A118G polymorphism does not affect the consumption of sufentanil and ropivacaine by patient-controlled epidural analgesia after cesarean section. Xu, GH., Gao, M., Sheng, QY., et al.[2018]

The A118G single nucleotide polymorphism of the µ-opioid receptor significantly influences pain relief and the amount of fentanyl needed for effective analgesia in women after a caesarean section, as shown in a study of 96 patients.

Patients with the GG genotype required higher doses of fentanyl and reported greater pain scores compared to those with the AA and AG genotypes, indicating that G118 homozygotes have a poorer response to fentanyl.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Human µ-opioid receptor A118G polymorphism affects epidural patient-controlled analgesia with fentanyl]. Zhang, S., Li, S., Tan, X.[2013]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05380531

Personalized Perioperative Analgesia Platform (PPAP) for ... The purpose of this collaborative CTSA (Clinical and Translational Science Award) application is to develop an innovative perioperative precision analgesia ...

2. clinicaltrial.be clinicaltrial.be/en/details/17033?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Personalized Perioperative Analgesia Platform (PPAP) for... Personalized Perioperative Analgesia Platform (PPAP) for Cesarean Section ... outcomes in women undergoing a cesarean section and their infant.

3. withpower.com withpower.com/trial/phase-opioids-use-5-2022-b2eaa

Preoperative Genotyping for Cesarean Section ... The Personalized Perioperative Analgesia Platform (PPAP) is unique because it uses genetic information to tailor pain management specifically for each patient ...

4. research-studies.allinforhealth.info research-studies.allinforhealth.info/us/en/listing/12382/personalized-perioperative-analgesia-platform/

Personalized Perioperative Analgesia Platform (PPAP) for ... Clinical Studies for Cesarean Section Complications | Opioid Use , Personalized Perioperative Analgesia Platform (PPAP) for Cesarean Section.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959289X18305740

Personalized analgesic management for cesarean delivery The overall accuracy of the model was 56%. Certain patient and procedural factors were associated with higher levels of reported postoperative pain. Patients ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05380531/personalized-perioperative-analgesia-platform-ppap-for-cesarean-section

Personalized Perioperative Analgesia Platform (PPAP) for ... The purpose of this collaborative CTSA (Clinical and Translational Science Award) application is to develop an innovative perioperative ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7921280/

Enhanced Recovery After Cesarean: Current and Emerging ... Enhanced recovery after cesarean delivery (ERAC) provides an evidenced-based system to improve maternal outcomes, functional recovery, maternal-infant bonding, ...