Promoting Sleep to Alleviate Pain - Arthroplasty (PROSAP-A)

Preoperative Sleep-promotion to Achieve Improved Postoperative Pain Control and Recovery: a Randomized, Controlled Trial

PROSAP-A is a perioperative randomized, controlled trial with a 12-month follow-up period after total knee arthroplasty (TKA) or total hip arthroplasty (THA), aiming to investigate both acute and long-term postoperative effects of preoperative sleep-promotion. Participants with clinically significant insomnia symptoms will be randomized to a brief, hybrid version of cognitive behavioral therapy for insomnia (CBT-I) or sleep education therapy, administered over a 4-week period, prior to surgery. The primary objective is to evaluate effects of preoperative sleep-promotion on acute postoperative pain control. Secondary objectives include evaluation of postoperative sleep, recovery, mental health, cognitive function and alterations in blood biomarkers.

Study Overview

• Status: Recruiting
• Conditions: Pain, Postoperative; Postoperative Complications; Osteoarthritis, Knee; Insomnia; Surgery; Osteoarthritis, Hip
• Intervention / Treatment: Behavioral: Cognitive behavioral therapy for insomnia (CBT-I); Behavioral: Sleep education therapy (SET)

Detailed Description

Although preoperative sleep disturbance is associated with poorer acute postoperative pain control, as well as development of chronic postsurgical pain, only very limited attempts have been made to target preoperative sleep to achieve improved postoperative outcomes. This study addresses two chronic pain populations, TKA and THA patients, that suffer severely due to both sleep disturbance and painful symptoms. Patients who meet eligibility criteria, including insomnia severity index score >10 and confirmed DSM-V criteria for persistent insomnia disorder, will be randomized to a brief, hybrid version of CBT-I or sleep education therapy over a 4-week period, before surgery. The CBT-I will focus on the two components which have shown the highest efficacy for sleep improvement, sleep restriction therapy and stimulus control. The CBT-I treatment will be administered in self-guided digital format with addition of telehealth video-consultations with a psychologist one time per week. The sleep education therapy will also be provided in a hybrid format, including digital sessions and video-consultations with a research nurse. There will also be a booster session 1-2 weeks postoperative for both interventions. Participants will be carefully evaluated during on-site visits two times preoperative, pre- and post-intervention, and one time 6 months postoperative. During on-site visits, participants will complete multiple questionnaires (covering pain, pain catastrophizing, mental health, physical function, activity etc), undergo digital cognitive testing, quantitative sensory testing (QST, to determine pain detection thresholds to different stimuli, assess temporal summation, pain inhibitory capacity), provide blood samples, and initiate actigraphy (objective assessment of sleep continuity measures). In addition to the on-site visits, participants will complete questionnaires remotely 3 and 12 months after surgery.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Martin F Bjurström, MD, PhD; Phone Number: +46739512728; Email: martin.flores.bjurstrom@uu.se

Study Locations

• Sweden
  • Uppland
    • Uppsala, Uppland, Sweden, 75185
      • Recruiting
      • Department of Surgical Sciences, Uppsala University
      • Contact: Andrea Niklasson, M.D.; Phone Number: 0046186122110; Email: andrea.niklasson@gmail.com
      • Principal Investigator: Martin F Bjurström, Associate Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• age ≥18 years
• insomnia severity index score >10
• fulfill DSM-V criteria for persistent insomnia disorder
• average pain numerical rating scale (NRS) score ≥4 (scale 0 - 10) and/or movement-related pain NRS score ≥4 after 5 minutes walking
• scheduled to undergo primary (first-time, i.e., not revision surgery) TKA or THA due to osteoarthritis

Exclusion Criteria:

• uncontrolled medical disorders
• nightshift work
• ongoing major depressive disorder, bipolar disorder, psychotic disorder, substance dependence
• current history or high likelihood of primary sleep disorders (other than insomnia), including obstructive sleep apnea syndrome, narcolepsy, nocturnal myoclonus
• severely impaired vision (precluding ability to take part of study interventions)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cognitive behavioral therapy for insomnia (CBT-I); The CBT-I treatment will be administered in self-guided digital format over 4 weeks with addition of telehealth video-consultations with a psychologist one time per week. The CBT-I will focus on sleep restriction therapy and stimulus control, which have shown the highest efficacy for sleep improvement among components typically incorporated. A booster session will be provided 1-2 weeks postoperative.	Behavioral: Cognitive behavioral therapy for insomnia (CBT-I); Hybrid CBT-I (self-guided digital format focusing on sleep restriction therapy and stimulus control + telehealth video-consultations with psychologist)
Active Comparator: Sleep education therapy (SET); The sleep education therapy will be administered in self-guided digital format over 4 weeks with addition of telehealth video-consultations with a research nurse one time per week. The SET will focus on sleep physiology, different sleep disturbances and sleep hygiene measures. A booster session will be provided 1-2 weeks postoperative.	Behavioral: Sleep education therapy (SET); Self-guided digital sleep education (sleep hygiene, sleep physiology, sleep disturbances etc) + telehealth video-consultations with research nurse

