search
Back to results

Ketamine and Midazolam Infusions for CRPS: Feasibility Study

Primary Purpose

Complex Regional Pain Syndromes

Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ketamine
Midazolam
Normal Saline
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Complex Regional Pain Syndromes focused on measuring Feasibility Study, Ketamine, Midazolam, Complex Regional Pain Syndrome, Active Placebo, Analgesics, Dissociative Anesthetics, Chronic Pain, Neuropathic Pain

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Age 18 to 65 years Meets the International Association for the Study of Pain (IASP) diagnostic criteria for complex regional pain syndrome (CRPS) Primary complaint of CRPS-attributable pain for ≥3 months Average pain intensity of ≥3/10 over the last month Can read and comprehend English-language questionnaires Can receive text messages by phone Can identify a responsible adult who can provide transportation to and from infusion site for 5 consecutive days (Mon-Fri)

Sites / Locations

  • Stanford University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ketamine and Midazolam

Midazolam and Saline

Arm Description

Participants will receive intravenous infusions of ketamine and midazolam for 4 hours each day, over 5 consecutive days, in an outpatient setting.

Participants will receive intravenous infusions of midazolam and normal saline for 4 hours each day, over 5 consecutive days, in an outpatient setting.

Outcomes

Primary Outcome Measures

Number and proportion of patients who can undergo the steps of recruitment, informed consent, enrollment, and randomization
Out of all patients identified as potentially eligible for the study based on chart review, we will measure the number and proportion who can undergo the steps of recruitment, informed consent, enrollment, and randomization during a 2-month period.
Number and proportion of randomized participants who remain in the study until the last follow-up timepoint
Out of all patients who were randomized to a treatment group, we will measure the number and proportion who remain in the study until their last follow-up timepoint.
Change in participant masking
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%.
Change in participant masking
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%.
Change in investigator masking
Investigators administering and monitoring the drug infusions will be asked to guess the participant's assigned treatment in a forced binary choice and to rate their level of confidence on a scale from 0 to 100%.
Change in investigator masking
Investigators administering and monitoring the drug infusions will be asked to guess the participant's assigned treatment in a forced binary choice and to rate their level of confidence on a scale from 0 to 100%.
Number and types of adverse events
Adverse events will be elicited from the participant in a brief, open-ended structured interview.

Secondary Outcome Measures

Pain intensity
A numerical rating scale ranging from 0 (no pain) to 10 (worst pain imaginable) over the past 24 hours will be used to assess pain intensity.
Treatment expectancies
The 6-item Healing Encounters and Attitudes Lists (HEAL) Short Form for Treatment Expectancy will be used to assess self-reported expectations about the study treatment. Participants are asked to rate their agreement with brief statements such as, "This treatment will be successful" and "I am confident in this treatment".
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.
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.
Depression (PROMIS)
The 6-item PROMIS Depression Short Form assesses the severity of depressive symptoms experienced by an individual. Items are self-rated on a 5-point scale ranging from 1 ("Never") to 5 ("Always"). Raw score totals are converted to standardized T-scores, with a higher T-score representing greater depression symptom severity.
Depression (PHQ-9)
The 9-item PHQ-9 will be used as an additional indicator for changes in depression symptom severity, and to monitor for any risk of acute suicidality during the trial (item #9: "Thoughts that you would be better off dead, or of hurting yourself"). Items are self-rated on a 4-point scale ranging from 0 ("Not at all") to 3 ("Nearly every day"). Higher total scores indicate greater depression symptom severity.
Anxiety
The 6-item PROMIS Anxiety Short Form assesses the severity of anxiety symptoms experienced by an individual. Items are self-rated on a 5-point scale ranging from 1 ("Never") to 5 ("Always"). Raw score totals are converted to standardized T-scores, with a higher T-score representing greater anxiety symptom severity.
Sleep disturbance
The 6-item PROMIS Sleep Disturbance Short Form assesses the severity of sleep-related issues, such as trouble falling asleep, staying asleep, and experiencing non-restorative sleep. 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 sleep disturbance.
Pain catastrophizing
The 13-item Pain Catastrophizing Scale assesses the extent to which an individual engages in magnifying, rumination, and helplessness thoughts related to their pain experience. Items are self-rated on a 5-point scale ranging from 0 ("Not at all") to 4 ("All the time"). Higher total scores indicates higher levels of pain catastrophizing.
Chronic pain acceptance
The 8-item Chronic Pain Acceptance Questionnaire assesses one's level of acceptance and willingness to engage in valued activities despite the presence of chronic pain. Items are self-rated on a 7-point scale ranging from 0 ("Never true") to 6 ("Always true"). Higher total scores indicate greater levels of chronic pain acceptance.
Patient global impression of change
The Patient Global Impression of Change scale assesses the patient's perception of change in their overall health status resulting from a specific treatment. The single-item scale is self-rated on a 7-point scale ranging from 1 ("Very much improved") to 7 ("Very much worse").
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.

Full Information

First Posted
June 26, 2023
Last Updated
October 6, 2023
Sponsor
Stanford University
search

1. Study Identification

Unique Protocol Identification Number
NCT05945147
Brief Title
Ketamine and Midazolam Infusions for CRPS: Feasibility Study
Official Title
Feasibility Study Comparing a Ketamine and Midazolam Infusion to a Midazolam-Only Infusion for Complex Regional Pain Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 15, 2023 (Anticipated)
Primary Completion Date
January 31, 2024 (Anticipated)
Study Completion Date
January 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study will assess the feasibility of administering ketamine plus midazolam or midazolam alone, when infused over 5 days in an outpatient setting, to adults with complex regional pain syndrome (CRPS).
Detailed Description
Subanesthetic ketamine infusions are a potentially impactful treatment for chronic refractory pain, but the acute psychoactive effects of ketamine complicate successful masking in randomized trials. Multi-day ketamine infusions have produced long-lasting, but not permanent, remission of symptoms in complex regional pain syndrome (CRPS), a chronic and often debilitating neuropathic pain condition that can affect one or more limbs. In this feasibility study, 4 adults with CRPS will be randomized to receive either ketamine and midazolam or midazolam-only, infused over 5 days in an outpatient setting. The objectives of this feasibility study are: Assess whether the recruitment and retention rate observed in this feasibility study can support a larger clinical trial. Evaluate whether participants can adhere to study procedures. Determine whether midazolam, when given alone as an intravenous (IV) infusion, can be used as an active placebo that is well-tolerated, practical, and believable compared to a ketamine plus midazolam infusion. Gather preliminary data on clinically-relevant outcomes for CRPS.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Complex Regional Pain Syndromes
Keywords
Feasibility Study, Ketamine, Midazolam, Complex Regional Pain Syndrome, Active Placebo, Analgesics, Dissociative Anesthetics, Chronic Pain, Neuropathic Pain

