Complex Regional Pain SyndromesPhase 2NCT05945147
Ketamine and Midazolam Infusions for CRPS: Feasibility Study
A Phase 2 study testing Ketamine, Midazolam and Normal Saline in people with Complex Regional Pain Syndromes, run by Stanford University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Complex Regional Pain Syndromes
- What is being tested?
- Ketamine, Midazolam and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2099to 31 May 2099
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Feasibility Study Comparing a Ketamine and Midazolam Infusion to a Midazolam-Only Infusion for Complex Regional Pain Syndrome
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).
Read the 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.
- Conditions
- Complex Regional Pain Syndromes
- Keywords
- Feasibility Study, Ketamine, Midazolam, Complex Regional Pain Syndrome, Active Placebo, Analgesics, Dissociative Anesthetics, Chronic Pain, Neuropathic Pain
- Medical subject headings
- Complex Regional Pain Syndromes, Chronic Pain, Neuralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Ketalar
An escalating dose of ketamine (0.15 to 0.4 mg/kg/hr) will be administered as 4-hour infusions over 5 consecutive days
MidazolamDrug
Also called Versed
A constant dose of midazolam (0.04 mg/kg/hr) will be administered as 4-hour infusions over 5 consecutive days
Normal SalineDrug
Also called 0.9% Sodium Chloride
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
| Study group | Role | What they receive |
|---|---|---|
| Ketamine and Midazolam | Experimental | Participants will receive intravenous infusions of ketamine and midazolam for 4 hours each day, over 5 consecutive days, in an outpatient setting. Receives: Drug: Ketamine; Drug: Midazolam |
| Midazolam and Saline | Placebo comparator | Participants will receive intravenous infusions of midazolam and normal saline for 4 hours each day, over 5 consecutive days, in an outpatient setting. Receives: Drug: Midazolam; Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 months after the study opens for enrollment
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.
Measured: 8 weeks after receiving intervention
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%.
Measured: Daily during intervention administration (5 days), and once at 8 weeks after receiving intervention
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%.
Measured: During intervention administration
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%.
Measured: 8 weeks after receiving intervention
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%.
Measured: During intervention administration
Number and types of adverse events
Adverse events will be elicited from the participant in a brief, open-ended structured interview.
Measured: 8 weeks after receiving intervention
Secondary outcomes (12)
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.
Measured: Baseline, daily during treatment (5 days), and daily for 8 weeks after treatment
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".
Measured: Baseline, and daily during treatment (5 days)
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.
Measured: Baseline, and weekly for 8 weeks after the end of 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.
Measured: Baseline, and weekly for 8 weeks after the end of treatment
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.
Measured: Baseline, and weekly for 8 weeks after the end of treatment
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.
Measured: Baseline, and weekly for 8 weeks after the end of treatment
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.
Measured: Baseline, and weekly for 8 weeks after the end of treatment
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.
Measured: Baseline, and weekly for 8 weeks after the end of treatment
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.
Measured: Baseline, and weekly for 8 weeks after the end of treatment
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.
Measured: Baseline, and weekly for 8 weeks after the end of treatment
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").
Measured: Weekly for 8 weeks after the end of 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.
