Ketamine Pharmacokinetics and Pharmacodynamics for Postpartum Depression and Pain After Cesarean Delivery

Phase 1

Recruiting

• Conditions: Pain; Postpartum Depression
• Interventions: Drug: Ketamine (Ketalar)

• Registration Number: NCT06767566
• Lead Sponsor: Grace Lim, MD, MS

Brief Summary

The purpose of this study is to identify pharmacokinetics of postpartum ketamine infusion. This study will assess ketamine kinetics and metabolism in this setting. Ketamine is expected to exert different kinetics during the physiologic state of post-pregnancy. The goal in conducting this study is to better understand the pharmacokinetics and pharmacodynamics of postpartum ketamine infusion. A secondary goal is to compare these kinetics to reproductive age matched controls and to assess sex differences in ketamine pharmacokinetics.

The peripartum group of this study will receive ketamine after cesarean delivery, while the control group will consist of non-pregnant female subjects and male subjects receiving the same infusion protocol.

Detailed Description

A lack of data on new pain treatments in pregnancy puts 1.2 million US women having cesarean delivery (CD) every year at risk for poor pain control, depressed mood, and poor recovery. Evidence of successful post-surgical pain management and rapid reduction of depressive symptoms render ketamine a great candidate for post-CD pain management and potential reduction of postpartum depression (PPD) symptomology. Knowledge gaps in ketamine pharmacokinetics (PK) in the postpartum period limit an informed approach to its use for postpartum analgesia and PPD mitigation strategies. Similarly, knowledge gaps about sex differences in ketamine PK limit understandings about potential heterogeneity of treatment effects. This study aims to better understand the pharmacokinetics and pharmacodynamics of ketamine in postpartum women. Secondarily, it will assess key differences in postpartum ketamine PK compared to non-pregnant female controls. Secondarily it will assess key sex differences in ketamine metabolism between male and female subjects.

Peripartum females undergoing cesarean delivery will receive a ketamine infusion for 12 hours after cord clamping. Samples will be taken to characterize ketamine PK (primary objective). Healthy volunteer control females and males will receive the same ketamine infusion dosing schematic. Comparisons will be made between peripartum females and non-pregnant female controls, and between female and male controls (secondary objectives).

Study Timeline

• Study First Submitted: 2024-11-21
• Study First Submitted QC: 2025-01-08
• Study First Posted: 2025-01-10
• Study Start: 2025-03-28
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-14
• Last Update Posted: 2025-04-17
• Primary Completion: 2027-12-07
• Study Completion: 2028-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ketamine Infusion: Cesarean Delivery Population	Ketamine (Ketalar)	Loading dose infusion for 1 hour followed immediately by maintenance dose infusion for 11 hours.
Ketamine Infusion: Healthy Control Population	Ketamine (Ketalar)	Loading dose infusion for 1 hour followed immediately by maintenance dose infusion for 11 hours.

Primary Outcome Measures

Name	Time	Method
Maternal ketamine area under the curve (AUC)	0 to 24 hours from initiation of ketamine infusion	Ketamine area under the plasma concentration-time curve (AUC 0-∞) (AUC, mcg\*min/mL), which reflects the actual body exposure to ketamine after administration of ketamine.

Secondary Outcome Measures

Name	Time	Method
Patient reported acceptability of any reported side effects	0 to 24 hours after initiation of ketamine infusion	Proportion (%) of patient cohort reporting acceptability of ketamine infusion
Pain area under the curve (AUC)	0 to 24 hours after initiation of ketamine infusion	Pain score area under the curve (AUC) where pain scores are measured from 0 (no pain) to 10 (worst imaginable pain), for the duration of epidural analgesia.
Depression scores (Peripartum)	Baseline to week 12 post-infusion	Depression scores as defined by the Edinburgh Postnatal Depression Scale (Peripartum Group), scale 0-30, measured among the peripartum cohort.
Depression Scores (control)	Baseline to week 12 post-infusion	Depression scores as defined by the Patient Health Questionnaire (PHQ-9) (Control Group), scale 0-27, measured among the control nonperipartum cohort.

Trial Locations

Locations (4)

Magee Womens Hospital of UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC Montefiore Clinical and Translational Research Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Magee Womens Hospital of UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC Montefiore Clinical and Translational Research Center; 🇺🇸 Pittsburgh, Pennsylvania, United States