Efficacy of Intrathecal Oxytocin to Speed Recovery After Hip Surgery

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Efficacy of Intrathecal Oxytocin to Speed Recovery After Hip Surgery

Conditions
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Postoperative Pain

Intervention / Treatment
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* Drug: Oxytocin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Scheduled for unilateral, primary total hip replacement American Society of Anesthesiologists physical status 1-3 Exclusion Criteria: Pregnancy Currently Workman's Comp litigation related to hip replacement Taking greater than 100 milligrams of morphine (or equivalent) Suffering from a psychotic disorder or a recent psychiatric hospitalization

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxytocin<br>Oxytocin 100 micrograms administered intrathecally | Drug: Oxytocin<br>* spinal injection of oxytocin<br>* Other names: Pitocin;|
| Placebo Comparator: Placebos<br>Placebo injection administered intrathecally | Drug: Placebo<br>* spinal injection of placebo<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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. | 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 |