The Pharmacokinetics of Ketamine in the Breast Milk of Lactating Women (KRF-LAC)

• ClinicalTrials.gov Identifier: NCT04285684
• Recruitment Status: Completed
• First Posted: February 26, 2020
• Results First Posted: December 13, 2021
• Last Update Posted: December 13, 2021
• Sponsor: The Ketamine Research Foundation
• Information provided by (Responsible Party): The Ketamine Research Foundation

Tracking Information

• First Submitted Date: February 24, 2020
• First Posted Date: February 26, 2020
• Results First Submitted Date: September 8, 2021
• Results First Posted Date: December 13, 2021
• Last Update Posted Date: December 13, 2021
• Actual Study Start Date: December 20, 2019
• Actual Primary Completion Date: January 5, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 10, 2021)

• Ketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of .5mg/kg Ketamine [ Time Frame: 3, 6, 9, and 12 hour collections ]
  Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 3, 6, 9, and 12 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
• Ketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of 1mg/kg Ketamine [ Time Frame: 3, 6, 9, and 12 hour collections ]
  Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 3, 6, 9, and 12 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
• Norketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of .5mg/kg Ketamine [ Time Frame: 3, 6, 9, and 12 hour collections ]
  Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 3, 6, 9, and 12 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
• Norketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of 1mg/kg Ketamine [ Time Frame: 3, 6, 9, and 12 hour collections ]
  Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 3, 6, 9, and 12 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
• Dehydronorketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of .5mg/kg Ketamine [ Time Frame: 3, 6, 9, and 12 hour collections ]
  Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 3, 6, 9, and 12 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
• Dehydronorketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of 1mg/kg Ketamine [ Time Frame: 3, 6, 9, and 12 hour collections ]
  Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 3, 6, 9, and 12 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
• Hydroxynorketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of .5mg/kg Ketamine [ Time Frame: 3, 6, 9, and 12 hour collections ]
  Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 3, 6, 9, and 12 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
• Hydroxynorketamine Concentration in Breast Milk, up to 12 Hours at 3 Hour Intervals, Following an IM Administration of 1mg/kg Ketamine [ Time Frame: 3, 6, 9, and 12 hour collections ]
  Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 3, 6, 9, and 12 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
• Ketamine Concentration in Breast Milk at 24 and 30 Hours After an IM Administration of 1mg/kg Ketamine [ Time Frame: 24 and 30 hour collections ]
  Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 24 and 30 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
• Norketamine Concentration in Breast Milk at 24 and 30 Hours After an IM Administration of 1mg/kg Ketamine [ Time Frame: 24 and 30 hour collections ]
  Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 24 and 30 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
• Dehydronorketamine Concentration in Breast Milk at 24 and 30 Hours After an IM Administration of 1mg/kg Ketamine [ Time Frame: 24 and 30 hour collections ]
  Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 24 and 30 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng
• Hydroxynorketamine Concentration in Breast Milk at 24 and 30 Hours After an IM Administration of 1mg/kg Ketamine [ Time Frame: 24 and 30 hour collections ]
  Quantitative analysis of the concentration of ketamine and its metabolites in breast milk (collected by pumping breast milk into containers at 24 and 30 hours post ketamine IM administration) was performed at the Clinical Medicine and Toxicology Laboratory at UCSF School of Medicine. Sample aliquots were frozen in our conventional freezer at the clinic where the sessions took place, labelled with a HIPAA compliant code which blinded the lab to all patient data. The limits of sensitivity for the quantification of each substance were: Ketamine: 0.25 ng Norketamine: 0.25 ng Dehydronorketamine: 0.1 ng Hydroxynorketamine: 0.25 ng

Original Primary Outcome Measures (submitted: February 24, 2020)

The Pharmacodynamics of Ketamine in the Breast Milk of Lactating Women: [ Time Frame: 12-24 hours at 3 hour intervals ]

Assessing the concentration of ketamine in breast milk

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Pharmacokinetics of Ketamine in the Breast Milk of Lactating Women
• Official Title: The Pharmacokinetics of Ketamine in the Breast Milk of Lactating Women: Quantification of Ketamine and Metabolites
• Brief Summary: Quantification of Ketamine in Breast Milk at 3 hour Intervals up to 30 hours-- obtained from lactating women who receive 2 different Intramuscular injections of ketamine on two separate days at least 5 days apart.

Detailed Description

Quantification of Ketamine in Breast Milk at 3 hour Intervals up to 30 hours-- obtained from lactating women who receive 2 different Intramuscular injections of ketamine on two separate days at least 5 days apart: 0.5mg/kg and 1.0mg kg.

