Ketamine Pharmacokinetics and Pharmacodynamics for Postpartum Depression and Pain After Cesarean Delivery (PREPARE-2)

June 24, 2026 updated by: Grace Lim, University of Utah

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.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Magee Womens Hospital of UPMC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Peripartum Participants:

Inclusion Criteria

  • Cesarean delivery
  • Adults 18 years and older
  • Term delivery ≥ 37 weeks gestation anticipated at time of delivery
  • ASA PS 2 or 3
  • Able to provide informed consent
  • One of the following must be met for inclusion: Not planning to breastfeed OR ketamine use indicated for pain management plan.

Exclusion Criteria

  • Patient going under general anesthesia for cesarean delivery
  • Allergy to study medication (ketamine)
  • ASA PS 4 +
  • Contraindications to neuraxial anesthesia
  • Preterm delivery (<37 weeks gestation)
  • Anticipated fetal-neonatal complex care plan as indicated in the patient's chart
  • Patient history of ketamine or PCP abuse
  • Patient history of schizophrenia or psychosis
  • Patient history of liver or renal insufficiency
  • Patient history of uncontrolled hypertension, chest pain, arrhythmia, head trauma, or intracranial hypertension, uncontrolled hyperthyroidism, or other contraindications to ketamine
  • Participating in another pain or depression intervention trial
  • Undergoing hormonal or gender affirming therapies
  • Pre-eclampsia with severe features
  • Hemodynamic instability
  • Inability to participate in study procedures for any reason
  • Contraindicated medications use: oral antihypertensive medications (exclusion: hypertensive disorders of pregnancy), intravenous magnesium (exclusion: pre-eclampsia with severe features), ketamine/phencyclidine/psilocybins/any other psychedelics (exclusion: ketamine or PCP abuse), lithium/valproate/carbamazepine/lamotrigine/haloperidol/chlorpromazine/fluphenazine/aripiprazole/clozapine/other typical or atypical antipsychotic medications (exclusion: schizophrenia or psychosis)

Control Participants

Inclusion Criteria

  • Age 18 years and older
  • Sex: Male or Female
  • Able to provide informed consent
  • ASA PS 1, 2, or 3

Exclusion Criteria

  • Allergy to study medication (ketamine)
  • ASA PS 4 +
  • Inability to participate in study procedures for any reason
  • Patient history of ketamine or PCP abuse
  • Patient history of schizophrenia or psychosis
  • Patient history of liver or renal insufficiency
  • Patient history of uncontrolled hypertension, chest pain, arrhythmia, head trauma, intracranial hypertension, uncontrolled hyperthyroidism, or other contraindications to ketamine
  • Participating in another pain or depression intervention trial
  • Hemodynamic instability
  • Pregnant or pregnant within the last 6 weeks
  • Unwilling to provide urine sample for pregnancy testing (female controls)
  • Undergoing hormonal or gender affirming therapies
  • Contraindicated medications use: ketamine, phencyclidine, psilocybins, or other psychedelics (exclusion: ketamine or PCP abuse), lithium/valproate/carbamazepine/lamotrigine/haloperidol/chlorpromazine/fluphenazine/aripiprazole/clozapine, or other typical or atypical antipsychotic medications (exclusion: schizophrenia or psychosis)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ketamine Infusion: Cesarean Delivery Population
Loading dose infusion for 1 hour followed immediately by maintenance dose infusion for 11 hours.
Drug: Ketamine (Ketalar)
Loading Dose: 0.18 mg/kg/hr x 1 hour; Maintenance Dose 0.05 mg/kg/hr x 11 hours
Other Names:
  • 0.18 mg/kg/1hr loading dose Ketamine
Experimental: Ketamine Infusion: Healthy Control Population
Loading dose infusion for 1 hour followed immediately by maintenance dose infusion for 11 hours.
Drug: Ketamine (Ketalar)
Loading Dose: 0.18 mg/kg/hr x 1 hour; Maintenance Dose 0.05 mg/kg/hr x 11 hours
Other Names:
  • 0.18 mg/kg/1hr loading dose Ketamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maternal ketamine area under the curve (AUC)
Time Frame: 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.
0 to 24 hours from initiation of ketamine infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient reported acceptability of any reported side effects
Time Frame: 0 to 24 hours after initiation of ketamine infusion
Proportion (%) of patient cohort reporting acceptability of ketamine infusion
0 to 24 hours after initiation of ketamine infusion
Pain area under the curve (AUC)
Time Frame: 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.
0 to 24 hours after initiation of ketamine infusion
Depression scores (Peripartum)
Time Frame: 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.
Baseline to week 12 post-infusion
Depression Scores (control)
Time Frame: 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.
Baseline to week 12 post-infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Utah

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Grace Lim, MD, MSc, University of Utah

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 28, 2025

Primary Completion (Estimated)

December 7, 2027

Study Completion (Estimated)

March 1, 2028

Study Registration Dates

First Submitted

November 21, 2024

First Submitted That Met QC Criteria

January 8, 2025

First Posted (Actual)

January 10, 2025

Study Record Updates

Last Update Posted (Actual)

June 29, 2026

Last Update Submitted That Met QC Criteria

June 24, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY22100019
  • R01MH134538 (U.S. NIH Grant/Contract: National Institute of Mental Health)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Deidentified data will be available for public benefit and knowledge. Items for uploading will include clinical measures, patient reported outcomes, psychometric testing data, sensory testing data, and all PK data. Technical protocols and any other data collected under this project will be shared upon request to allow others to perform secondary analyses.

IPD Sharing Time Frame

Beginning with 3 months and ending at 5 years following article publication.

IPD Sharing Access Criteria

Researchers who propose a methodologically sound proposal may submit said proposals to limkg2@upmc.edu. To gain access to data, requestors will need to sign a data access agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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