Aerobic vs Neuromuscular Exercise for Knee OA

Knee Osteoarthritis Clinical Trial

— CANO  

Official title:

Comparative Effectiveness of High-intensity Aerobic Exercise and Biomechanical Neuromuscular Exercise for Treatment of Knee Osteoarthritis: A Randomised Open Label Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06170229
• Other study ID #: PT-2023-DK-3
• Status: Recruiting
• Phase: N/A
• Start date: February 23, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: February 2024
• Source: Frederiksberg University Hospital
• Contact: Marius Henriksen, PhD
• Phone: +4538164160
• Email: marius.henriksen[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study aims to compare the effects of an education and High Intensity Interval Training program (eHIIT) with the widely used Neuromuscular Exercise and education program (NEMEX-e) on knee OA symptoms and risk factors for cardiovascular disease in people with knee OA and at least one risk factor for developement of cardiovascular disease. The main research questions the study aims to answer are:

• Is the eHIIT program better than the NEMEX-e program for reducing the risk of cardiovascular disease?

• Are the two programs equally good at providing improvement in knee symptoms?

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 31, 2026
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age =18- years

• Diagnosis of tibiofemoral knee OA according to the American College of Rheumatology criteria

• Radiographically confirmed diagnosis of tibiofemoral OA based on radiographs not older than 6 months.

• Average knee pain level = 4 (0=No pain and 10=Worst pain) over the past week (7 days)

• At least one of following risk factors for development of cardiovascular disease:

• Body mass index = 30 kg/m2

• Hypertension (or in treatment of): Systolic = 135 and/or diastolic = 85 mm Hg

• Elevated HbA1c (or in treatment of): = 130.7 mg/dL (44 mmol/mol)

• Elevated Triglycerides (or in treatment of): = 150 mg/dL (1.7 mmol/L)

• Elevated Cholesterol (or in treatment of) (Low density lipides, LDL): LDL = 54 mg/dL (3.0 mmol/L)

Exclusion Criteria:

• Contraindication to exercise (e.g., resting systolic blood pressure > 200 or diastolic blood pressure > 115, acute or reoccurring chest pain)

• Unstable body weight the last 3 months (gain/loss outside +/- 5 kg)

• Planned weight loss (non-pharmacological, pharmacological, and surgical) during study participation

• Known current cancer

• Major cardiovascular event within the last 5 years

• Insulin dependent type 1 or type 2 diabetes

• Psoriatic, rheumatoid, or gouty arthritis disease

• Generalized pain syndromes such as fibromyalgia

• Lumbar or cervical nerve root compression syndromes

• Scheduled surgery during study participation

• Treatment with biological medication

• Impairments that prevent performance in high intensity aerobic exercise

• Current or planned participation in other health research intervention studies

• Pregnant/considering pregnancy

• Any other condition or impairment that, in the opinion of the investigator, makes a potential participant unsuitable for participation or which obstruct participation, such as a large knee joint effusion, uncontrolled diabetes/hypertension, psychiatric or cognitive disorders, language barriers, or opiate dependency.

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Behavioral:
• eHIIT
Education and High intensity Interval Training (Aerobic Exercise) The focus of the one educational session is rationale for aerobic exercise, expected physiological effects of aerobic exercise, diet when performing an exercise program, how the knee accommodates to exercise (including potential experience of muscle soreness and how that is different from joint pain), and management of potential knee OA symptom flares. HIIT is an aerobic exercise form. The eHITT protocol consist of eight 2-minute intervals of high intensity training (with the goal to train at a heart rate of at least 80% of HRmax) followed by 2 minutes of moderate training intensity (with the goal to train at a heart rate of at least 60% of HRmax). There will be several types of exercise modalities for aerobic exercise available (treadmills, cross-trainers, row- and cycle ergometers) and participants may choose whichever they prefer.
• NEMEX-e
Education and Neuromuscular Exercise The focus of the two educational sessions is on providing knowledge of OA and treatment options to the participants, with a special focus on knee OA, diet, and exercise and its benefits. Furthermore, advice about self-management is given. The exercises are based on neuromuscular principles to improve sensorimotor control and achieve compensatory functional stability. Sensorimotor control is the ability to coordinate muscle activity and maintain functional stability during movement allowing for joint stability during physical activity. Various positions (sitting, lying, standing) are used to achieve the desired postural activity. The overall goal is to obtain muscle control and stability in situations resembling daily life and/or more strenuous activities. The focus is on achieving good quality of the performance in each exercise with appropriate postural orientation (e.g., joint positioned appropriately in relation to each other).

