The Effect of Exercise on Serum Levels of Collagen and Proteoglycan in Patients With Knee Osteoarthritis (EFEX-OA-02)

An Open-label, Randomized, Cross-over Study to Investigate the Effect of Weight-bearing vs Non-weight-bearing Exercise and Cardiovascular Stress Without Load on Collagen and Proteoglycan in Serum and Urine in Patients With Osteoarthritis

The aim of EFEX-OA-02 is to explore how running, cycling, exercise simulation and resting acutely influence collagen and proteoglycan homeostasis in OA, as reflected by changes in collagen and proteoglycan levels in urine and serum.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Other: Cycling then running; Other: Inotropy; Other: Resting; Other: Running then cycling

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Cumulated Osteoarthritis Kellgren-Lawrence radiological grade of at least 2 in the tibio-femoral joints diagnosed by screening X-ray.
2. 40 to < 75 years of age at time of signing the informed consent.
3. Body weight > 50 and < 100 kg and BMI in the range 18.5-35 kg/m2 .
4. Male or female.
5. Able to attend all four study sessions and comply with the dietary and activity restrictions.
6. Able to provide informed consent

Exclusion Criteria:

Medical conditions:

1. Osteoarthritis Kellgren-Lawrence radiological grade of 4 in one or both knees.
2. Cumulated osteoarthritis Kellgren-Lawrence radiological grade no higher than 1.
3. History of arthroscopy or intra-articular administration of corticosteroids or hyaluronic acid into the target knee within 6 months before screening.
4. Previous arthroplasty of knee or hip.
5. Intention to have major surgery during the timeframe of the study.
6. Secondary OA related to e.g. any known trauma including cruciate ligament tears, meniscus tears and cartilage damage, dysplasia, aseptic osteonecrosis, acromegaly, Paget disease, Stickler syndrome, hemochromatosis, gout, chondrocalcinosis (pseudogout).
7. Current treatment with beta-receptor adrenergic antagonists (beta-blockers), MAO inhibitor, systemic corticosteroid treatment in doses equivalent to > 10 mg prednisolone per day, or vitamin K antagonists, new oral anticoagulants, fractionated and non-fractionated heparin.
8. Active systemic infection.
9. Active systemic inflammatory or autoimmune disease.
10. Any sign of previous or current cardiovascular disease.
11. Not currently an active athlete or highly trained individual.

Other exclusion criteria:

1. Legal incapacity or limited legal capacity.
2. Inability to communicate or cooperate with the investigator or to comply with the requirements of the entire study.
3. Categorized as being very difficult to draw blood from, as evaluated by the investigator.
4. Current alcohol abuse and/or inability to refrain from intake of alcoholic beverages for 24 hours prior to the study intervention.
5. Other factors, e.g. self-reported drug abuse, which in the opinion of the investigator may interfere with the performance of the study.
6. Site staff, study staff members and study staff family members.
7. Other concomitant disease compromising or otherwise significantly affecting ECM turnover in the opinion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Cycling as first intervention; Cycling -> Running -> Inotropy -> Resting	Other: Cycling then running; Ergometer cycling Treadmill running; Other Names: Exercise; Other: Inotropy; Adrenaline induced inotropy; Other Names: Exercise simulation; Other: Resting; Subjects must be minimally physically active; Other Names: Non-Ex
OTHER: Running as first intervention; Running -> Cycling -> Inotropy -> Resting	Other: Inotropy; Adrenaline induced inotropy; Other Names: Exercise simulation; Other: Resting; Subjects must be minimally physically active; Other Names: Non-Ex; Other: Running then cycling; Treadmill running Ergometer cycling; Other Names: Exercise

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute chances in biomarkers	Serum and urine biochemical markers of joint related collagens and proteoglycan (not further specified)	Acute: 0-4 hours and subacute: 24 hours

Collaborators and Investigators

• Sponsor: Nordic Bioscience A/S
• Collaborators: University of Copenhagen; NBCD A/S
• Investigators: Principal Investigator: Niels Secher, MD, DMSci, University of Copenhagen

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 8, 2020
• Primary Completion (ACTUAL): June 7, 2021
• Study Completion (ACTUAL): June 7, 2021

Study Registration Dates

• First Submitted: August 27, 2020
• First Submitted That Met QC Criteria: September 2, 2020
• First Posted (ACTUAL): September 9, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 8, 2021
• Last Update Submitted That Met QC Criteria: June 7, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: EFEX-OA-02_FINAL_Protocol_v1.2

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