Women are required to have been breast feeding for at least 3 months and be healthy and on no medications. Support is provided for the entire time at the site and for any at home pumping. During the period of ketamine's influence, subjects are reclining and with 2 Investigators. The initial subject's data will determine the length of time for pumping--most likely 12 hours as ketamine and the active principle metabolite have half-lives of less than 3 hours. Determination of concentration of ketamine in breast milk is being done at the UCSF Clinical lab with quantification of metabolites that are inactive as well. This research is of benefit by providing lactating women information on potential exposure of infants/children to ketamine. It will serve as a guide as KRF conducts research on postpartum depression and for women at large using ketamine for psychiatric indications.

• Study Type: Interventional
• Study Phase: Early Phase 1

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

4 subjects receiving 0.5mg/kg and 1.0mg/kg of ketamine at least 5 days apart with collection of breast milk by pumping at 3 hour intervals

Masking: None (Open Label)
Primary Purpose: Basic Science

Condition

• Ketamine
• Lactation

Intervention

Drug: ketamine in lactation

2 dose IM by weight and assessing concentrations of ketamine in expressed milk at intervals

Other Name: Assessing concentration of ketamine in breast milk at intervals

Study Arms

Ketamine, lactation

Lactating women--4 subjects, 2 dosage format: ketamine 0;5mg/kg and 1.0mg/kg IM at least 5 days apart.

Intervention: Drug: ketamine in lactation

Publications *

• Chang T, Glazko AJ. Biotransformation and disposition of ketamine. Int Anesthesiol Clin. 1974 Summer;12(2):157-77. doi: 10.1097/00004311-197412020-00018. No abstract available.
• Clements JA, Nimmo WS, Grant IS. Bioavailability, pharmacokinetics, and analgesic activity of ketamine in humans. J Pharm Sci. 1982 May;71(5):539-42. doi: 10.1002/jps.2600710516.
• Dore J, Turnipseed B, Dwyer S, Turnipseed A, Andries J, Ascani G, Monnette C, Huidekoper A, Strauss N, Wolfson P. Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data and Outcomes in Three Large Practices Administering Ketamine with Psychotherapy. J Psychoactive Drugs. 2019 Apr-Jun;51(2):189-198. doi: 10.1080/02791072.2019.1587556. Epub 2019 Mar 27.
• Little B, Chang T, Chucot L, Dill WA, Enrile LL, Glazko AJ, Jassani M, Kretchmer H, Sweet AY. Study of ketamine as an obstetric anesthetic agent. Am J Obstet Gynecol. 1972 May 15;113(2):247-60. doi: 10.1016/0002-9378(72)90774-0. No abstract available.
• Wan LB, Levitch CF, Perez AM, Brallier JW, Iosifescu DV, Chang LC, Foulkes A, Mathew SJ, Charney DS, Murrough JW. Ketamine safety and tolerability in clinical trials for treatment-resistant depression. J Clin Psychiatry. 2015 Mar;76(3):247-52. doi: 10.4088/JCP.13m08852.
• Weber F, Wulf H, Gruber M, Biallas R. S-ketamine and s-norketamine plasma concentrations after nasal and i.v. administration in anesthetized children. Paediatr Anaesth. 2004 Dec;14(12):983-8. doi: 10.1111/j.1460-9592.2004.01358.x.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 24, 2020): 4
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: January 5, 2021
• Actual Primary Completion Date: January 5, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:• Age 21-45

• Postpartum with established lactation for a minimum of 3 months.
• Ability to pump breast milk and to provide a reservoir for infant feeding prior to the study; or acceptance of bottle feeding by the infant.
• In good health-normal BP/P; afebrile-temp ascertained; review of systems by MD; absence of diagnosed illnesses.
• Not pregnant--Pregnancy tested for before each administration by urine assay.

Exclusion Criteria:• Hypertension with a BP greater than 145/90

• Subjects must be off all psychiatric medications specifically; medications and supplements, or evaluated by the PI for non-interference
• No alcohol or other substances such as marijuana for 72 hours or more.
• Weight <50kg or > 90kg.
• Pregnancy

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes

• Ages: 21 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04285684
• Other Study ID Numbers: KetamineResearch
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Publication of data in peer reviewed journal including all data; and available from KRF by request
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: 6 months to 1 year
• Access Criteria: Public and researchers Health care professionals
• URL: http://www.ketamineresearchfoundation.com

• Current Responsible Party: The Ketamine Research Foundation
• Original Responsible Party: Same as current
• Current Study Sponsor: The Ketamine Research Foundation
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Philip E Wolfson, MD; Ketamine Research Foundation

• PRS Account: The Ketamine Research Foundation
• Verification Date: October 2021