Locations

Country	Name	City	State
Denmark	The Parker Institute, Frederiksberg Hospital	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Frederiksberg University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Knee-related Quality of Life	The Knee injury and Osteoarthritis Outcome Score (KOOS) quality of life subscale (KOOS-QoL), a disease-specific patient-reported instrument designed to assess knee-related quality of life in patients with knee osteoarthritis.; The KOOS-QoL subscale is scored on a 0-100 scale with 100 indicating best possible knee-related quality of life and 0 indicating worst possible knee-related quality of life.	Baseline, week 8, week 12 and week 26
Other	Knee Symptoms	The Knee injury and Osteoarthritis Outcome Score (KOOS) symptoms subscale (KOOS-symptoms), a disease-specific patient-reported instrument designed to knee symptoms in patients with knee osteoarthritis.; KOOS-symptom is scored on a 0-100 scale with indicating no symptoms and 0 indicating worst possible symptoms.	Baseline, week 8, week 12 and week 26
Other	Knee Function in Sports and Recreational activities	The Knee injury and Osteoarthritis Outcome Score (KOOS) Sports and Recreation subscale (KOOS-Sports/Recreation), a disease-specific patient-reported instrument designed to knee symptoms in patients with knee osteoarthritis.; KOOS-Sports/Recreation is scored on a 0-100 scale with indicating no symptoms and 0 indicating worst possible symptoms.	Baseline, week 8, week 12 and week 26
Other	The World Health Organisation - Five Well-Being Index (WHO-5)	Patient reported mental well-being will be obtained with the The World Health Organisation 5-Well-Being Index consisting of five questions each scored on a 0 to 5 scale.; Raw score: 0 represents worst possible well-being and 25 represents best possible well-being.; Percentage score: 0 represents worst possible well-being and 100 represents best possible well-being.	Baseline, week 8, week 12 and week 26
Other	OMERACT-OARSI treatment responder criteria	A classification of patients as a positive responder based on the Outcome Measures in Rheumatology (OMERACT) and Osteoarthritis Research Society International (OARSI) (OMERACT-OARSI) responder criteria that classifies patients according to improvements in pain (co-primary outcome),function (secondary outcome) and patient global assessment (secondary outcome).; Each participant is classified as either a "responder" or a "non-responder" at each of the post-baseline follow-ups.	Baseline, week 8, week 12 and week 26
Other	Sleep quality using the global Single-item sleep quality scale (SQS)	Sleep quality will be obtained with the global Single-item sleep quality scale (SQS). SQS is scored on 0-10 scale with 0 representing worst possible sleep quality and 10 representing best possible sleep quality.	Baseline, week 8, week 12 and week 26
Other	Nightly pain	Self-reported pain during the night is obtained on a 0-2 scale with 0=No nightly pain, 1=pain at movement or in certain positions, and 2=Pain even without movement.	Baseline, week 8, week 12 and week 26
Other	Maximal aerobic capacity (VO2 peak) during a cardiopulmonary exercise test	A cardiopulmonary exercise test will be used to assess maximal aerobic capacity (VO2peak) measured in ml/min/kg.	Baseline, week 8, week 12 and week 26
Other	Maximum work during a cardiopulmonary exercise test	The maximal work during the cardiopulmonary exercise test measured in Watts (W)	Baseline, week 8, week 12 and week 26
Other	Respiratory exchange ratio (RER) during a cardiopulmonary exercise test	The respiratory exchange ratio (RER) during the cardiopulmonary exercise test is calculated as the ratio of carbon-dioxide production (VCO2) and oxygen consumption (VO2)	Baseline, week 8, week 12 and week 26
Other	Maximal hear rate during a cardiopulmonary exercise test	The maximal heart rate during a cardiopulmonary exercise test is recorded as beats/min.	Baseline, week 8, week 12 and week 26
Other	Lean body mass from a dual x-ray absorptiometry scan	Dual x-ray absorptiometry (DXA) will be used to assess lean body mass	Baseline, Week 12 and Week 26
Other	Total fat mass from a dual x-ray absorptiometry scan	Dual x-ray absorptiometry (DXA) will be used to assess total fat mass.	Baseline, Week 12 and Week 26
