SLeep and OPioid UsE in Patients Undergoing Total Knee Arthroplasty (SLOPE)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pain, Postoperative; Delirium; Sleep; Opioid Use
• Intervention / Treatment: Dietary supplement: Melatonin; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037-0001
      • Scripps Green Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Scripps Health
• Investigators: Principal Investigator: Stuti Jaiswal, MD PhD, Scripps Clinic Medical Group

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: January 27, 2020
• First Submitted That Met QC Criteria: January 27, 2020
• First Posted (Actual): January 30, 2020

Study Record Updates

• Last Update Posted (Actual): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: 65106563709047

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No