MedPath

Ketamine and Midazolam Infusions for CRPS: Feasibility Study

Phase 2
Withdrawn
Conditions
Complex Regional Pain Syndromes
Interventions
Registration Number
NCT05945147
Lead Sponsor
Stanford University
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:

1. Assess whether the recruitment and retention rate observed in this feasibility study can support a larger clinical trial.

2. Evaluate whether participants can adhere to study procedures.

3. 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.

4. Gather preliminary data on clinically-relevant outcomes for CRPS.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Midazolam and SalineNormal SalineParticipants will receive intravenous infusions of midazolam and normal saline for 4 hours each day, over 5 consecutive days, in an outpatient setting.
Ketamine and MidazolamKetamineParticipants will receive intravenous infusions of ketamine and midazolam for 4 hours each day, over 5 consecutive days, in an outpatient setting.
Ketamine and MidazolamMidazolamParticipants will receive intravenous infusions of ketamine and midazolam for 4 hours each day, over 5 consecutive days, in an outpatient setting.
Midazolam and SalineMidazolamParticipants will receive intravenous infusions of midazolam and normal saline for 4 hours each day, over 5 consecutive days, in an outpatient setting.
Primary Outcome Measures
NameTimeMethod
Change in investigator maskingDuring intervention administration

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 proportion of patients who can undergo the steps of recruitment, informed consent, enrollment, and randomization2 months after the study opens for enrollment

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 types of adverse events8 weeks after receiving intervention

Adverse events will be elicited from the participant in a brief, open-ended structured interview.

Number and proportion of randomized participants who remain in the study until the last follow-up timepoint8 weeks after receiving intervention

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 maskingDuring intervention administration

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%.

Secondary Outcome Measures
NameTimeMethod
Pain interferenceBaseline, and weekly for 8 weeks after the end of treatment

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.

AnxietyBaseline, and weekly for 8 weeks after the end of treatment

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 disturbanceBaseline, and weekly for 8 weeks after the end of treatment

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 catastrophizingBaseline, and weekly for 8 weeks after the end of treatment

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.

Pain intensityBaseline, daily during treatment (5 days), and daily for 8 weeks after treatment

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.

Number of painful body regionsBaseline, and weekly for 8 weeks after the end of treatment

The CHOIR Body Map is a visual tool that allows individuals to indicate the location(s) of their pain on a human body outline.

Treatment expectanciesBaseline, and daily during treatment (5 days)

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".

Physical functionBaseline, and weekly for 8 weeks after the end of treatment

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 (PHQ-9)Baseline, and weekly for 8 weeks after the end of treatment

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.

Depression (PROMIS)Baseline, and weekly for 8 weeks after the end of treatment

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.

Chronic pain acceptanceBaseline, and weekly for 8 weeks after the end of treatment

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 changeWeekly for 8 weeks after the end of treatment

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").

Trial Locations

Locations (1)

Stanford University

🇺🇸

Stanford, California, United States

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