Cryoanalgesia to Treat Phantom Limb Pain Following a Trans-Femoral (Above-Knee) Amputation: A Randomized, Sham-Controlled Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Average pain intensity change from baseline 1 month post-intervention
研究概览
简要总结
When a limb is severed, pain perceived in the part of the body that no longer exists often develops and is called "phantom limb" pain. Unfortunately, phantom pain goes away in only 16% of afflicted individuals, and there is currently no reliable definitive treatment. The exact reason that phantom limb pain occurs is unclear, but when a nerve is cut-as happens with an amputation-changes occur in the brain and spinal cord that actually increase with worsening phantom pain. These abnormal changes may often be corrected by putting local anesthetic-called a "nerve block"-on the injured nerve, effectively keeping any "bad signals" from reaching the brain with a simultaneous resolution of the phantom limb pain. However, when the nerve block resolves after a few hours, the phantom pain returns. But, this demonstrates that the brain abnormalities-and phantom pain-that occur with an amputation are not necessarily fixed, and may be dependent upon the "bad" signals being sent from the injured nerve(s), suggesting that a very long peripheral nerve block-lasting many months rather than hours-may permanently reverse the abnormal changes in the brain, and provide definitive relief from phantom pain. A prolonged nerve block lasting a few months may be provided by freezing the nerve using a process called "cryoneurolysis". The ultimate objective of the proposed research study is to determine if cryoanalgesia is an effective treatment for intractable post-amputation phantom limb pain. The proposed pilot study will include subjects with an existing above-knee amputation who experience intractable daily phantom limb pain. A single ultrasound-guided treatment of cryoneurolysis (or sham block-determined randomly like a flip of a coin) will be applied to the major nerves of the thigh. Although not required, each subject may return 4-6 months later for the alternative treatment (if the first treatment is sham, then the second treatment would be cryoneurolysis) so that all participants have the option of receiving the active treatment. Subjects will be followed for a total of 12 months with data collected by telephone.
详细描述
Subjects will be asked to make no changes to their analgesic regimen for at least 1 month prior to the cryoneurolysis procedure and continuing for 4 months until the measurement of the primary end point-for the duration of the study, all patients will be allowed to continue their pre-intervention analgesics. For individuals of childbearing potential, a sample of urine will be collected before any study interventions to confirm a non-pregnant state.
All subjects will have a peripheral intravenous catheter inserted, standard noninvasive monitors applied, and oxygen administered via a facemask or nasal cannula. Midazolam and/or fentanyl (IV) will be titrated for patient comfort.
Treatment group allocation (randomization). Participants will be allocated to one of two possible treatments groups:
- Cryoneurolysis
- Sham procedure (Control) Randomization lists will be created using computer-generated tables by the Investigational Pharmacy (UC San Diego) in a 1:1 ratio and block sizes of 2. Treatment group assignment will be conveyed to the investigators in the form of sealed, opaque envelopes only by the treating investigator. Therefore, all investigators and participants will be masked to treatment group assignment, with the only exception being the investigator and coordinator who perform the procedure (and will not have subsequent contact with the participant). This protocol will enable a randomized, observer- and participant-masked, sham/placebo-controlled study. It is impossible to mask the individual performing the cryoneurolysis procedure because the ice ball forming at the distal end of the probe-with active treatment-is clearly visible by ultrasound; and the lack of an ice ball for placebo participants is equally clear. It is essential to continuously visualize the probe and target nerve throughout the two freeze/thaw cycles to ensure the entire nerve diameter is adequately treated and remains relatively motionless. This cannot be achieved if the ultrasound is turned off during nitrous oxide administration to mask the provider; and the investigators prioritize patient safety over masking of the physician administering the intervention.
All participants will have a peripheral intravenous (IV) catheter inserted, standard noninvasive monitors applied (blood pressure cuff, pulse oximeter, 5-lead ECG), and oxygen administered via a nasal cannula or facemask. Midazolam and fentanyl (IV) will be titrated for patient comfort, while ensuring that patients remain responsive to verbal cues.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
All individuals will be masked to treatment with the exception of the anesthesiologist administering the procedure who will choose which probe to use: the functional or sham. Of note, this individual could not be masked to treatment since the cryoneurolysis ice ball is visualized on ultrasound; and, the practitioner would see a lack of ice ball formation for the sham probes.
