Sleep Quality Post-TKAPhase 4NCT07598734
Doxepin Alone or Combined With Ramelteon Versus Placebo for Improving Sleep Quality After Primary Total Knee Arthroplasty
A Phase 4 study testing Doxepin 6 mg and Ramelteon 8 mg in people with Sleep Quality Post-TKA and Postoperative Knee Function, run by University of Washington at 1 site in United States.
Trial summary
Many patients experience poor sleep during recovery after total knee arthroplasty (TKA). Disturbed sleep can last weeks to months and may worsen pain, slow healing, and reduce overall quality of life. Few safe, effective, evidence-based options exist to improve sleep during this recovery period. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Sleep Quality Post-TKA, Postoperative Knee Function, Quality of Life After Primary TKA
- What is being tested?
- Doxepin 6 mg and Ramelteon 8 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 129 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2026to Jun 2028
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Those receiving primary total knee arthroplasty (TKA)
- 80 years or less, age 18 or greater
Who cannot join
- History of cardiovascular bundle branch block
- Actively taking selecrtive serotoin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), or having treatment via counseling/psychotherapy for major depression or anxiety, bipolar, or psychotic disorder
- Pre-operative narcotics (defined as more than 1 prescription in the past 3 months)
- Self-reported use of alcohol in excess of >2 drinks/day (in men) and > 1 drink/day (in women)
- Use of prescription sleep aids (e.g., Ambien, Trazadone) prior to surgery (i.e., melatonin or other OTC sleep aids are permitted)
- History of major sleep disorder (e.g., obstructive sleep apnea (OSA), restless leg syndrome, narcolepsy)
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- Pregnant, breastfeeding or planning to become pregnant in the next 3 months post-surgery. No pregnancy testing will be performed; screening will rely solely on participant self-report.
- Unable to take the study medication(s) due to contraindications with other medications the patient uses
- Have been diagnosed with (or are at risk of) narrow-angle or angle-closure glaucoma. In order to be eligible, participants must be able to report that they have had their eyes dilated within the past year without problems.
- Have severe urinary retention or difficulty emptying your bladder.
- Had glaucoma-related eye procedures (e.g., laser iridotomy)
- Ongoing use of glaucoma eye drops.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
University of Washington Medical Center Hip & Knee Center
Seattle, Washington, 98133
Portia Morgan, 206-668-3674, morganp9@uw.edu
Nicholas M Hernandez, MD
About this study
Official title: Doxepin Versus Doxepin and Ramelteon Versus Placebo to Improve Sleep Quality After Primary Total Knee Arthroplasty: A Randomized Controlled Trial
Many patients experience poor sleep during recovery after total knee arthroplasty (TKA). Disturbed sleep can last weeks to months and may worsen pain, slow healing, and reduce overall quality of life. Few safe, effective, evidence-based options exist to improve sleep during this recovery period. This study aims to determine whether the medications doxepin, either alone or in combination with ramelteon, can improve sleep quality during early recovery after TKA. The investigators will also evaluate whether improved sleep leads to better pain control, knee function, and overall quality of life.
Read the detailed description
This randomized, placebo-controlled clinical trial seeks to answer the following question: Is doxepin or combination therapy consisting of doxepin plus ramelteon superior to placebo in terms of (1) sleep quality as measured by the Insomnia Severity Index, (2) postoperative knee function as measured by KOOS-JR, KOOS-PS, or (3) overall health-related quality of life during the first three months after total knee arthroplasty.
