SLeep and OPioid UsE in Patients Undergoing Total Knee Arthroplasty

Study Overview
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Brief Summary
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Prescription opioid misuse and its associated negative effects have become an epidemic in the United States, and post-operative opioid use contributes to this terrible problem. Alternative strategies to opioid prescribing are thus highly sought after in the post-operative setting. Importantly, sleep and pain have a bi-directional relationship, and inadequate or impaired sleep regularly occur following orthopedic operations. Melatonin is an endogenous sleep hormone that can be administered exogenously, and that has been shown to have some potential as an analgesic agent. Here, using the premise that melatonin may improve sleep and pain in the post-operative setting, the investigators propose a randomized clinical trial in 120 participants undergoing total knee arthroplasties. Patients will be randomized to receive either sublingual melatonin 5 mg or matched placebo starting on post-operative day (POD) 0 and through POD . The investigators will measure post-operative opioid usage as the primary outcome, and post-operative pain scores as a secondary outcome. The primary safety outcome will be sedation level, as measured by the Richmond Agitation Sedation Scale (RASS). Sleep will be measured objectively using wrist-worn actigraphy. Participants will be followed through POD 28, and will also have baseline data on sleep, pain, and cognition obtained prior to surgery.

Official Title
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SLeep and OPioid UsE in Patients Undergoing Total Knee Arthroplasty

Conditions
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Opioid Use, Pain, Postoperative, Sleep, Delirium

Intervention / Treatment
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* Dietary Supplement: Melatonin
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults age 18 years and older Undergoing elective total knee arthroplasty (single knee) Exclusion Criteria: Non-English speakers Individuals with dementia Patients with liver cirrhosis Patients currently taking prescription sleep aids Patients with long-term (greater than 3 months prior to surgery), chronic opioid use

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Melatonin<br>Melatonin 5 mg sublingual nightly x 29 nights, starting on post-operative day 0. | Dietary Supplement: Melatonin<br>* Participants will take sublingual melatonin (or placebo) nightly for 29 doses after undergoing total knee replacement surgery.<br>|
| Placebo Comparator: Placebo<br>Placebo troche, sublingual nightly x 29 nights, starting on post-operative day 0. | Dietary Supplement: Placebo<br>* Participants will take sublingual melatonin (or placebo) nightly for 29 doses after undergoing total knee replacement surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid use | morphine milligram equivalents of opioid medications used by the participant | Post-operative day 0 through post-operative day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain level | Numerical pain scores reported by the patient following surgery using the Visual Analog Scale (Scale of 0-10, with 0 being no pain and 10 being the worst possible pain). | Post-operative day 0 through post-operative day 28 | 
| Other pain medicine usage | Usage of non-opioid analgesics used by the participant | Post-operative day 0 through post-operative day 28 | 
| Total daily sleep duration | Minutes of sleep obtained daily as measured by actigraphy | Post-operative day 0 through post-operative day 28 | 
| Nightly sleep duration | Minutes of sleep obtained nightly as measured by actigraphy | Post-operative day 0 through post-operative day 28 | 
| Sleep fragmentation | Mean/median length of the sleep bout during nightly sleep | Post-operative day 0 through post-operative day 28 |