Other	Bone mineral density from a dual x-ray absorptiometry scan	Dual x-ray absorptiometry (DXA) will be used to assess bone density.	Baseline, Week 12 and Week 26
Other	Hip and waist circumstance	The measurements are recorded in cm and measured during a clinical examination using a measurement tape and standardized procedures	Baseline, Week 12 and Week 26
Other	Leg extensor power	Muscle power (force × velocity) of the lower limb of the target knee will be assessed using the Nottingham power rig. In a seated position, the participants will be instructed to push with a single leg against a plate at maximal effort/force.	Baseline, Week 12 and Week 26
Other	Analgesics usage	The participants' use of over-the-counter paracetamol and ibuprofen will be recorded during an interview with an investigator.	Baseline, Week 12 and Week 26
Other	Pressure pain sensitivity	A hand-held pressure algometer will used to assess pressure pain thresholds (PPTs). Pressure will be applied at a rate of approximately 30 kilopascal per second (kPa/s), with a 1 cm2 probe. All participants are instructed to push a button when they feel that the pressure becomes just barely painful. PPTs from the medial tibiofemoral joint space on the target knee and the contralateral elbow will be assessed	Baseline, Week 12 and Week 26
Other	C-reactive protein concentration	From a blood sample	Baseline, Week 12 and Week 26
Other	Interleukin 6 (IL6) concentration	From a blood sample	Baseline, Week 12 and Week 26
Primary	Maximal oxygen consumption (VO2max)	Cardiopulmonary exercise test (CPET) on an ergometer bicycle for evaluation maximal oxygen consumption (VO2max) measured in ml/min/kg	Baseline and Week 12
Primary	Knee pain	The Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale (KOOS-pain), a disease-specific patient-reported instrument designed to assess knee pain in patients with knee osteoarthritis.; The KOOS-pain subscale is scored on a 0-100 scale with 100 indicating no pain and 0 indicating extreme pain.	Baseline and Week 12
Secondary	Maximal oxygen consumption (VO2max)	Cardiopulmonary exercise test (CPET) on an ergometer bicycle for evaluation maximal oxygen consumption (VO2max) measured in ml/min/kg	Week 8 and week 26
Secondary	Knee pain	The Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale (KOOS-pain), a disease-specific patient-reported instrument designed to assess knee pain in patients with knee osteoarthritis.; The KOOS-pain subscale is scored on a 0-100 scale with 100 indicating no pain and 0 indicating extreme pain.	Week 8 and week 26
Secondary	Body Mass	Body mass measured in kilograms using a scale	Baseline, Week 12 and Week 26
Secondary	Blood Pressure	Systolic and Diastolic blood pressure	Baseline, Week 12 and Week 26
Secondary	Triglyceride concentration	From a blood sample	Baseline, Week 12 and Week 26
Secondary	Low Density Lipids (LDL) concentration	From a blood sample	Baseline, Week 12 and Week 26
Secondary	Cholesterol concentration	From a blood sample	Baseline, Week 12 and Week 26
Secondary	Glucose concentration	From a blood sample	Baseline, Week 12 and Week 26
Secondary	HbA1c concentration	From a blood sample	Baseline, Week 12 and Week 26
Secondary	Patient Global Assessment of disease Impact	Patient-reported degree of patient's perceived impact of their knee OA on their overall life will be obtained using a 100 mm analogue scale (VAS) with anchors: 0=" No impact" and 100 = "Worst imaginable impact".	Baseline, week 8, week 12 and week 26
Secondary	Physical Functioning	The Knee injury and Osteoarthritis Outcome Score (KOOS) function subscale (KOOS-function), a disease-specific patient-reported instrument designed to assess physical functioning in patients with knee osteoarthritis.; The KOOS-function subscale is scored on a 0-100 scale with 100 indicating no functional impairments and 0 indicating extreme functional impairments.	Baseline, week 8, week 12 and week 26
Secondary	Health related quality of Life and physical and mental well-being (Short Form 12 (SF-12))	The 12-item short form health questionnaire (SF-12) is a measure of physical and mental health.; The physical health component is scored between 0-72. The mental health component is scored between 0-70. For both components 0 mean a worse outcome.	Baseline, week 8, week 12 and week 26