- Being tested
- Doxepin 6 mg, Ramelteon 8 mg, Placebo Tablets
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Doxepin 6 mgDrug
Doxepin 6 mg administered orally once nightly for sleep during the first 6 weeks of the postoperative period following total knee arthroplasty
Ramelteon 8 mgDrug
Ramelteon 8 mg administered orally once nightly for sleep during the first 6 weeks of the postoperative period following total knee arthroplasty
Placebo TabletsDrug
Placebo administered orally once nightly for sleep during the first 6 weeks of the postoperative period following total knee arthroplasty
| Study group | Role | What they receive |
|---|---|---|
| Doxepin 6 mg | Experimental | Participants receive doxepin 6 mg and matching placebo orally once nightly for sleep during the first 6 weeks postoperative period following total knee arthroplasty. Receives: Drug: Doxepin 6 mg |
| Doxepin 6 mg and Ramelteon 8mg | Experimental | Participants receive doxepin 6 mg and ramelteon 8 mg orally once nightly for sleep during the first 6 weeks postoperative period following total knee arthroplasty. Receives: Drug: Doxepin 6 mg; Drug: Ramelteon 8 mg |
| Placebo | Placebo comparator | Participants receive 2 matching placebos orally once nightly for sleep during the first 6 weeks postoperative period following total knee arthroplasty. Receives: Drug: Placebo Tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insomnia Severity Index (ISI) scores (sleep quality)
Insomnia Severity Index (ISI) The Insomnia Severity Index is a 7-item self-reported questionnaire assessing the nature, severity, and impact of insomnia.
- Score range: 0 to 28
- Interpretation: Higher scores indicate worse insomnia severity
Score categories:
- 0-7: No clinically significant insomnia
- 8-14: Subthreshold insomnia
- 15-21: Clinical insomnia (moderate severity)
- 22-28: Clinical insomnia (severe)
Measured: Baseline; 2 weeks postoperatively; 6 weeks postoperatively; 3 months postoperatively
Secondary outcomes (3)
Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS)
Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS):
The KOOS-PS is a 7-item patient-reported outcome measure assessing knee-related physical function, including activities such as rising from bed, putting on socks, rising from sitting, bending to the floor, twisting/pivoting, kneeling, and squatting . Each item is scored on a 5-point Likert scale (None to Extreme). Scores are transformed to a normalized scale ranging from 0 to 100, with higher scores indicating worse physical function (greater disability).
Measured: Baseline; 2 weeks postoperatively; 6 weeks postoperatively; 3 months postoperatively.
Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR)
Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR):
The KOOS-JR is a patient-reported outcome measure assessing knee pain, stiffness, and functional limitations during activities of daily living over the past week, including tasks such as twisting/pivoting, stair navigation, standing, rising from sitting, and bending . The instrument consists of 7 items scored on a 5-point Likert scale (None to Extreme). Raw scores (range 0-28) are summed and converted to an interval score ranging from 0 to 100, where 0 represents total knee disability and 100 represents perfect knee health (higher scores indicate better outcomes)
Measured: Baseline; 2 weeks postoperatively; 6 weeks postoperatively; 3 months postoperatively
Patient-Reported Outcomes Measurement Information System Global-10 (PROMIS-10)
Patient-Reported Outcomes Measurement Information System Global-10 (PROMIS-10):
The PROMIS-10 is a 10-item patient-reported outcome measure assessing global physical health, mental health, pain, fatigue, and social functioning. Items are scored on 5-point Likert scales (e.g., Excellent to Poor; Not at all to Very much), with one pain item scored from 0 to 10. Raw scores are summed and converted to standardized T-scores for Global Physical Health and Global Mental Health, each ranging approximately from 0 to 100 (mean 50, standard deviation 10), where higher scores indicate better health status
Measured: Baseline; 2 weeks postoperatively; 6 weeks postoperatively; 3 months postoperatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2026
- Study startJun 2026 (estimated)
- Primary completionJun 2028 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sleep Quality Post-TKAStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a randomized, double blind (surgeon and patient), placebo-controlled, parallel-group clinical trial comparing two medications against a placebo, enrolling sequential patients undergoing primary total knee arthroplasty, with outcomes assessed over a 3-month postoperative period to evaluate sleep quality.
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 129 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nick Hernandez, University of Washington
- Investigators
- Nicholas M Hernandez, MD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07598734
- Sponsor's protocol ID
- STUDY00024373
- Status last verified
- May 2026
- First submitted
- 1 May 2026
- Last updated
- 20 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No