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Cryoneurolysis for the Management of Chronic Pain in Patients With Knee Osteoarthritis

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ClinicalTrials.gov Identifier: NCT03774121
Recruitment Status : Recruiting
First Posted : December 12, 2018
Last Update Posted : September 18, 2020
Sponsor:
Collaborator:
Odense University Hospital
Information provided by (Responsible Party):
Niels-Peter Brøchner Nielsen, PhD, Hospital of South West Jutland

Brief Summary:
Pain is the principal symptom in knee osteoarthritis (OA) and results in a considerable amount of years lived with disability, emotional distress and has significant socioeconomic consequences. Conservative treatment options, such as exercise, often fail to provide long-term pain relief and alternatively patients may be subjected to total knee arthroplasty. More than 20% of these patients experience persistent and unchanged pain post-surgery. Novel advances in the field of cryoneurolysis applies low temperatures to disrupt nerve signaling at the painful area and a recent study showed that it was possible to target the peripheral nerves in the knee and provide significant pain relief in patients with knee OA. This could potentially improve the efficacy of other therapies such as exercise, delaying or perhaps avoiding surgical intervention and improving quality of life in OA patients considerably. Further prospective randomized controlled studies are needed to confirm the effects of cryoneurolysis treatment in patients with knee OA. The primary objective of the current project is to determine the effectiveness of cryoneurolysis in its ability to decrease pain in patients with knee OA. The secondary objective is to evaluate the safety and effectiveness of cryoneurolysis in its ability to improve outcomes in the GLA:D program to potentially delay or avoid surgical intervention. 90 individuals with knee OA in the knee will be randomly allocated in either a cryoneurolysis intervention group or a sham group. Both groups will be assessed at baseline, post intervention and at 3, 6, 12 and 24 months after completion of GLA:D. The patients, therapists and data-manager will be blinded to the allocation. The primary outcome will be VAS knee pain intensity score, measured post cryoneurolysis treatment. Secondary outcome measures include functional performance, PRO-data (KOOS, EQ5D), analgesic use, a socio-economic evaluation and adverse effects.

Condition or disease Intervention/treatment Phase
Chronic Pain Osteoarthritis, Knee Device: Cryoneurolysis Other: Neuromuscular exercise (GLA:D) Device: Sham Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Cryoneurolysis for the Management of Chronic Pain in Patients With Knee Osteoarthritis; A Randomized Controlled Study
Actual Study Start Date : June 26, 2019
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: CRYO
Subjected to Cryoneurolysis treatment and Neuromuscular training (GLA:D).
Device: Cryoneurolysis
A cryoprobe will be inserted percutaneously and freeze the target nerves (infrapatellar branch of the saphenous nerve & anterior femoral cutaneous nerve) guided by ultrasound visualization.
Other Name: Cryoablation

Other: Neuromuscular exercise (GLA:D)
The GLA:D program, is a standard education and exercise program for patients with osteoarthritis in Denmark. The program is performed in groups and with the supervision of an experienced physiotherapist specialized in training of musculoskeletal disorders.

Sham Comparator: SHAM
Subjected to similar procedures as CRYO, but without freezing temperatures. Subjected to Neuromuscular training (GLA:D).
Other: Neuromuscular exercise (GLA:D)
The GLA:D program, is a standard education and exercise program for patients with osteoarthritis in Denmark. The program is performed in groups and with the supervision of an experienced physiotherapist specialized in training of musculoskeletal disorders.

Device: Sham
The sham intervention includes a similar procedure but without freezing temperatures.




Primary Outcome Measures :
  1. Change in NRS knee pain intensity score [ Time Frame: Change in NRS pain score, between baseline and immediately post surgery ]
    NRS consists of a numerical, from 0 to 10, anchored by two verbal descriptors, "no pain" for the score of zero and "worst pain imaginable" for the score of 10. NRS is a self-reported tool where the respondent is asked their current pain intensity.


Secondary Outcome Measures :
  1. Change in Pain location [ Time Frame: Change between baseline and 3, 12 an 24 month after completion of GLA:D ]
    Pain location as drawn by the patient.

  2. Change in Functional Performance Evaluated by the 30 second chair-stand test. [ Time Frame: Change between baseline and 3, 12 an 24 month after completion of GLA:D ]
    The outcome is the total number of complete chair stands performed for the duration of the task (one chair stand represents a stand followed by a sit movement).

  3. Change in use of Analgesics [ Time Frame: Change between baseline and 3, 12 an 24 month after completion of GLA:D ]
    Use of analgesics from medical records

  4. Number of Adverse effects [ Time Frame: Reported adverse effects immediately after surgery and at 3, 12 an 24 month after completion of GLA:D ]
    Pre-defined and unexpected adverse effects

  5. Change in Pain type [ Time Frame: Change between baseline and 3, 12 an 24 month after completion of GLA:D ]
    Change in pain type using prespecified pain definitions

  6. Change in Functional Performance Evaluated by the 40m fast-paced walk test. [ Time Frame: Change between baseline and 3, 12 an 24 month after completion of GLA:D ]
    The outcome is expressed as speed. i.e. walking distance (40m) divided by the time to perform the task (s).

  7. Change in Functional Performance Evaluated by the 9 step stair test. [ Time Frame: Change between baseline and 3, 12 an 24 month after completion of GLA:D ]
    The outcome is the total time to perform the task (s).

