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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Melatonin | Active Comparator | Melatonin 5 mg sublingual nightly x 29 nights, starting on post-operative day 0. |
|
| Placebo | Placebo Comparator | Placebo troche, sublingual nightly x 29 nights, starting on post-operative day 0. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Melatonin | Dietary Supplement | Participants will take sublingual melatonin (or placebo) nightly for 29 doses after undergoing total knee replacement surgery. |
|
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Delirium Incidence | Rates of inpatient delirium as measured by the Confusion Assessment Method | Post-operative day 0 through hospital discharge |
| Change in sleep duration pre and post-operatively | change in sleep duration (minutes) following surgery, using pre-operative sleep data as the comparator |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stuti Jaiswal, MD PhD | Scripps Clinic Medical Group | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Scripps Green Hospital | La Jolla | California | 92037-0001 | United States |
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| ID | Term |
|---|---|
| D010149 | Pain, Postoperative |
| D003693 | Delirium |
| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010146 | Pain |
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| ID | Term |
|---|---|
| D008550 | Melatonin |
| ID | Term |
|---|---|
| D014363 | Tryptamines |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Placebo | Dietary Supplement | Participants will take sublingual melatonin (or placebo) nightly for 29 doses after undergoing total knee replacement surgery. |
|
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 |
| Post-operative day 0 through post-operative day 28 |
| Sedation levels | Sedation levels, as measured by the Richmond Agitation Sedation Scale (RASS), during inpatient stay. RASS scores are measured on a scale of -5 to +5 with -5 equating to deeply sedated (deep coma) and +5 equating to extremely agitated/combative. | Post-operative day 0 through post-operative day 28 |
| Subjective sleep | subjective sleep scores as measured by the Richards Campbell Sleep Questionnaire while inpatient. The Richards Campbell Sleep Questionnaire is a 5-item questionnaire scored on a visual, 100 milimeter scale where the participants marks or selects where they fell on the scale in response to the specific question. Scores are assigned from 0-100 based on where the participant's response lies, with a higher score indicating better sleep. | Post-operative day 0 through post-operative day 28 |
| Delirium incidence in those with elevated obstructive sleep apnea risk | Delirium incidence in those with elevated OSA risk, based on the Berlin and STOP-BANG criteria | Post-operative day 0 through post-operative day 28 |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D003221 | Confusion |
| D019954 | Neurobehavioral Manifestations |
| D009422 | Nervous System Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D006571 | Heterocyclic Compounds |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |