Propofol-Enhanced Assessment of Ketamine for Chronic Pain and Depression (PEAK)

Randomized Double-blind Placebo-controlled Trial of Ketamine Given During Propofol Sedation in Patients With Chronic Pain and Depression

The goal of this clinical trial is to compare ketamine to a placebo when given as a single infusion during sedation in adults with chronic pain and depression. This study aims to:

• Evaluate whether ketamine is more effective than a placebo in treating chronic pain and depression
• Confirm that propofol sedation is a safe way to keep participants blinded to treatment
• Assess patients' comfort with the sedation process to improve future studies
• Explore whether patient expectations affects their pain and depression

Participants will:

• Need to qualify for the study based on stringent medical criteria
• Undergo sedation with propofol
• Randomly receive either a ketamine or a placebo (saline) infusion during sedation
• Complete several study assessments over 5-7 weeks

Study Overview

• Status: Not yet recruiting
• Conditions: Depression; Chronic Pain
• Intervention / Treatment: Drug: Ketamine; Drug: Normal saline

Detailed Description

Ketamine is a dissociative anesthetic that has been in clinical use for more than 50 years. In addition to its well-known anesthetic and pain-relieving properties, ketamine has repeatedly been found to have fast-acting antidepressant effects in patients with depression. However, the mechanisms underlying ketamine's ability to treat chronic pain and depression are poorly understood. A most basic question regarding ketamine's therapeutic mechanism is still unresolved: do patients need to consciously experience ketamine's acute dissociative effects to receive lasting analgesic and antidepressant benefits? In this clinical trial, participants will receive either ketamine or a placebo when they are under sedation with propofol.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Theresa Lii, MD, MS; Phone Number: 650-264-9442; Email: tlii@stanford.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 to 70 years old
• Comfortable speaking and writing in English
• Chronic pain present for at least 3 months
• Currently experiencing depression
• Able to comply with the study protocol and communicate with study personnel about adverse events and other clinically important information

Exclusion Criteria:

• Pregnant or breastfeeding
• One or more health conditions that makes study unsafe or unfeasible, determined by study physicians
• Regular use of medications that may have problematic interactions with the study drugs
• Participating in another clinical trial which may conflict with this one

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ketamine; A one-time intravenous infusion of ketamine (0.5 mg/kg)	Drug: Ketamine; 0.5 mg/kg ketamine infused intravenously over 40 minutes; Other Names: Ketalar
Placebo Comparator: Saline; A one-time intravenous infusion of normal saline	Drug: Normal saline; 0.9% normal saline infused intravenously over 40 minutes; Other Names: 0.9% NaCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity (past 24 hours)	A numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain) over the past 24 hours will be used to assess pain intensity.	screening; 7, 14, 21 and 28 days after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depression severity	The 21-item Beck Depression Inventory-II (BDI-II) assesses the severity of depressive symptoms experienced over the past 1 week. Items are self-rated on a 4-point scale. Higher total scores indicate greater depression symptom severity.	screening; immediately before the intervention; 7, 14, 21 and 28 days after treatment
Pain Intensity (current)	A numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain) assessing current pain	immediately before the intervention; immediately after the intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and severity of adverse events related to sedation	Adverse events (AEs) will be assessed through a combination of patient self-report, interviews by study staff, and surveillance of medical records by the research team. AEs will be graded by severity (1=mild, 2=moderate, 3=severe, 4=life threatening, and 5=death) and relatedness to the intervention (0=definitely unrelated, 1=unlikely, 2=possibly related, 3=probably related, 4 definitely related).	during the intervention; immediately after the intervention; 7, 14, 21 and 28 days after treatment
Proportion of participants who accurately recall intra-sedation events	Participants will be interviewed by study staff using the modified Brice Questionnaire, a set of questions asked in sequence to determine if the participant remembers anything between the time of induction and their awakening.	immediately after the intervention
Treatment guess	Participants will be asked to guess their assigned treatment in a forced binary choice and to rate their level of confidence on a scale from 0 to 100%. They will also be asked to provide reasons for their guess.	immediately after the intervention; 28 days after treatment
Treatment expectancies	The Stanford Expectations of Treatment Scale (SETS) measures the extent of positive and negative treatment expectancies. Participants are asked to rate their agreement with 6 brief statements on a 7-point scale ranging from 1 ("Strongly Disagree") to 7 ("Strongly Agree"). Higher scores correspond to stronger expectancies.	screening; immediately after the intervention
Pain interference	The 6-item PROMIS Pain Interference Short Form assesses the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. Items are self-rated on a 5-point scale ranging from 1 ("Not at all") to 5 ("Very Much"). Raw score totals are converted to standardized T-scores, with a higher T-score representing greater pain interference.	screening; immediately before the intervention; 7, 14, 21 and 28 days after treatment
Physical function	The 6-item PROMIS Physical Function Short Form assesses the ability to carry out physical tasks and activities in one's daily life. Items are self-rated on a 5-point scale ranging from 1 ("Unable to do") to 5 ("Without any difficulty"). Raw score totals are converted to standardized T-scores, with a higher T-score representing better physical function.	screening; immediately before the intervention; 7, 14, 21 and 28 days after treatment
Number of painful body regions	The CHOIR Body Map is a visual tool that allows individuals to indicate the location(s) of their pain on a human body outline.	screening; immediately before the intervention; immediately after the intervention; 7, 14, 21 and 28 days after treatment
Change in pain medication utilization	Participants are asked to rate how their pain medication usage has changed compared to before treatment	7, 14, 21 and 28 days after treatment
Pressure pain threshold	A pressure algometer device applied to the upper trapezius muscle will measure the pressure pain threshold by applying a controlled, gradually increasing force until the participant reports pain.	screening; immediately after the intervention
Enrollment rate	The total number of consented, eligible participants enrolled by the end of the study divided by the amount of time between date of opening enrollment and the date of consent from the last participant.	from date of opening enrollment to the date of consent from the last participant, assessed up to 60 months
Consent fraction	The proportion of patients who are contacted by study staff for recruitment who provide written informed consent to study procedures.	from date of opening enrollment to the date of consent from the last participant, assessed up to 60 months
Participant Experience Survey	Participants are asked at the end of the study to rate their experience with study procedures and to provide feedback for improvement.	through study completion, an average of 4 weeks

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Theresa Lii, MD, MS, Stanford University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: February 27, 2024
• First Submitted That Met QC Criteria: March 11, 2024
• First Posted (Actual): March 19, 2024

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Depression; Chronic Pain; Ketamine; Sedation; Propofol; Psychotropic Drugs; Hypnotics and Sedatives; Dissociative Anesthetics
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Pain; Neurologic Manifestations; Depression; Depressive Disorder; Chronic Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 73487

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified participant data, study outcomes, and data dictionaries
• IPD Sharing Time Frame: Available upon request after publication of the trial's primary findings for up to 5 years.
• IPD Sharing Access Criteria: Researchers must submit a brief proposal and statistical analysis plan for review and approval by the investigators and execute a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

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.: Yes