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
4 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ketamine and Midazolam
Arm Type
Experimental
Arm Description
Participants will receive intravenous infusions of ketamine and midazolam for 4 hours each day, over 5 consecutive days, in an outpatient setting.
Arm Title
Midazolam and Saline
Arm Type
Placebo Comparator
Arm Description
Participants will receive intravenous infusions of midazolam and normal saline for 4 hours each day, over 5 consecutive days, in an outpatient setting.
Intervention Type
Drug
Intervention Name(s)
Ketamine
Other Intervention Name(s)
Ketalar
Intervention Description
An escalating dose of ketamine (0.15 to 0.4 mg/kg/hr) will be administered as 4-hour infusions over 5 consecutive days
Intervention Type
Drug
Intervention Name(s)
Midazolam
Other Intervention Name(s)
Versed
Intervention Description
A constant dose of midazolam (0.04 mg/kg/hr) will be administered as 4-hour infusions over 5 consecutive days
Intervention Type
Drug
Intervention Name(s)
Normal Saline
Other Intervention Name(s)
0.9% Sodium Chloride
Intervention Description
An escalating dose of normal saline (0.15 to 0.4 mg/kg/hr) will be administered as 4-hour infusions over 5 consecutive days
Primary Outcome Measure Information:
Title
Number and proportion of patients who can undergo the steps of recruitment, informed consent, enrollment, and randomization
Description
Out of all patients identified as potentially eligible for the study based on chart review, we will measure the number and proportion who can undergo the steps of recruitment, informed consent, enrollment, and randomization during a 2-month period.
Time Frame
2 months after the study opens for enrollment
Title
Number and proportion of randomized participants who remain in the study until the last follow-up timepoint
Description
Out of all patients who were randomized to a treatment group, we will measure the number and proportion who remain in the study until their last follow-up timepoint.
Time Frame
8 weeks after receiving intervention
Title
Change in participant masking
Description
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%.
Time Frame
Daily during intervention administration (5 days), and once at 8 weeks after receiving intervention
Title
Change in participant masking
Description
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%.
Time Frame
During intervention administration
Title
Change in investigator masking
Description
Investigators administering and monitoring the drug infusions will be asked to guess the participant's assigned treatment in a forced binary choice and to rate their level of confidence on a scale from 0 to 100%.
Time Frame
8 weeks after receiving intervention
Title
Change in investigator masking
Description
Investigators administering and monitoring the drug infusions will be asked to guess the participant's assigned treatment in a forced binary choice and to rate their level of confidence on a scale from 0 to 100%.
Time Frame
During intervention administration
Title
Number and types of adverse events
Description
Adverse events will be elicited from the participant in a brief, open-ended structured interview.
Time Frame
8 weeks after receiving intervention
Secondary Outcome Measure Information:
Title
Pain intensity
Description
A numerical rating scale ranging from 0 (no pain) to 10 (worst pain imaginable) over the past 24 hours will be used to assess pain intensity.
Time Frame
Baseline, daily during treatment (5 days), and daily for 8 weeks after treatment
Title
Treatment expectancies
Description
The 6-item Healing Encounters and Attitudes Lists (HEAL) Short Form for Treatment Expectancy will be used to assess self-reported expectations about the study treatment. Participants are asked to rate their agreement with brief statements such as, "This treatment will be successful" and "I am confident in this treatment".
Time Frame
Baseline, and daily during treatment (5 days)
Title
Pain interference
Description
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.
Time Frame
Baseline, and weekly for 8 weeks after the end of treatment
Title
Physical function
Description
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.
Time Frame
Baseline, and weekly for 8 weeks after the end of treatment
Title
Depression (PROMIS)
Description
The 6-item PROMIS Depression Short Form assesses the severity of depressive symptoms experienced by an individual. Items are self-rated on a 5-point scale ranging from 1 ("Never") to 5 ("Always"). Raw score totals are converted to standardized T-scores, with a higher T-score representing greater depression symptom severity.
Time Frame
Baseline, and weekly for 8 weeks after the end of treatment
Title
Depression (PHQ-9)
Description
The 9-item PHQ-9 will be used as an additional indicator for changes in depression symptom severity, and to monitor for any risk of acute suicidality during the trial (item #9: "Thoughts that you would be better off dead, or of hurting yourself"). Items are self-rated on a 4-point scale ranging from 0 ("Not at all") to 3 ("Nearly every day"). Higher total scores indicate greater depression symptom severity.
Time Frame
Baseline, and weekly for 8 weeks after the end of treatment
Title
Anxiety
Description
The 6-item PROMIS Anxiety Short Form assesses the severity of anxiety symptoms experienced by an individual. Items are self-rated on a 5-point scale ranging from 1 ("Never") to 5 ("Always"). Raw score totals are converted to standardized T-scores, with a higher T-score representing greater anxiety symptom severity.
Time Frame
Baseline, and weekly for 8 weeks after the end of treatment
Title
Sleep disturbance
Description
The 6-item PROMIS Sleep Disturbance Short Form assesses the severity of sleep-related issues, such as trouble falling asleep, staying asleep, and experiencing non-restorative sleep. 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 sleep disturbance.
Time Frame
Baseline, and weekly for 8 weeks after the end of treatment
Title
Pain catastrophizing
Description
The 13-item Pain Catastrophizing Scale assesses the extent to which an individual engages in magnifying, rumination, and helplessness thoughts related to their pain experience. Items are self-rated on a 5-point scale ranging from 0 ("Not at all") to 4 ("All the time"). Higher total scores indicates higher levels of pain catastrophizing.
Time Frame
Baseline, and weekly for 8 weeks after the end of treatment
Title
Chronic pain acceptance
Description
The 8-item Chronic Pain Acceptance Questionnaire assesses one's level of acceptance and willingness to engage in valued activities despite the presence of chronic pain. Items are self-rated on a 7-point scale ranging from 0 ("Never true") to 6 ("Always true"). Higher total scores indicate greater levels of chronic pain acceptance.
Time Frame
Baseline, and weekly for 8 weeks after the end of treatment
Title
Patient global impression of change
Description
The Patient Global Impression of Change scale assesses the patient's perception of change in their overall health status resulting from a specific treatment. The single-item scale is self-rated on a 7-point scale ranging from 1 ("Very much improved") to 7 ("Very much worse").
Time Frame
Weekly for 8 weeks after the end of treatment
Title
Number of painful body regions
Description
The CHOIR Body Map is a visual tool that allows individuals to indicate the location(s) of their pain on a human body outline.
Time Frame
Baseline, and weekly for 8 weeks after the end of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Age 18 to 65 years Meets the International Association for the Study of Pain (IASP) diagnostic criteria for complex regional pain syndrome (CRPS) Primary complaint of CRPS-attributable pain for ≥3 months Average pain intensity of ≥3/10 over the last month Can read and comprehend English-language questionnaires Can receive text messages by phone Can identify a responsible adult who can provide transportation to and from infusion site for 5 consecutive days (Mon-Fri)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Theresa R Lii, MD, MS
Phone
650-724-2811
Email
tlii@stanford.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Theresa R Lii, MD, MS
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Ketamine and Midazolam Infusions for CRPS: Feasibility Study

We'll reach out to this number within 24 hrs