Chronic Pain, Depression
Conditions
Keywords
Chronic Pain, Depression, Ketamine, Propofol, Sedation, Psychotropic Drugs, Hypnotics and Sedatives, Dissociative Anesthetics
Brief summary
The goal of this clinical trial is to compare ketamine to a placebo when given as a single infusion during IV sedation in adults with chronic pain and depression. We do not know whether ketamine will be more effective than placebo under these circumstances. This study aims to: * Evaluate whether placebo is non-inferior to ketamine in treating chronic pain and depression, when delivered under propofol sedation * 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
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 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 and recall 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. A n=6 pilot feasibility phase will precede the fully-powered n=34 randomized controlled trial. Enrollment for the n=6 pilot phase is complete as of 6/19/2025.
Interventions
DRUGKetamine
0.5 mg/kg ketamine infused intravenously over 40 minutes
DRUGNormal saline
0.9% normal saline infused intravenously over 40 minutes
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 70 years old * Comfortable speaking and writing in English * Chronic pain present daily 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain intensity in the past 24 hours | screening; 1, 7, 14, 21 and 28 days after treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Depression Severity and Blinding | screening; day of infusion pre-treatment; 7, 14, 21 and 28 days after treatment | The 16-item Quick Inventory of Depressive Symptomatology Self-Report will be used to assess the severity of depressive symptoms. Items are self-rated on a 4-point scale tailored to each depression-related symptom. Higher total scores indicate greater depression symptom severity. Blinding will be assessed by asking participants to guess which treatment they received and rate their certainty on a simple 0-100 scale. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants who accurately recall intra-sedation events | day of infusion post-treatment | 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. |
| Participant expectations | screening; day of infusion post-treatment; 1, 7, 14, 21 and 28 days after treatment | Expectations will be measured by asking participants to rate how effective they expect their treatment will be using a visual analog sliding scale from 0 (Not effective at all) to 100 (Completely effective). They will then be asked to rate their level of confidence on a scale from 0 to 100%. |
| Pressure pain threshold | day of infusion pre-treatment; day of infusion post-treatment | 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. |
| Mechanical temporal summation | day of infusion pre-treatment; day of infusion post-treatment | Mechanical temporal summation will be measured by applying the blunt tip of a thin flexible filament to the back of the hand and the lumbar region. Participants will be asked report pain intensity on a sale from 0 to 100 after a single application and after 10 repeated applications. |
| Conditioned pain modulation | day of infusion pre-treatment; day of infusion post-treatment | Conditioned pain modulation (CPM) measures the ability of the nervous system to inhibit a painful stimulus in the presence of another aversive stimulus. In this study, participants will immerse one hand in cold water and undergo pressure pain threshold measurements in the opposite trapezius muscle before, during, and after immersion. |
| Number of painful body regions | screening; day of infusion pre-treatment; day of infusion post-treatment; 1, 7, 14, 21 and 28 days after 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. |
| Pain interference | screening; day of infusion pre-treatment; 7, 14, 21 and 28 days after treatment | The 8-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. |
| Change in pain medication utilization | 1, 7, 14, 21 and 28 days after treatment | Participants are asked to rate how their pain medication usage has changed compared to before treatment |
| Number and severity of adverse events related to sedation | during treatment; day of infusion post-treatment; 1, 7, 14, 21 and 28 days after treatment | 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). |
| Sleep disturbance | screening; day of infusion pre-treatment; 7, 14, 21 and 28 days after treatment | The 8-item PROMIS Sleep Disturbance Short Form assesses an individual's perception of their sleep quality. Items are self-rated on a 5-point scale ranging from 1 (Not at all) to 5 (Very much). Raw scores are converted to standardized T-scores, with higher a T-score representing more severe sleep disturbance. |
| Anxiety symptom severity | screening; day of infusion pre-treatment; 14 and 28 days after treatment] | The 7-item Generalized Anxiety Disorder (GAD-7) Scale assesses the severity of anxiety symptomsover the past two weeks. Items are self-rated on a 4-point scale ranging from 0 (Not at all) to 3 (Nearly every day), reflecting the frequency of symptoms. Higher total scores indicate greater anxiety symptom severity. |
| Peace of mind | screening; day of infusion pre-treatment; 7 and 28 days after treatment | The 7-item Peace of Mind Scale assesses an individual's overall sense of inner calm and contentment. Items are self-rated on a 5-point scale ranging from 1 (Not at all) to 5 (All of the time). Higher total scores reflect a greater sense of peace of mind. |
| Emotion regulation | screening; day of infusion pre-treatment; 7 and 28 days after treatment | The 10-item Emotion Regulation Questionnaire assesses individual differences in the habitual use of cognitive reappraisal and expressive suppression strategies. Items are self-rated on a 7-point scale ranging from 1 (Strongly disagree) to 7 (Strongly agree). Higher scores on the cognitive reappraisal subscale indicate a greater tendency to reinterpret situations to manage emotions, while higher scores on the expressive suppression subscale indicate a greater tendency to inhibit outward emotional expression. |
| Anhedonia | screening; day of infusion pre-treatment; 14 and 28 days after treatment | The 14-item Snaith-Hamilton Pleasure Scale measures an individual's capacity to experience pleasure from various activities over the past 2 weeks, the absence of which indicates anhedonia. Items are self-rated on a 4-point scale ranging from 0 (Strongly disagree) to 3 (Strongly agree). Lower total scores indicate greater degree of anhedonia. |
| Enrollment rate | from date of opening enrollment to the date of consent from the last participant, assessed up to 60 months | 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. |
| Consent fraction | from date of opening enrollment to the date of consent from the last participant, assessed up to 60 months | The proportion of patients who are contacted by study staff for recruitment who provide written informed consent to study procedures. |
| Participant Experience Survey | through study completion, an average of 4 weeks | Participants are asked at the end of the study to rate their experience with study procedures and to provide feedback for improvement. |
| Physical function | screening; day of infusion pre-treatment; 7, 14, 21 and 28 days after treatment | The 20-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. |
| Side effects related to ketamine | day of infusion post-treatment; 1, 7, 14, 21 and 28 days after treatment | The Ketamine Side Effect Tool (KSET) is a standardized questionnaire designed to systematically assess the side effects experienced during or after ketamine administration. It covers a range of potential adverse effects, including dissociative, cardiovascular, and psychotomimetic symptoms. Participants are asked to rate the severity of each adverse effect as 'Never', 'Mild', 'Moderate', or 'Severe'. |
Countries
United States
Outcome results
None listed