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute postoperative pain intensity	Average pain intensity (NRS 0 - 10) over the past 24 h rated each morning, averaged over 7 days	First 7 postoperative days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity 6 months postoperative	Average pain intensity (NRS 0 - 10) over the past 24 h rated each morning, averaged over 7 days	6 months postoperative
Change in pain measures from baseline	BPI pain severity and pain interference score, QoR-15 pain score, WOMAC OA pain score	Up to 12 months postoperative
Pre- and acute postoperative change in sleep measures from baseline	insomnia severity index, Pittsburgh sleep quality index, actigraphic sleep continuity measures (sleep onset latency, total sleep time, wakefulness after sleep onset, sleep efficiency)	Up to 2 weeks postoperative
Acute postoperative opioid consumption	Oral morphine mg equivalents (OMEQs)	Postoperative day (POD) 1 and POD1-7
Recovery in the acute postoperative phase	Quality of recovery (QoR) 15 score	First 7 postoperative days
Changes in quantitative sensory testing (QST) measures of pain	Pressure pain threshold, temporal summation, conditioned pain modulation, cold pressor test	Up to 6 months postoperative
Change in cognitive function	Digital cognitive testing (Mindmore platform) incl. memory, attention and processing speed, executive functions	Up to 6 months postoperative
Change in quality of life	EuroQol 5 dimension 5 level (EQ-5D-5L), RAND-36	Up to 6 months postoperative
Change in health-related function	EQ-5D-5L, RAND-36	Up to 6 months postoperative
Change in osteoarthritis-related symptoms	WOMAC OA	Up to 12 months postoperative
Long-term postoperative sleep quality	insomnia severity index	Up to 12 months postoperative
Postoperative objective sleep continuity	actigraphic sleep efficiency [SE]	Up to 6 months postoperative
Change in anxiety from baseline	Generalized anxiety disorder 7 (GAD-7) score	Up to 6 months postoperative
Change in depression from baseline	Patient health questionnaire 9 (PHQ-9) score	Up to 6 months postoperative

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in physical activity	International physical activity questionnaire short form (IPAQ-sf)	Up to 6 months postoperative
Change in pain catastrophizing	Pain catastrophizing scale (PCS)	Up to 6 months postoperative
Change in kinesiophobia	Tampa scale of kinesiophobia (TSK)	Up to 6 months postoperative
Change in subjective pain sensitivity	Pain sensitivity questionnaire (PSQ)	Up to 6 months postoperative
Changes in blood biomarkers	Inflammatory mediators, monoamine metabolites, coagulation system etc	Up to 6 months postoperative
Fibromyalgia severity score	Sum of widespread pain index + symptom severity scale (ACR 2016)	Up to 6 months postoperative
Pain-related acceptance	Chronic pain acceptance questionnaire (CPAQ-8)	Up to 6 months postoperative

Collaborators and Investigators

• Sponsor: Uppsala University
• Investigators: Principal Investigator: Martin F Bjurström, MD, PhD, Uppsala University / Uppsala University Hospital

Publications and helpful links

General Publications

• Bjurstrom MF, Bothelius K, Maathz P, Jernelov S, Kraepelien M, Rosenstrom AHC, Niklasson A, Smith MT, Olmstead R, Irwin MR, Finan PH, Kosek E. Randomised, controlled clinical trial evaluating the effects of preoperative insomnia treatment on postoperative pain control and recovery: a protocol for the Promoting Sleep to Alleviate Pain-Arthroplasty (PROSAP-A) trial. BMJ Open. 2025 Jul 30;15(7):e099785. doi: 10.1136/bmjopen-2025-099785.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2025
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: November 17, 2023
• First Submitted That Met QC Criteria: November 17, 2023
• First Posted (Actual): November 24, 2023

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: osteoarthritis; total hip arthroplasty; insomnia; total knee arthroplasty; postoperative pain; sleep disturbance
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Mental Disorders; Pathologic Processes; Arthritis; Joint Diseases; Rheumatic Diseases; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Osteoarthritis; Osteoarthritis, Knee; Parasomnias; Sleep Initiation and Maintenance Disorders; Postoperative Complications; Osteoarthritis, Hip; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Cognitive Behavioral Therapy
• Other Study ID Numbers: Dnr 2023-03976-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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