Regional Anesthesia and Valproate Sodium for the Prevention of Chronic Post-Amputation Pain
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 128
- 试验地点
- 2
- 主要终点
- Number of Patients With Chronic Post-amputation Pain
研究概览
简要总结
The objectives of this study are, to test the effectiveness of Valproic Acid (VPA) in the prevention of chronic neuropathic and post-amputation pain, as well as to further define the underlying inflammatory and epigenetic mechanisms that lead to the development of such chronic pain.
HYPOTHESES AND QUESTIONS
Hypothesis 1: The use of oral valproic acid in combination with regional anesthesia in surgical limb-injury patients will decrease the incidence of chronic nerve injury and post-amputation pain.
Goal 1: In a blinded, randomized placebo-controlled, multi-center clinical trial, investigators will determine if oral VPA added to regional anesthesia and standard perioperative management will reduce the incidence of nerve injury and post-amputation pain when compared with regional anesthesia alone.
Hypothesis 2: The transition from acute to chronic pain is mediated via epigenetic mechanisms (differential DNA methylation) in genes involved in nociception.
Goal 2: Investigators will analyze the DNA methylation patterns of patients with different types of neuropathic and post-amputation pain and determine if they are altered by VPA.
详细描述
RESEARCH DESIGN
This study will be a prospective, randomized, double-blinded, placebo-controlled trial to test the efficacy of valproic acid (VPA) in reducing the incidence of chronic neuropathic and post-amputation pain following amputation, stump revision, and surgery for limb injury with neurologic damage. Patients randomized to the "Control arm" of the trial, will receive standard regional anesthesia catheters (either peripheral nerve or epidural catheter), anesthetic management and a placebo. Patients randomized to the "Intervention arm" of the trial will receive standard regional anesthesia catheters (either peripheral nerve or epidural catheter), anesthetic management, and valproic acid 250mg preoperatively, and then three times per day for either 6 days post-operatively or until the time of discharge.
METHODOLOGY
The enrollment goal for the study (from all sites) will be 224 patients. Subjects will be recruited from the surgical clinics and the anesthesia pre-operative clinic. Outcomes for patients in the intervention arm will be compared with those managed with the current institutional standards of care including regional anesthesia catheter infusions. The study team anticipates a 10% drop-out rate at 3 months secondary to death and loss to follow up. Thus 202 evaluable patients (101 patients in each arm) at 3 months after surgery will be included in this study.
After screening and enrollment, the study medication (VPA or placebo) will be administered. Research blood samples will be collected preoperatively, postoperatively (at the completion of study drug administration, and at the Amputation Clinic follow-up for expression analysis. The third and final blood draw will be taken at the 3 month follow up. If patient is unavailable the research team will make accommodations to collect blood sample at the 6 month follow up or at a time of maximal patient convenience, not to exceed 18 months from study enrollment. All samples will be de-identified and subsequently studied in our laboratory and core facilities at Duke. Study specific questionnaires will be administered during the hospital stay, at 1 month (via mail), at 3 months (in clinic) and at 6 months (in clinic when possible).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 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
- •Male and female active duty military personnel or veterans, age 18 years and older.
- •Patient is scheduled to undergo amputation, stump revision, or surgery for a limb injury with neurologic damage.
- •Patient able to provide written informed consent prior to any study procedures.
排除标准
- •Severe Traumatic Brain Injury (Diagnosis of traumatic brain injury resulting in documented, permanent or prolonged cognitive deficits that would preclude participation in the study)
- •Significant cognitive deficits or dementia of any cause as noted in Computerized Patient Record System(CPRS).
- •Patient has a designated Legally Authorized Representative
- •Substantial hearing loss without alternative means of communication.
- •Patient has documented spinal cord injury with permanent or persistent deficits
- •Patient is under age 18 or a legal Minor
- •Current pregnancy or lactation
- •Cirrhosis with evidence of decompensation: coagulopathy International Normalized Ratio (INR) >1.3, thrombocytopenia with platelets <100,000, ascites or hepatic encephalopathy
- •Therapy with valproic acid or other valproates, coumadin, chlorpromazine and olanzapine at the time of surgery and study drug administration
- •Current diagnosis of seizure disorder requiring anti-epileptic medication
- •Current therapy with tricyclic antidepressants (eg: amitriptyline, nortriptyline, imipramine, desipramine) at doses greater than 50mg/day
- •Currently taking zidovudine
- •Current diagnosis of malaria requiring anti-malaria medication (such as mefloquine and chloroquine)
- •Currently taking monoamine oxide inhibitors (MAOI)
- •Allergy to valproates or valproic acid
- •Contraindication to, or refusal of, regional anesthesia catheter
- •BMI > 50
研究组 & 干预措施
Cherry syrup
Cherry Syrup: Patients randomized to the "Control arm" of the trial will receive standard regional anesthesia catheters (either peripheral nerve or epidural catheter), anesthetic management and the placebo.
干预措施: Cherry Syrup (Other)
Valproic Acid
"Intervention arm" patients will receive standard regional anesthesia catheters (either peripheral nerve or epidural catheter), anesthetic management, and valproic acid.
干预措施: Valproic Acid (Drug)
结局指标
主要结局
Number of Patients With Chronic Post-amputation Pain
时间窗: 3 months or time of final adjudication assessment, up to 6 months
The primary endpoint is the incidence of chronic pain after surgery. The study team will use the average pain score over the past week as noted on the Self-Reported Leeds Assessment of Neuropathic Symptoms and Signs pain scale (S-LANSS) for the assessment of pain, and define chronic pain as a score greater than or equal to 3.
次要结局
- Incidence of Pain Sub-types(Assessments at enrollment and 3 months or time of final adjudication assessment (up to 6 months))
- Effect on Analgesic Requirement(Assessments during hospitalization (0-24 hours and 24-48 hours post-surgery))
- Brief Pain Inventory (BPI) Short Form Score(Assessments at enrollment and 3 months or time of final adjudication assessment (up to 6 months))
- Change in Self-Reported Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale (S-LANSS)(Assessments at enrollment and 3 months or time of final adjudication assessment (up to 6 months))
- Defense and Veterans Pain Rating Scale (DVPRS) Score(Assessments at enrollment and 3 months or time of final adjudication assessment (up to 6 months))
- Richmond Agitation-Sedation Scale (RASS)(during hospitalization (0-24 hours and 24-48 hours post-surgery))