Cryoneurolysis for the Management of Chronic Pain in Patients With Knee Osteoarthritis; A Randomized Controlled Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 87
- 试验地点
- 2
- 主要终点
- Change in NRS knee pain intensity score
研究概览
简要总结
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, 2 weeks post cryoneurolysis, post GLA;D and at 6, 12 and 24 month follow-up. 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.
详细描述
BACKGROUND 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. Knee OA in particular, has a high prevalence rate compared to other types of OA, and is also present in the younger working age population. The treatment of knee OA typically focuses on pain relief, however the effects of current conservative treatment options remain small to moderate and most are associated with side effects. In many cases patients alternatively may be subjected to partial/total knee arthroplasty (TKA). TKA is considered to be an effective treatment for end-stage knee osteoarthritis however more than 20% of patients receiving TKA, experience persistent and unchanged pain post-surgery. Reviewing these results, focus should be on low-risk, minimally invasive therapies. Novel advances in the field of cryoneurolysis are in that respect promising. Cryoneurolysis has made it possible to apply low temperatures to a target percutaneous peripheral nerve, causing Wallerian degeneration. This has been shown to provide pain relief in a variety of chronic pain conditions. Recently, Radnovich et al. (2017) targeted the genicular nerves to reduce pain in patients with knee OA. The authors reported significant pain relief in patients with knee OA for up to 150 days. The authors reported expected adverse effects, that were transient, with mild severity, requiring no further intervention. These results might suggest that cryoneurolysis treatment is a safe procedure, that may reduce both pain and symptoms in patients with knee OA. Further prospective randomized controlled studies, with adequate power are needed to confirm the efficacy and safety of cryoneurolysis treatment in patients with knee OA.
In Denmark, a neuromuscular exercise program (GLA:D) has been implemented, for the treatment of knee and hip OA in clinical practice. Recent studies show that exercise reduce pain and improve function in people with knee or hip OA. Despite of these reports the beneficial effects remains moderate with difficulties in maintaining these effects at long-term follow-up and includes a significant discontinuation rate for patients reporting high pain levels. In this line, pain and muscle weakness, among others, have been reported to be major barriers for physical exercise. The application of cryoneurolysis treatment as an effective pain reducing treatment prior to a standardized exercise program could perhaps provide significant pain relief, resulting in improved adherence, exercise effectiveness and long-term benefits of both therapies.
The primary objective of the current project is to determine the effectiveness of cryoneurolysis in its proposed ability to decrease pain in patients with knee osteoarthritis. 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.
We hypothesize that cryoneurolysis in combination with GLA:D will be a safe and effective therapeutic option with few side effects to reduce pain in patients with knee osteoarthritis and may post pone surgical intervention.
TRIAL DESIGN This study is a randomized, controlled, trial (RCT) designed to test the efficacy of cryoneurolysis treatment in patients with knee osteoarthritis followed by a neuromuscular exercise program (GLA:D). The patients will be randomly allocated in either a cryoneurolysis intervention group (CRYO) or a sham group (SHAM) and will be assessed at baseline, 2 weeks post cryoneurolysis, post GLA;D and at 6, 12 and 24 month follow-up. The tests will include both patient-reported outcomes (PRO) and objective functional measurements.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Change in NRS knee pain intensity score
时间窗: Change in NRS pain score, between baseline and two weeks 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.
次要结局
- Change in Functional Performance Evaluated by the 40m fast-paced walk test.(Change between baseline, 2 weeks post cryoneurolysis, post GLA;D and at 6, 12 and 24 month follow-up.)
- Change in Functional Performance Evaluated by the 30 second chair-stand test.(Change between baseline, 2 weeks post cryoneurolysis, post GLA;D and at 6, 12 and 24 month follow-up.)
- Change in Functional Performance Evaluated by Maximum Voluntary Contraction(Change between baseline, 2 weeks post cryoneurolysis, post GLA;D and at 6, 12 and 24 month follow-up.)
- Change in Pain location(Change between baseline, 2 weeks post cryoneurolysis, post GLA;D and at 6, 12 and 24 month follow-up.)
- Change in Pain type(Change between baseline, 2 weeks post cryoneurolysis, post GLA;D and at 6, 12 and 24 month follow-up.)
- Change in self-rated health using the Quality of Life questionnaire (EQ5D)(Change between baseline, 2 weeks post cryoneurolysis, post GLA;D and at 6, 12 and 24 month follow-up.)
- Change in the subscale "Function in daily living (ADL)" using the Knee injury and Osteoarthritis Score (KOOS score)(Change between baseline, 2 weeks post cryoneurolysis, post GLA;D and at 6, 12 and 24 month follow-up.)
- Change in use of Analgesics(Change between baseline, 2 weeks post cryoneurolysis, post GLA;D and at 6, 12 and 24 month follow-up.)
- Number of Adverse effects(Reported adverse effects 2 weeks post cryoneurolysis, post GLA;D and at 6, 12 and 24 month follow-up.)
- Change in Functional Performance Evaluated by the 9 step stair test.(Change between baseline, 2 weeks post cryoneurolysis, post GLA;D and at 6, 12 and 24 month follow-up.)
- Change in Quality of Life using the Quality of Life questionnaire (EQ5D)(Change between baseline, 2 weeks post cryoneurolysis, post GLA;D and at 6, 12 and 24 month follow-up.)
- Change in the subscale "Knee related Quality of Life (QoL)" using the Knee injury and Osteoarthritis Score (KOOS score)(Change between baseline, 2 weeks post cryoneurolysis, post GLA;D and at 6, 12 and 24 month follow-up.)
- Change in the subscale "Pain" using the Knee injury and Osteoarthritis Score (KOOS score)(Change between baseline, 2 weeks post cryoneurolysis, post GLA;D and at 6, 12 and 24 month follow-up.)
- Change in the subscale "other Symptoms" using the Knee injury and Osteoarthritis Score (KOOS score)(Change between baseline, 2 weeks post cryoneurolysis, post GLA;D and at 6, 12 and 24 month follow-up.)
- Change in the subscale "Function in sport and recreation (Sport/Rec)" using the Knee injury and Osteoarthritis Score (KOOS score)(Change between baseline, 2 weeks post cryoneurolysis, post GLA;D and at 6, 12 and 24 month follow-up.)
研究者
Niels-Peter Brøchner Nielsen, PhD
Post doc, Research employee
Esbjerg Hospital - University Hospital of Southern Denmark