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Cessation of funding period prior to completion, due to slow recruitment during the pandemic.
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The purpose of this study is to determine the effect of intrathecal oxytocin on speed of reduction in pain for the first 60 days after hip surgery.
This is a single-center, NIH funded clinical study at Wake Forest Baptist Medical Center. The investigators anticipate that intrathecal oxytocin will speed recovery from pain after major surgery (hip arthroplasty). For this study, the investigators will use a randomized, controlled and blinded study of intrathecal oxytocin in patients scheduled for hip arthroplasty, with primary outcome being the slope of change in pain over the first 60 days following surgery, using growth curve modeling and a ln(time) function.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Oxytocin | Experimental | Oxytocin 100 micrograms administered intrathecally |
|
| Placebos | Placebo Comparator | Placebo injection administered intrathecally |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oxytocin | Drug | spinal injection of oxytocin |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Comparison of Adjusted Trajectory Model for Pain Between Oxytocin and Placebo--Intercept | Daily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. The daily pain intensity was the WORST pain (not the average pain) in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain. Values represent an intercept of modeled worst daily pain on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model. | The first day after hospital discharge |
| Comparison of Adjusted Trajectory Model for Pain Between Oxytocin and Placebo--Slope | Daily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. The daily pain intensity was the WORST pain in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain. Slope is defined as change in pain . Values represent the slope of modeled worst daily pain (0-10 scale as described above) divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model. | Postoperative Day 1 through Postoperative Day 60 |
| Measure | Description | Time Frame |
|---|---|---|
| Comparison of Adjusted Trajectory Model for Daily Steps Between Oxytocin and Placebo--Intercept | Daily steps for each subject were fitted using growth curve model with parameters of intercept (modeled initial steps) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. This is considered as the modeled change in activity listed in the protocol. Values represent an intercept of modeled daily steps on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| James C Eisenach, MD | Wake Forest University Health Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wake Forest Baptist Medical Center | Winston-Salem | North Carolina | 27157 | United States |
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Enrollment occurred greater or equal to 2 weeks prior to surgery. A total of 28 individuals were excluded prior to assignment to groups during the period prior to surgery because of withdrawal of consent (n=25) or cancellation of the planned surgery (n=3).
Enrollment occurred from January 12, 2017 to August 3, 2020 at the Orthopeadic Clinics of Atrium Wake Forest Baptist and Davie County facilities.
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| ID | Title | Description |
|---|---|---|
| FG000 | Oxytocin | Oxytocin 100 micrograms administered intrathecally Oxytocin: spinal injection of oxytocin |
| FG001 | Placebo | Placebo injection administered intrathecally Placebos: spinal injection of placebo |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | Oxytocin | Oxytocin 100 micrograms administered intrathecally Oxytocin: spinal injection of oxytocin |
| BG001 | Placebo | Placebo injection administered intrathecally Placebos: spinal injection of placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Comparison of Adjusted Trajectory Model for Pain Between Oxytocin and Placebo--Intercept | Daily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. The daily pain intensity was the WORST pain (not the average pain) in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain. Values represent an intercept of modeled worst daily pain on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model. | Posted | Number | 95% Confidence Interval | score on a scale | The first day after hospital discharge |
|
Deaths and Serious adverse events were evaluated from baseline through month 6. Non-serious adverse events were evaluated from baseline through month 2.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Oxytocin | Oxytocin 100 micrograms administered intrathecally Oxytocin: spinal injection of oxytocin |
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The trial was terminated early because of depletion of funding. Power analysis was based on 120 subjects and only 90 were studied before termination of funding .
