Clinical trial NCT04542655: The Effect of Exercise on Serum Levels of Collagen and Proteoglycan in Patients With Knee Osteoarthritis (EFEX-OA-01)
Official title: An Open-label, Single-center, Randomized, Controlled, Exploratory Study to Investigate the Effect of Weight Bearing Versus Non-weight Bearing Exercise on Collagen and Proteoglycan in Serum and Urine in Patients With Osteoarthritis and Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Osteoarthritis, Knee
Lead sponsor: Nordic Bioscience A/S
Sponsor class: INDUSTRY
Collaborators: name: University of Copenhagen
name: NBCD A/S
First posted: 2020-09-09
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants will be randomized to an order of exercise-intervention: cycling, running. This will be followed by a resting intervention. Interventions are planned 1 week apart.

Blood will be sampled before, immediately after and again at 1, 2, 3 and 24 hours after intervention start. Spot urine is sampled before, after and the next day.
Primary purpose: BASIC_SCIENCE

Brief summary: Aim of EFEX-OA-01: To explore how running, cycling and resting acutely influence levels of collagen and proteoglycan in patients with osteoarthritis knee and in young healthy subjects, as reflected by changes in serum and urine biochemical markers originating from joint related collagens and proteoglycans.


Eligibility criteria: Inclusion criteria for OA patients:

1. Kellgren-Lawrence radiological grade of 1-3 in at least one tibio-femoral joint diagnosed by screening x-ray.
2. 35 to \< 75 years of age at the time of signing the informed consent form.
3. Bodyweight \> 50 and \< 150 kg and a BMI in the range 18,5-35 kg/m2.
4. Are male or female.
5. Is able to meet for all of the four study visits and comply with the dietary and activity restrictions.
6. Can give informed consent.

Exclusion criteria for OA patients:

Medical conditions:

1. History of arthroscopy or intra-articular administration of corticosteroids or hyaluronic acid into the target knee within 6 months before screening.
2. Kellgren-Lawrence radiological grade of 4 in at least one tibio-femoral joint
3. Previous arthroplasty of knee or hip.
4. Intention of having major surgery during the timeframe of this study.
5. OA related to eg. dysplasia, aseptic osteonecrosis, acromegaly, Paget disease, Stickler syndrome, hemochromatosis, gout, chondrocalcinosis (pseudogout) or calcium pyrophosphate deposition disease.
6. Current treatment with beta-receptor adrenergic antagonists (beta-blockers), systemic corticosteroid treatment in doses equivalent to \> 10 mg of prednisolone per day, or Vitamin K antagonists, new oral anticoagulants, fractionated and non-fractionated heparin
7. Active systemic infection.
8. Active systemic inflammatory or autoimmune disease.
9. Symptomatic occlusive arterial disease e.g. claudication intermittens.
10. Heart failure \> NYHA class II.
11. History of transient ischaemic attack or stroke.
12. ECG findings which, in the opinion of the investigator, compromises patient safety related to HRmax-test.
13. History of coronary artery disease, myocardial infarction, or other serious cardiovascular disease, as evaluated by the investigator.
14. Is not currently active athlete or a highly trained individual.

Inclusion criteria for healthy subjects:

1. 18 to \< 75 years of age at the time of signing the informed consent form.
2. Have a bodyweight within \> 50 and \< 150 kg and a BMI within the range 18,5-35 kg/m2.
3. Are male or female.
4. Is able to meet for all of the four study visits and comply with the dietary and activity restrictions.
5. Can give informed consent.

Exclusion criteria for healthy subjects:

1. History of arthroscopy or intra-articular administration of corticosteroids or hyaluronic acid into the target knee within 6 months before screening.
2. Previous arthroplasty of knee or hip.
3. Intention of having major surgery during the timeframe of this study.
4. Secondary OA e.g. because of dysplasia, aseptic osteonecrosis, acromegaly, Paget disease, Stickler syndrome, hemochromatosis, gout, chondrocalcinosis (pseudogout) or calcium pyrophosphate deposition disease.
5. Current treatment with beta-receptor adrenergic antagonists (beta-blockers), systemic corticosteroid treatment in doses equivalent to \> 10 mg of prednisolone per day, or Vitamin K antagonists, new oral anticoagulants, fractionated and non-fractionated heparin
6. Any known active systemic infection.
7. Any known active systemic inflammatory or autoimmune disease.
8. Symptomatic occlusive arterial disease e.g. Inermittent claudication.
9. Heart failure \> NYHA class II.
10. History of transient ischaemic attack or stroke.
11. History of coronary artery disease, myocardial infarction, or other serious cardiovascular disease, as evaluated by the investigator.
12. ECG findings which, in the opinion of the investigator, compromises patient safety related to HRmax-test.
13. Is not currently active athlete or a highly trained individual.
14. X-ray verified Kellgren-Lawrence grade 1-4.
15. Is clinically suspected of having hip OA.

Other exclusions (all subjects):

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. Are 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 24 hours prior to study intervention.
5. Other factors e.g. self-reported drug abuse, which in the opinion of the investigator may interfere with the study conduct.
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

Primary outcomes:
measure: Changes in biomarkers (exploratory)
timeFrame: Acute: 0-4 hours and subacute: 24 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Herlev
country: Denmark
facility: Sanos Clinic
Study officials:
affiliation: Sanos Clinic
name: Henning Nielsen, MD, DMSci
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bjerre-Bastos JJ, Nielsen HB, Andersen JR, Karsdal M, Boesen M, Mackey AL, Byrjalsen I, Thudium CS, Bihlet AR. A biomarker perspective on the acute effect of exercise with and without impact on joint tissue turnover: an exploratory randomized cross-over study. Eur J Appl Physiol. 2021 Oct;121(10):2799-2809. doi: 10.1007/s00421-021-04751-z. Epub 2021 Jun 22.