Measured: Baseline, and weekly for 8 weeks after the end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2023
- Study start1 Jan 2099 (estimated)
- Primary completion30 Apr 2099 (estimated)
- Study completion31 May 2099 (estimated)
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Complex Regional Pain SyndromesStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Theresa Lii, Stanford University
- Investigators
- Theresa R Lii, MD, MS, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05945147
- Sponsor's protocol ID
- 66661
- Status last verified
- Nov 2024
- First submitted
- 26 Jun 2023
- Last updated
- 22 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility Study Comparing a Ketamine and Midazolam Infusion to a Midazolam-Only Infusion for Complex Regional Pain Syndrome
- ClinicalTrials.gov ID
- NCT05945147
- Acronym / sponsor ID
- 66661
- Conditions
- Complex Regional Pain Syndromes
- Keywords
- Feasibility Study, Ketamine, Midazolam, Complex Regional Pain Syndrome, Active Placebo, Analgesics, Dissociative Anesthetics, Chronic Pain
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 1 Jan 2099 (estimated)
- Primary completion
- 30 Apr 2099 (estimated)
- Study completion
- 31 May 2099 (estimated)
- First posted
- 14 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketamine and Midazolam | Experimental | Drug: Ketamine, Drug: MidazolamParticipants will receive intravenous infusions of ketamine and midazolam for 4 hours each day, over 5 consecutive days, in an outpatient setting. |
| Midazolam and Saline | Placebo comparator | Drug: Midazolam, Drug: Normal SalineParticipants will receive intravenous infusions of midazolam and normal saline for 4 hours each day, over 5 consecutive days, in an outpatient setting. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineAlso: KetalarAn escalating dose of ketamine (0.15 to 0.4 mg/kg/hr) will be administered as 4-hour infusions over 5 consecutive days | Drug | Ketamine and Midazolam |
| MidazolamAlso: VersedA constant dose of midazolam (0.04 mg/kg/hr) will be administered as 4-hour infusions over 5 consecutive days | Drug | Ketamine and Midazolam, Midazolam and Saline |
| Normal SalineAlso: 0.9% Sodium ChlorideAn escalating dose of normal saline (0.15 to 0.4 mg/kg/hr) will be administered as 4-hour infusions over 5 consecutive days | Drug | Midazolam and Saline |
Primary outcome
Number and proportion of patients who can undergo the steps of recruitment, informed consent, enrollment, and randomization
Time frame: 2 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 proportion of randomized participants who remain in the study until the last follow-up timepoint
Time frame: 8 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 masking
Time frame: Daily during intervention administration (5 days), and once at 8 weeks after receiving intervention
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
Time frame: During 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%.
Change in investigator masking
Time frame: 8 weeks after receiving intervention
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
Time frame: During 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 types of adverse events
Time frame: 8 weeks after receiving intervention
Adverse events will be elicited from the participant in a brief, open-ended structured interview.
12 secondary outcomes
Pain intensity
Time frame: Baseline, daily during treatment (5 days), and daily for 8 weeks after treatment
Treatment expectancies
Time frame: Baseline, and daily during treatment (5 days)
Pain interference
Time frame: Baseline, and weekly for 8 weeks after the end of treatment
Physical function
Time frame: Baseline, and weekly for 8 weeks after the end of treatment
Depression (PROMIS)
Time frame: Baseline, and weekly for 8 weeks after the end of treatment
Depression (PHQ-9)
Time frame: Baseline, and weekly for 8 weeks after the end of treatment
Anxiety
Time frame: Baseline, and weekly for 8 weeks after the end of treatment
Sleep disturbance
Time frame: Baseline, and weekly for 8 weeks after the end of treatment
Pain catastrophizing
Time frame: Baseline, and weekly for 8 weeks after the end of treatment
Chronic pain acceptance
Time frame: Baseline, and weekly for 8 weeks after the end of treatment
Patient global impression of change
Time frame: Weekly for 8 weeks after the end of treatment
Number of painful body regions
Time frame: Baseline, and weekly for 8 weeks after the end of treatment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2024.
- Individual participant dataSharing planned: No
Related trials for Complex Regional Pain Syndromes
RecruitingPhase 3
Evaluation of IV AMBTX-01 (Neridronate) for Treatment of CRPS Type 1 (CRPS-RISE)
Complex Regional Pain Syndrome Type I
Recruiting
The Effectiveness of Conservative Treatment in Patients With Complex Regional Pain Syndrome.
CRPS (Complex Regional Pain Syndromes)
RecruitingPhase 3
Phase 3, Open-Label Extension Study of AMBTX-01 (Neridronate) for Complex Regional Pain Syndrome Type 1
Complex Regional Pain Syndrome Type I
Active, not recruiting
Transcranial Magnetic Stimulation for Chronic Neuropathic Pain
Chronic Neuropathic Pain, Post-Stroke Pain
Recruiting
Clinical and Cerebral Changes Following Multifaceted Rehabilitation of Complex Regional Pain Syndrome
Complex Regional Pain Syndrome (CRPS)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Theresa R Lii, MD, MS principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ketamine, Midazolam and Normal Saline in people with Complex Regional Pain Syndromes, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 22 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number and proportion of patients who can undergo the steps of recruitment, informed consent, enrollment, and randomization (time frame: 2 months after the study opens for enrollment). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2024.