  8. Change in Functional Performance Evaluated by Maximum Voluntary Contraction [ Time Frame: Change between baseline and 3, 12 an 24 month after completion of GLA:D ]
    As measured in moment force of the knee extensors (Nm)

  9. Change in Quality of Life using the Quality of Life questionnaire (EQ5D) [ Time Frame: Change between baseline and 3, 12 an 24 month after completion of GLA:D ]
    EQ5D consists of 5 subscales; Mobility, Self-care, Usual activities, Pain/Discomfort and Anxiety / depression. An health state score is obtained based on the responses from 1-5 in each subscale, from which a single index value is calculated representing patients' overall health state.

  10. Change in self-rated health using the Quality of Life questionnaire (EQ5D) [ Time Frame: Change between baseline and 3, 12 an 24 month after completion of GLA:D ]
    EQ5D includes a so called EQ VAS score which is the patients' self-rated health on a 20 cm vertical, visual analogue scale with endpoints labelled "the best health you can imagine" and "the worst health you can imagine".

  11. Change in the subscale "Pain" using the Knee injury and Osteoarthritis Score (KOOS score) [ Time Frame: Change between baseline and 3, 12 an 24 month after completion of GLA:D ]
    KOOS consists of 5 subscales; Pain, other Symptoms, Function in daily living (ADL), Function in sport and recreation (Sport/Rec) and knee related Quality of life (QOL). A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) us calculated for each subscale.

  12. Change in the subscale "other Symptoms" using the Knee injury and Osteoarthritis Score (KOOS score) [ Time Frame: Change between baseline and 3, 12 an 24 month after completion of GLA:D ]
    KOOS consists of 5 subscales; Pain, other Symptoms, Function in daily living (ADL), Function in sport and recreation (Sport/Rec) and knee related Quality of life (QOL). A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) us calculated for each subscale.

  13. Change in the subscale "Function in daily living (ADL)" using the Knee injury and Osteoarthritis Score (KOOS score) [ Time Frame: Change between baseline and 3, 12 an 24 month after completion of GLA:D ]
    KOOS consists of 5 subscales; Pain, other Symptoms, Function in daily living (ADL), Function in sport and recreation (Sport/Rec) and knee related Quality of life (QOL). A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) us calculated for each subscale.

  14. Change in the subscale "Function in sport and recreation (Sport/Rec)" using the Knee injury and Osteoarthritis Score (KOOS score) [ Time Frame: Change between baseline and 3, 12 an 24 month after completion of GLA:D ]
    KOOS consists of 5 subscales; Pain, other Symptoms, Function in daily living (ADL), Function in sport and recreation (Sport/Rec) and knee related Quality of life (QOL). A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) us calculated for each subscale.

  15. Change in the subscale "Knee related Quality of Life (QoL)" using the Knee injury and Osteoarthritis Score (KOOS score) [ Time Frame: Change between baseline and 3, 12 an 24 month after completion of GLA:D ]
    KOOS consists of 5 subscales; Pain, other Symptoms, Function in daily living (ADL), Function in sport and recreation (Sport/Rec) and knee related Quality of life (QOL). A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) us calculated for each subscale.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Referred to GLA:D by a physician.
  • Age ≥ 18y
  • Chronic knee pain for a minimum duration of 6 months.
  • Pain intensity ≥ 40mm on a 100mm visual analogue scale (VAS).
  • Radiographic confirmation of osteoarthritis; Grade 2-4 changes according to the Kellgren Lawrence classification system
  • A decrease of ≥ 50 % in VAS scores with diagnostic genicular nerve block.
  • Written and oral understanding of Danish.

Exclusion Criteria:

  • History of systemic inflammatory conditions such as rheumatoid arthritis.
  • Previous recipient of cryoneurolysis for the knee.
  • Use of hyaluronic acid within the previous 30 days.
  • Injection of corticosteroid within the previous 3 months.
  • Clinical significant structural abnormities affecting locomotion and knee function aside from osteoarthritis and which might cause chronic knee pain.
  • Body mass index ≥ 18 and ≤ 40 kg/m
  • In treatment for other pain conditions.
  • Pregnancy
  • Coagulopathy
  • Uncontrolled serious disease (cancer, diabetes, etc.)
  • Disease associated with reactions to cold, such as cryoglobulinemia, cold urticarial and Renaud's syndrome.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03774121


Contacts
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Contact: Niels-Peter B Nielsen, PhD 004520612033 ext 004520612033 Niels-Peter.Brochner.Nielsen@rsyd.dk
Contact: Bibi (Valgerdur) Gram, PhD 004520612033 ext 004520612033 bibi.valgerdur.gram@rsyd.dk

Locations
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Denmark
Hospital of Southwest Jutland Recruiting
Esbjerg, Region Of Southern Denmark, Denmark, 6700
Contact: Niels-Peter Brøchner Nielsen, PhD    20612033    niels-peter.brochner.nielsen@rsyd.dk   
Sponsors and Collaborators
Hospital of South West Jutland
Odense University Hospital
Investigators
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Study Director: Bibi (Valgerdur) Gram, PhD Hospital of South West Denmark
Study Director: Carsten Kock-Jensen, MD Hospital of South West Denmark
Principal Investigator: Niels-Peter B Nielsen, PhD Hospital of South West Denmark
Publications:

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Responsible Party: Niels-Peter Brøchner Nielsen, PhD, Post doc, Research employee, Hospital of South West Jutland
ClinicalTrials.gov Identifier: NCT03774121    
Other Study ID Numbers: CryoKnee01
First Posted: December 12, 2018    Key Record Dates
Last Update Posted: September 18, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Niels-Peter Brøchner Nielsen, PhD, Hospital of South West Jutland:
Cryoneurolysis
Exercise
Pain
Physical capacity
Additional relevant MeSH terms:
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Osteoarthritis
Osteoarthritis, Knee
Chronic Pain
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Pain
Neurologic Manifestations