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
- •Adult patients of at least 18 years of age
- •Trans-femoral traumatic or surgical amputation at least 12 weeks prior to enrollment distal to the hip (femoral head remaining)
- •Experiencing at least moderate phantom limb pain-defined as a 4 or higher on the Numeric Rating Scale (NRS; 0-10, 0= no pain; 10=worst imaginable pain)-at least daily for the previous 2 months
- •willing to avoid both changes to their analgesic regimen as well as elective surgical procedures from 1 month prior to and at least 4 months following the initial cryoneurolysis procedure.
排除标准
- •allergy to amide local anesthetics
- •incarceration
- •inability to communicate with the investigators
- •morbid obesity (body mass index > 40 kg/m2)
- •possessing any contraindication specific to cryoneurolysis such as a localized infection at the treatment site, cryoglobulinemia, cold urticaria and Reynaud's Syndrome
研究组 & 干预措施
Sham Comparator first, then optional cryoneurolysis treatment
Initial treatment: Sham cryoneurolysis of the major nerves of the thigh in the residual limb: The cryoneurolysis device will be triggered using 1 cycle of 5.5-minute argon activation followed by a 30-60 second defrost period with helium (Varian) or 2 cycles of 2-minute gas activation with a sham probe separated by a 30-60 second defrost (Epimed). However, for sham treatment, the gas is NOT deployed to the probe tip and therefore there is NO drop in temperature with NO resulting cryoneurolysis.
Active crossover treatment: Cryoneurolysis of the major nerves of the thigh in the residual limb: The cryoneurolysis device will be triggered using 1 cycle of 5.5-minute argon activation followed by a 30-60 second defrost period with helium (Varian) or 2 cycles of 2-minute gas activation with an active probe separated by a 30-60 second defrost (Epimed). For active treatment, the gas will be deployed to the probe tip where a drop in temperature will result in cryoneurolysis.
干预措施: SHAM cryoneurolysis (Device)
Sham Comparator first, then optional cryoneurolysis treatment
Initial treatment: Sham cryoneurolysis of the major nerves of the thigh in the residual limb: The cryoneurolysis device will be triggered using 1 cycle of 5.5-minute argon activation followed by a 30-60 second defrost period with helium (Varian) or 2 cycles of 2-minute gas activation with a sham probe separated by a 30-60 second defrost (Epimed). However, for sham treatment, the gas is NOT deployed to the probe tip and therefore there is NO drop in temperature with NO resulting cryoneurolysis.
Active crossover treatment: Cryoneurolysis of the major nerves of the thigh in the residual limb: The cryoneurolysis device will be triggered using 1 cycle of 5.5-minute argon activation followed by a 30-60 second defrost period with helium (Varian) or 2 cycles of 2-minute gas activation with an active probe separated by a 30-60 second defrost (Epimed). For active treatment, the gas will be deployed to the probe tip where a drop in temperature will result in cryoneurolysis.
干预措施: ACTIVE cryoneurolysis (Device)
结局指标
主要结局
Average pain intensity change from baseline 1 month post-intervention
时间窗: Baseline and Month 1
The "average" pain level measured using the numeric rating scale for the previous 24 hours. This is a 0-10 Likert scale measuring pain level with 0=no pain and 10=worst imaginable pain. The primary outcome will be the change from baseline in average pain intensity as measured with the numeric rating scale 1 month following the initial intervention.
