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

NCT ID: NCT06767566

Last Updated: 2025-04-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-28
• Study Completion Date: 2028-03-31

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).

Conditions

Pain; Postpartum Depression

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Ketamine Infusion: Cesarean Delivery Population

Loading dose infusion for 1 hour followed immediately by maintenance dose infusion for 11 hours.

Group Type: EXPERIMENTAL

Ketamine (Ketalar)

Intervention Type: DRUG

Loading Dose: 0.18 mg/kg/hr x 1 hour; Maintenance Dose 0.05 mg/kg/hr x 11 hours

Ketamine Infusion: Healthy Control Population

Loading dose infusion for 1 hour followed immediately by maintenance dose infusion for 11 hours.

Group Type: EXPERIMENTAL

Ketamine (Ketalar)

Intervention Type: DRUG

Loading Dose: 0.18 mg/kg/hr x 1 hour; Maintenance Dose 0.05 mg/kg/hr x 11 hours

Interventions

Ketamine (Ketalar)

Loading Dose: 0.18 mg/kg/hr x 1 hour; Maintenance Dose 0.05 mg/kg/hr x 11 hours

Intervention Type: DRUG

Other Intervention Names

0.18 mg/kg/1hr loading dose Ketamine

Eligibility Criteria

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.

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

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

• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Grace Lim, MD, MS

OTHER

Sponsor Role: lead

Responsible Party

Grace Lim, MD, MS

Associate Professor, Chief Obstetric & Women's Anesthesiology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Grace Lim, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

Magee Womens Hospital of UPMC

Pittsburgh, Pennsylvania, United States

Site Status: RECRUITING

UPMC Montefiore Clinical and Translational Research Center

Pittsburgh, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Amy Monroe, MPH, MBA

Role: CONTACT

monroeal@upmc.edu

4126236382

Alexandra Anderson, BS

Role: CONTACT

andersonah2@upmc.edu

4126414154

Facility Contacts

Amy Monroe, MPH, MBA

Role: primary

monroeal@upmc.edu

412-623-6382

Alexandra Anderson, BS

Role: backup

andersonah2@upmc.edu

412-641-4154

Amy Monroe, MPH, MBA

Role: primary

monroeal@upmc.edu

412-623-6382

Alexandra Anderson, BS

Role: backup

andersonah2@upmc.edu

412-641-4154

Other Identifiers

R01MH134538

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY22100019

Identifier Type: -

Identifier Source: org_study_id