Optimization of Obesity for Total Knee Replacement With Glucagon-like Peptide-1 Receptor Agonist

NCT06807970 | Not Yet Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: UW24-423
• Study Type: interventional
• Target: 54
• Locations: 0 countries
• Sites: N/A

Brief Summary

Studies have shown that obese patients undergoing total knee replacement (TKR) surgery face a higher risk of perioperative issues such as increased use of pain medication, surgical site infections, and the need for revision surgeries compared to non-obese patients. Obesity is also linked to more significant preoperative pain and lingering symptoms post-surgery. Consequently, there's a growing interest in weight loss interventions prior to TKR to enhance perioperative care and outcomes. Recent retrospective studies have indicated that such interventions can improve physical function post-TKR. Research focusing on weight loss interventions before joint replacement surgery is limited. There is currently a gap in research regarding RCTs on weight loss interventions using anti-obesity drugs before TKR, particularly in Asian populations. One promising avenue under exploration involves the use of glucagon-like peptide 1 receptor agonists (GLP-1RAs) as anti-obesity medication before total knee replacement (TKR) surgery. However, there are currently no randomized controlled trials (RCTs) examining the effects of GLP-1RAs on knee arthroplasty outcomes. Large database studies have indicated that GLP-1RAs may decrease the likelihood of certain post-surgery complications but increase the risk of others. In summary, addressing obesity through weight loss interventions, particularly with GLP-1RAs, holds promise for improving outcomes in TKR patients. However, further research, including randomized controlled trials, is necessary to fully understand the effects of GLP-1RAs on perioperative outcomes and patient health.

Conditions

Osteoarthritis (OA) of the Knee

Keywords

osteoarthritis

Outcome Measures

Primary Outcomes (1)

• Pain

  Assess at enrolment, prior to and after TKR, and at each follow-up till 12 months. Pain is chosen as the primary outcome because up to 14 patients in weight loss groups (versus 2 patients in control groups) in previous studies chosen to decline/delay TKR due to pain relief, suggesting a prominent effect of weight optimization on pain relief. Pain is evaluated using two approaches. The first method is visual analog scale which involves the numeric rating scale, which ranges from 0 to 10, with 0 representing no pain and 10 representing the most intense pain. The second method involves monitoring analgesic consumption, with higher consumption indicating more severe pain.

  As part of the standard of care when undergoing TKR, patients are routinely assessed at enrolment, 1 month and same day before surgery, and at 6 weeks,3 months, 6 months and 12 months post-surgery.

Secondary Outcomes (9)

• A composite score of clinical situation

  As part of the standard of care when undergoing TKR, patients are routinely assessed at enrolment, 1 month and same day before surgery, and at 6 weeks,3 months, 6 months and 12 months post-surgery.

• Length of stay

  As part of the standard of care when undergoing TKR, patients are routinely assessed at enrolment, 1 month and same day before surgery, and at 6 weeks,3 months, 6 months and 12 months post-surgery.

• Body weight

  As part of the standard of care when undergoing TKR, patients are routinely assessed at enrolment, 1 month and same day before surgery, and at 6 weeks,3 months, 6 months and 12 months post-surgery.

• Radiological parameters

  As part of the standard of care when undergoing TKR, patients are routinely assessed at enrolment, 1 month and same day before surgery, and at 6 weeks,3 months, 6 months and 12 months post-surgery.

• height

  As part of the standard of care when undergoing TKR, patients are routinely assessed at enrolment, 1 month and same day before surgery, and at 6 weeks,3 months, 6 months and 12 months post-surgery.

Study Arms (2)

GLP-1RA

EXPERIMENTAL

Intervention group: GLP-1RA +TKR: Patients in intervention group will have GLP-1RA semaglutide for 48 weeks and then stops for one month before and after TKR following the latest anesthesia guideline for GLP-1RA. Followed by TKR They will continue semaglutide for 48 weeks during the post-operative follow-up period. This is decided based on balancing treatment effect of semaglutide, waiting time for TKR, and TKR follow-up requirement. In Hong Kong, waiting time for TKR would be \~4 years and so a period of 12 months treatment of semaglutide is reasonable. And in the STEP 6 trial, weight loss at week 52 (-12%) is similar to that in study end at week 68(-13·2%), and STEP5 trial showed maintaining semaglutide to week 104 could maintain weight loss of similar degree as in week 52. And the consensus of assessing TKR Patient-Reported Outcome Measures (PROMs) is one year follow up.

Drug: Glucagon-like peptide-1 receptor agonists (GLP 1 RA)

Control (standard treatment)

PLACEBO COMPARATOR

Control Group: TKR alone: If patients are randomized to the control group, they will receive routine follow-up with general advice on diet and physical activity but will not receive semaglutide, and will not be offered a specific management program for their weight. This is in line with current practice.

Other: Control (Standard treatment)

Interventions

Glucagon-like peptide-1 receptor agonists (GLP 1 RA) DRUG

Patients in intervention group will have GLP-1RA semaglutide for 48 weeks and then stops for one month before and after TKR following the latest anesthesia guideline for GLP-1RA. Followed by TKR They will continue semaglutide for 48 weeks during the post-operative follow-up period. This is decided based on balancing treatment effect of semaglutide, waiting time for TKR, and TKR follow-up requirement. In Hong Kong, waiting time for TKR would be \~4 years and so a period of 12 months treatment of semaglutide is reasonable. And in the STEP 6 trial, weight loss at week 52 (-12%) is similar to that in study end at week 68(-13·2%), and STEP5 trial showed maintaining semaglutide to week 104 could maintain weight loss of similar degree as in week 52. And the consensus of assessing TKR Patient-Reported Outcome Measures (PROMs) is one year follow up.

GLP-1RA

Control (Standard treatment) OTHER

If patients are randomized to the control group, they will receive routine follow-up with general advice on diet and physical activity but will not receive semaglutide, and will not be offered a specific management program for their weight. This is in line with current practice.

Control (standard treatment)

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 40 and 80 years old
• BMI ≥27 kg/m2
• On the surgical waiting list for primary TKR
• Willing and able to cooperate in a weight management programme.
• Meeting indication for semaglutide

You may not qualify if:

• Revision surgery or surgery for neoplastic disease
• A medical condition which in the opinion of the investigators makes the patient unsuitable for participation in the trial
• Contraindication to GLP-1RA, like history of pancreatitis, severe gastrointestinal diseases such as gastroparesis, thyroid cancer, and inflammatory bowel disease
• Lack of acceptance of the randomisation process.

Sponsors & Collaborators

• The University of Hong Kong: lead

MeSH Terms

Conditions

Osteoarthritis

Interventions

Glucagon-Like Peptide-1 Receptor Agonists

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Hypoglycemic Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Lawrence Lau, FRCS, PhD

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lawrence Lau, FRCS, PhD

CONTACT

+852 92646862; laucml@hku.hk

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: January 15, 2025
• First Posted: February 4, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: September 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share