Exercise in Patients With Hypermobile Joints and Knee Pain (HIPEr-Knee)

High-load Resistance Training Compared With Usual Care for Treatment of Painful Knee Joint Hypermobility in Young Adults: A Randomised Controlled Trial (the HIPEr-Knee Study)

Pain associated with knee joint hypermobility is common in the adult population, but evidence on treatment is sparse. This study investigates if high-load resistance training is superior to usual care in improving activity-related pain in young patients (18-45 years) with hypermobile joints and knee pain.

Study Overview

• Status: Not yet recruiting
• Conditions: Knee Discomfort; Hypermobility, Joint; Hypermobility Syndrome
• Intervention / Treatment: Other: High-load strength training for the knee; Other: Neuromuscular training for the knee

Detailed Description

Knee joint hypermobility is common in the adult population. Patients with knee joint hypermobility and knee pain are typically managed with low intensity resistance training and proprioceptive training to reduce knee pain and improve function, but many patients do not respond well to these treatment strategies. High-load resistance training offers additional benefits to low intensity resistance training, including marked increase in muscle cross-sectional area, neural drive, and increased tendon stiffness, all important components of acquiring active knee joint stability during movement tasks and daily life. Therefore, the primary aim of this randomised controlled trial (RCT) is to investigate if high-load resistance training is superior to usual care in reducing activity-related pain in young patients (18-45 years) with hypermobile joints and knee pain.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Behnam Liaghat, PhD; Phone Number: +4526826801; Email: bliaghat@health.sdu.dk

Study Locations

• Denmark
  • Fyn
    • Odense, Fyn, Denmark, 5000
      • Physiotherapy Clinics Region of Southern Denmark
      • Contact: Behnam Liaghat, PhD; Phone Number: +4526826801; Email: bliaghat@health.sdu.dk
    • Odense, Fyn, Denmark, 5230
      • University of Southern Denmark
      • Contact: Behnam Liaghat, PhD; Phone Number: +4526826801; Email: bliaghat@health.sdu.dk

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria

• Persistent knee pain for ≥ 3 months (self-reported)
• Knee pain ≥ 30mm during the last week using a 0-100 mm visual analogue scale (VAS; 0=no pain and 100=worst imaginable pain) (self-reported)
• Generalised joint hypermobility assessed with the Five-Part Hypermobility Questionnaire (positive ≥ 2/5) (self-reported)
• Local knee joint hypermobility using the passive hyperextension of the knee in standing (positive > 10 degrees of hyperextension) and confirmed in supine lying (heel resting on 20 cm high block on the bench surface), with passive knee hyperextension (positive > 10 degrees) (objectively measured)

Exclusion criteria

• Diagnosed with patellar tendinopathy
• Pregnancy or childbirth within the past year (due to increased levels of relaxin that could affect joint stability)
• Knee surgery within the past year
• Participation in regular structured resistance training within the past six months
• Inability to speak and understand Danish.
• All types of Ehlers-Danlos syndrome
• Other heritable connective tissue disorders such as Marfan syndrome, osteogenesis imperfecta, Loeys-Dietz syndrome, Stickler syndrome, skeletal dysplasias
• Autoimmune rheumatic connective tissue disorders such as lupus, rheumatoid arthritis; Chromosomal conditions such as Fragile X syndrome, Kabuki syndrome, Down syndrome
• Neuromuscular disorders that can cause joints to become unstable, such as multiple sclerosis