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. James Eisenach | Wake Forest University School of Medicine | 336-716-4182 | eisenach@wakehealth.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 13, 2016 | Jan 5, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 3, 2022 | Jan 5, 2022 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Sep 30, 2020 | Dec 17, 2021 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D010149 | Pain, Postoperative |
| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010146 | Pain |
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| ID | Term |
|---|---|
| D010121 | Oxytocin |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D010909 | Pituitary Hormones, Posterior |
| D010907 | Pituitary Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
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| Placebo | Drug | spinal injection of placebo |
|
|
| The first day after hospital discharge |
| Comparison of Adjusted Trajectory Model for Daily Steps Between Oxytocin and Placebo--Slope | Daily steps for each subject were fitted using growth curve model with parameters of intercept (modeled initial steps) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. This is considered as the modeled change in activity listed in the protocol. Values represent the slope of daily steps divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model. | Postoperative Day 1 through Postoperative Day 60 |
| Comparison of Adjusted Trajectory Model for World Health Organization Disability Assessment Score 2.0 Value Between Oxytocin and Placebo--Intercept | Weekly World Health Organization Disability Assessment Score 2.0 (WHODAS 2.0) value for each subject was fitted using growth curve model with parameters of intercept (modeled initial score) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. Scale is 12 to 36 with higher scores meaning greater disability. Values represent an intercept of modeled WHODAS 2.0 score one week after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model. | Modeled WHODAS 2.0 one week after hospital discharge |
| Comparison of Adjusted Trajectory Model for World Health Organization Disability Assessment Score 2.0 Value Between Oxytocin and Placebo--Slope | Weekly World Health Organization Disability Assessment Score 2.0 (WHODAS 2.0) value for each subject was fitted using growth curve model with parameters of intercept (modeled initial score) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. Scale is 12 to 36 with higher scores meaning greater disability. Values represent the slope of WHODAS 2.0 score divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model. | Postoperative Day 7 through Postoperative Day 56 |
| Comparison of Adjusted Trajectory Model for Probability of Taking Opioids Daily Between Oxytocin and Placebo--Intercept | Daily probability of taking opioids for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. Values represent an intercept of modeled probability of taking opioid, on a 0-1 probability scale, on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with standard deviation based on the model. | The first day after hospital discharge |
| Comparison of Adjusted Trajectory Model for Probability of Taking Opioids Daily Between Oxytocin and Placebo--Slope | Daily probability of taking opioids for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. Values represent the slope of daily probability of taking opioids divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model | Postoperative Day 1 through Postoperative Day 60 |
| Iowa Gambling Task | This is a computer based card game which assesses risk taking and impulsivity in which a score of -100 to 100 is calculated. Lower numbers indicate greater impulsiivity | Preoperative, 2 months after surgery |
| Wisconsin Card Sort Task | This is a physical card sorting game which measures attention to shifts in implicit rules as the game progresses. Perseverative errors are the number of sequential errors when rules of the game shift and reflect dysfunction of attention. This score ranges from 0 to 64 with larger numbers reflecting more dysfunction of attention. | Preoperative, 2 months after surgery |
| Tampa Scale of Kinesiophobia | This 17-question scale assesses the degree of fear of pain from joint movement and is commonly used in orthopedic injury or surgery studies. The scale ranges from 17 to 68 with 17 indicating no fear of movement and 68 indicating severe fear. | Preoperative, 2 months after surgery |
| Did not receive study drug: unable to obtain study drug from formulating pharmacy |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Worst daily pain | From daily diaries completed for 2 weeks prior to surgery in which the participant rated each day the worst pain in the past 24 hours with 0=no pain and 10=worst pain imaginable | Mean | Standard Deviation | units on a scale |
|
| Daily steps | Steps each day for 2 weeks prior to surgery as measured with an activity monitor | Mean | Standard Deviation | Steps per day |
|
| Disability | Preoperative measure of disability on the World Health Organization Disability Assessment Scale 2.0 where no disability = 12 and severe disability =36 | Mean | Standard Deviation | units on a scale |
|
| OG001 | Placebo | Placebo injection administered intrathecally Placebos: spinal injection of placebo |
|
|
|
| Primary | Comparison of Adjusted Trajectory Model for Pain Between Oxytocin and Placebo--Slope | Daily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. The daily pain intensity was the WORST pain in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain. Slope is defined as change in pain . Values represent the slope of modeled worst daily pain (0-10 scale as described above) divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model. | Posted | Number | 95% Confidence Interval | Score on a scale | Postoperative Day 1 through Postoperative Day 60 |
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|
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| Secondary | Comparison of Adjusted Trajectory Model for Daily Steps Between Oxytocin and Placebo--Intercept | Daily steps for each subject were fitted using growth curve model with parameters of intercept (modeled initial steps) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. This is considered as the modeled change in activity listed in the protocol. Values represent an intercept of modeled daily steps on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model. | Posted | Number | 95% Confidence Interval | Daily Steps | The first day after hospital discharge |
|
|
|
|
| Secondary | Comparison of Adjusted Trajectory Model for Daily Steps Between Oxytocin and Placebo--Slope | Daily steps for each subject were fitted using growth curve model with parameters of intercept (modeled initial steps) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. This is considered as the modeled change in activity listed in the protocol. Values represent the slope of daily steps divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model. | Posted | Number | 95% Confidence Interval | Daily steps | Postoperative Day 1 through Postoperative Day 60 |