次要结局
- CROSSOVER Least Daily Residual Pain intensity change from baseline(Following the CROSSOVER treatment on Days 1 and 7; Months 1, 2, 3, and 4)
- Current Daily Phantom Pain intensity change from baseline(Post-intervention days 1, 7, and Months 1, 2, 3, 4, and 12)
- CROSSOVER Average Daily Phantom Pain intensity change from baseline(Following the CROSSOVER treatment on Days 1 and 7; Months 1, 2, 3, and 4)
- Current Residual Limb Pain intensity change from baseline(Post-intervention days 1, 7, and Months 1, 2, 3, 4, and 12)
- Least Daily Phantom Pain intensity change from baseline(Post-intervention days 1, 7, and Months 1, 2, 3, 4, and 12)
- Non-painful phantom sensations Frequency, initial intervention(Post-intervention days 1, 7, and Months 1, 2, 3, 4, and 12)
- CROSSOVER Worst Phantom Pain intensity change from baseline(Following the CROSSOVER treatment on Days 1 and 7; Months 1, 2, 3, and 4)
- CROSSOVER Average Daily Residual Pain intensity change from baseline(Following the CROSSOVER treatment on Days 1 and 7; Months 1, 2, 3, and 4)
- CROSSOVER Current Residual Pain intensity change from baseline(Following the CROSSOVER treatment on Days 1 and 7; Months 1, 2, 3, and 4)
- Brief Pain Inventory (interference sub scale), initial intervention(Post-intervention days 1, 7, and Months 1, 2, 3, 4, and 12)
- Residual Limb Pain Duration, CROSSOVER intervention(Following the CROSSOVER treatment on Days 1 and 7; Months 1, 2, 3, and 4)
- Average Daily Phantom Pain intensity change from baseline(Post-intervention days 1, 7, and Months 2, 3, 4, and 12)
- Worst Daily Phantom Pain intensity change from baseline(Post-intervention days 1, 7, and Months 1, 2, 3, 4, and 12)
- CROSSOVER Least Phantom Pain intensity change from baseline(Following the CROSSOVER treatment on Days 1 and 7; Months 1, 2, 3, and 4)
- Average Daily Residual Limb Pain intensity change from baseline(Post-intervention days 1, 7, and Months 1, 2, 3, 4, and 12)
- Worst Daily Residual Limb Pain intensity change from baseline(Post-intervention days 1, 7, and Months 1, 2, 3, 4, and 12)
- Patient Global Impression of Change, Initial intervention(Post-intervention days 1, 7, and Months 1, 2, 3, 4, and 12)
- Phantom Limb Pain Frequency, initial intervention(Post-intervention days 1, 7, and Months 1, 2, 3, 4, and 12)
- Residual Limb Pain Duration, initial intervention(Post-intervention days 1, 7, and Months 1, 2, 3, 4, and 12)
- CROSSOVER Current Phantom Pain intensity change from baseline(Following the CROSSOVER treatment on Days 1 and 7; Months 1, 2, 3, and 4)
- Least Daily Residual Limb Pain intensity change from baseline(Post-intervention days 1, 7, and Months 1, 2, 3, 4, and 12)
- Phantom Limb Pain Duration, initial intervention(Post-intervention days 1, 7, and Months 1, 2, 3, 4, and 12)
- CROSSOVER Worst Daily Residual Pain intensity change from baseline(Following the CROSSOVER treatment on Days 1 and 7; Months 1, 2, 3, and 4)
- Residual Limb Pain Frequency, initial intervention(Post-intervention days 1, 7, and Months 1, 2, 3, 4, and 12)
- Non-painful phantom sensations Duration, initial intervention(Post-intervention days 1, 7, and Months 1, 2, 3, 4, and 12)
- Phantom Limb Pain Frequency, CROSSOVER intervention(Following the CROSSOVER treatment on Days 1 and 7; Months 1, 2, 3, and 4)
- Residual Limb Pain Frequency, CROSSOVER intervention(Following the CROSSOVER treatment on Days 1 and 7; Months 1, 2, 3, and 4)
- Non-painful phantom sensations Duration, CROSSOVER intervention(Following the CROSSOVER treatment on Days 1 and 7; Months 1, 2, 3, and 4)
- CROSSOVER Brief Pain Inventory (interference sub scale)(Following the CROSSOVER treatment on Days 1 and 7; Months 1, 2, 3, and 4)
- Phantom Limb Pain Duration, CROSSOVER intervention(Following the CROSSOVER treatment on Days 1 and 7; Months 1, 2, 3, and 4)
- Non-painful phantom sensations Frequency, CROSSOVER intervention(Following the CROSSOVER treatment on Days 1 and 7; Months 1, 2, 3, and 4)
- CROSSOVER Patient Global Impression of Change(Following the CROSSOVER treatment on Days 1 and 7; Months 1, 2, 3, and 4)
研究者
Brian M. Ilfeld, MD, MS
Professor of Anesthesiology
University of California, San Diego