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Progressive high-load resistance training program performed twice weekly for 12 weeks	Other: High-load strength training for the knee; The exercise programme includes exercises identified in literature to target muscles around the knee.
Active Comparator: Standard care; The standard care group will receive instructions on a neuromuscular training program with focus on knee stability and function performed at low intensities to be conducted twice weekly for 12 weeks	Other: Neuromuscular training for the knee; The exercise programme includes exercises identified in literature to target muscles around the knee.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analogue Scale Nominated Activity	The primary outcome is the Self-reported knee pain during an activity nominated by patients to be the most aggravating for their present knee pain (VAS nominated activity - VASNA, 0-100, 100 = worse). The primary endpoint is at 12-week follow-up.	Baseline, 6 weeks, 12 weeks (primary endpoint), 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee injury and Osteoarthritis Outcome Score (KOOS)	Knee injury and Osteoarthritis Outcome Score is a validated knee-specific questionnaire used to assess patient-reported outcomes in the continuum from knee injury to osteoarthritis and is widely used for different types of knee pathology. (0-100, 100 = best)	Baseline, 12 weeks, 12 months
Adverse events	Adverse events will be defined as any unintended, negative findings, symptom, or illnesses that occur during the study assessments or interventions, whether attributable to the project or not.	Up to 12 months
Dynamic knee strength	Dynamic leg strength will be established by a 5-repetition maximum leg press (single leg) by a standardised protocol.	Baseline, 12 weeks
Knee reposition sense	Sitting active knee joint reposition (proprioception) test will be performed using a HALO Digital Goniometer, to assess mean absolute angle error (AAE)	Baseline, 12 weeks
Single-Leg-Hop for Distance	The patients will be instructed to hop forward as far as possible and land steadily and stand still for at least three seconds.	Baseline, 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee pain past week	Knee pain for the past week is measured using the Visual Analogue Scale (0-100, 100 = worse)	Baseline, 6 weeks, 12 weeks, 12 months
Tampa scale of Kinesiophobia (TSK) 11 item	Tampa scale of Kinesiophobia is used to measure impression of change in fear of movement from baseline to 16 weeks follow-up. It consists of an 11-item scale where each question is scored on a 4 point Likert scale, with 1 indicating, "strongly disagree" and 4 indicating, "strongly agree". The total scores range from 11-44, with higher scores representing increased fear of movement.	Baseline, 12 weeks, 12 months
EQ-5D-5L	the European Quality of life-5 Dimensions-5-Level measures change in health related quality of life and includes the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D descriptive system comprises five dimensions (mobility, Self-care, usual activities, pain/discomfort and anxiety/depression). Each dimension is rated using a five-level ordinal scale from no problems to extreme problems. It results in a preference based index that range from states worse than death (<0), to 1 (full health), anchoring dead at 0. A score of one indicates that the participants perceived their health at the best possible state and a score below null that the participants perceived their health worse than death.	Baseline, 12 weeks, 12 months
EQ VAS	the European Quality of life-5 Dimensions-5-Level measures change in health related quality of life and includes the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ VAS measures change in health related quality of life. It includes a visual analogue scale where own health 'today´ is rated on a scale from 0 (worst imaginable health) to 100 (best imaginable health).	Baseline, 12 weeks, 12 months
Global perceived effect (GPE)	To measure the patients self-rated impression of improvement at follow-up the GPE will be used related to knee problems. GPE measures self-rated impression of improvement since baseline assessment on a 7-point scale (1 "worse, an important worsening" to 7 "better, an important improvement)	12 weeks, 12 months
PASS	Patient Acceptable Symptom State "When you think of your shoulder function, will you consider your current condition as satisfying? By shoulder function, you should take into account your activities of daily living, sport and recreational activities, your pain and other symptoms and your quality of life". Answered by "yes" or "no".	12 weeks, 12 months
TF	Treatment Failure Only answered by patients answering "no" to PASS. "Would you consider your current state as being so unsatisfactory that you consider the treatment to have failed?". Answered by "yes" or "no".	12 weeks, 12 months
Clinical important difference	American College of Rheumatology response criteria 20% and 50%	12 weeks, 12 months
Knee instability questions	Within the last month, have you experienced that your knee was unstable or about to give out? To what extent has the experience of your knee feeling unstable or giving out affected your daily activity level within the last month?	Baseline, 12 weeks, 12 months
Tendon stiffness	Stiffness of the patellar tendon is assessed based on corresponding values of tendon force and tendon deformation (measured by use of B-mode ultrasonography). Subgroup of patients (n = 30)	Baseline, 12 weeks
Quadriceps rate of torque development (RTD)	Rate of torque development in the quadriceps muscle. Subgroup of patients (n = 30)	Baseline, 12 weeks
Patella instability	Moving patellar apprehension test will be used to assess patella instability. Subgroup of patients (n = 30)	Baseline, 12 weeks
Quadriceps maximal voluntary isometric contraction	Isometric maximal voluntary contraction in the quadriceps muscle. Subgroup of patients (n = 30)	Baseline, 12 weeks

Collaborators and Investigators

• Sponsor: University of Southern Denmark
• Collaborators: Odense Patient Data Explorative Network; Independent Research Fund Denmark
• Investigators: Principal Investigator: Behnam Liaghat, PhD, University of Southern Denmark; Study Director: Jonas B Thorlund, PhD, University of Southern Denmark

Study record dates

Study Major Dates

• Study Start (Estimated): February 15, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: February 9, 2024
• First Submitted That Met QC Criteria: February 17, 2024
• First Posted (Actual): February 26, 2024

Study Record Updates

• Last Update Posted (Actual): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 17, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Treatment; Randomised controlled trial; Knee pain; Hypermobility
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Joint Instability
• Other Study ID Numbers: RCT_hypermobile_knee

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