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|
|
| Secondary | Comparison of Adjusted Trajectory Model for World Health Organization Disability Assessment Score 2.0 Value Between Oxytocin and Placebo--Intercept | Weekly World Health Organization Disability Assessment Score 2.0 (WHODAS 2.0) value for each subject was fitted using growth curve model with parameters of intercept (modeled initial score) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. Scale is 12 to 36 with higher scores meaning greater disability. Values represent an intercept of modeled WHODAS 2.0 score one week after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model. | The estimates were conducted using a linear mixed effects model contrasting differences in the oxytocin group versus placebo. In all cases, these differences are adjusted for prognostic variables including baseline World Health Organization Disability Assessment Score 2.0 value, baseline opioid use, age, sex, baseline PROMIS depression and number of other painful conditions. | Posted | Number | 95% Confidence Interval | score on a scale | Modeled WHODAS 2.0 one week after hospital discharge |
|
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|
|
| Secondary | Comparison of Adjusted Trajectory Model for World Health Organization Disability Assessment Score 2.0 Value Between Oxytocin and Placebo--Slope | Weekly World Health Organization Disability Assessment Score 2.0 (WHODAS 2.0) value for each subject was fitted using growth curve model with parameters of intercept (modeled initial score) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. Scale is 12 to 36 with higher scores meaning greater disability. Values represent the slope of WHODAS 2.0 score divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model. | The estimates were conducted using a linear mixed effects model contrasting differences in the oxytocin group versus placebo. In all cases, these differences are adjusted for prognostic variables including baseline World Health Organization Disability Assessment Score 2.0 value, baseline opioid use, age, sex, baseline PROMIS depression and number of other painful conditions. | Posted | Number | 95% Confidence Interval | Score on a scale/ln(days) | Postoperative Day 7 through Postoperative Day 56 |
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| Secondary | Comparison of Adjusted Trajectory Model for Probability of Taking Opioids Daily Between Oxytocin and Placebo--Intercept | Daily probability of taking opioids for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. Values represent an intercept of modeled probability of taking opioid, on a 0-1 probability scale, on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with standard deviation based on the model. | Posted | Number | 95% Confidence Interval | Probability of taking opioids | The first day after hospital discharge |
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| Secondary | Comparison of Adjusted Trajectory Model for Probability of Taking Opioids Daily Between Oxytocin and Placebo--Slope | Daily probability of taking opioids for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. Values represent the slope of daily probability of taking opioids divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model | Posted | Number | 95% Confidence Interval | Probability of taking opioids/ln(days) | Postoperative Day 1 through Postoperative Day 60 |
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|
| Secondary | Iowa Gambling Task | This is a computer based card game which assesses risk taking and impulsivity in which a score of -100 to 100 is calculated. Lower numbers indicate greater impulsiivity | Posted | Mean | Standard Deviation | units on a scale | Preoperative, 2 months after surgery |
|
|
|
|
| Secondary | Wisconsin Card Sort Task | This is a physical card sorting game which measures attention to shifts in implicit rules as the game progresses. Perseverative errors are the number of sequential errors when rules of the game shift and reflect dysfunction of attention. This score ranges from 0 to 64 with larger numbers reflecting more dysfunction of attention. | Posted | Mean | Standard Deviation | units on a scale | Preoperative, 2 months after surgery |
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| Secondary | Tampa Scale of Kinesiophobia | This 17-question scale assesses the degree of fear of pain from joint movement and is commonly used in orthopedic injury or surgery studies. The scale ranges from 17 to 68 with 17 indicating no fear of movement and 68 indicating severe fear. | Posted | Mean | Standard Deviation | units on a scale | Preoperative, 2 months after surgery |
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|
|
| 0 |
| 44 |
| 0 |
| 44 |
| 0 |
| 44 |
| EG001 | Placebo | Placebo injection administered intrathecally Placebos: spinal injection of placebo | 0 | 46 | 0 | 46 | 0 | 46 |
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| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
A likelihood-ratio test for change in pain was conducted for each outcome comparing a model with and without oxytocin treatment group. A statistically significant result is interpreted as evidence to support that the oxytocin treatment impacts some element of change after surgery (i.e, intercept or slope).
A likelihood-ratio test for change in pain was conducted for each outcome comparing a model with and without oxytocin treatment group. A statistically significant result is interpreted as evidence to support that the oxytocin treatment impacts some element of change after surgery (i.e, intercept or slope).
A likelihood-ratio test for change in pain was conducted for each outcome comparing a model with and without oxytocin treatment group. A statistically significant result is interpreted as evidence to support that the oxytocin treatment impacts some element of change after surgery (i.e, intercept or slope). |
A likelihood-ratio test for change in World Health Organization Disability Assessment Score 2.0 value was conducted for each outcome comparing a model with and without oxytocin treatment group. A statistically significant result is interpreted as evidence to support that the oxytocin treatment impacts some element of change after surgery (i.e, intercept or slope). |
A likelihood-ratio test for change in pain was conducted for each outcome comparing a model with and without oxytocin treatment group. A statistically significant result is interpreted as evidence to support that the oxytocin treatment impacts some element of change after surgery (i.e, intercept or slope).
A likelihood-ratio test for change in pain was conducted for each outcome comparing a model with and without oxytocin treatment group. A statistically significant result is interpreted as evidence to support that the oxytocin treatment impacts some element of change after surgery (i.e, intercept or slope).
A likelihood-ratio test for change in pain was conducted for each outcome comparing a model with and without oxytocin treatment group. A statistically significant result is interpreted as evidence to support that the oxytocin treatment impacts some element of change after surgery (i.e, intercept or slope).