Valproic Acid for the Prevention of Post-Amputation Pain
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|ClinicalTrials.gov Identifier: NCT01928849|
Recruitment Status : Completed
First Posted : August 27, 2013
Results First Posted : October 25, 2018
Last Update Posted : December 19, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Pain, Phantom Pain, Neuropathic||Drug: Valproic Acid Other: Cherry Syrup||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||128 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Regional Anesthesia and Valproate Sodium for the Prevention of Chronic Post-Amputation Pain|
|Study Start Date :||December 2013|
|Actual Primary Completion Date :||September 26, 2017|
|Actual Study Completion Date :||September 26, 2017|
Placebo Comparator: 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.
Other: Cherry Syrup
Intervention arm patients 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 6 days post-operatively.
Experimental: Valproic Acid
"Intervention arm" patients will receive standard regional anesthesia catheters (either peripheral nerve or epidural catheter), anesthetic management, and valproic acid.
Drug: Valproic Acid
"Intervention" patients will receive standard regional anesthesia catheters (either peripheral nerve or epidural catheter), anesthetic management and oral valproic acid 250mg preoperatively, then three times per day for either 6 days post-operatively or until discharge from the hospital.
Other Name: Depacon, Depakene, Depakote, Stavzor
- Number of Patients With Chronic Post-amputation Pain [ Time Frame: 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.
- Incidence of Pain Sub-types [ Time Frame: Assessments at enrollment and 3 months or time of final adjudication assessment (up to 6 months) ]The incidence of neuropathic limb or post-amputation pain sub-types as defined by adjudication classification at each assessment time point.
- Effect on Analgesic Requirement [ Time Frame: Assessments during hospitalization (0-24 hours and 24-48 hours post-surgery) ]The effect of study drug on perioperative analgesic consumption and corresponding analysis of pain/sedation scales. Outcome defined as total opioid consumption (mg) during each 24-hour periods following surgery.
- Brief Pain Inventory (BPI) Short Form Score [ Time Frame: Assessments at enrollment and 3 months or time of final adjudication assessment (up to 6 months) ]The BPI short form is a multidimensional patient-completed measure that assesses the sensory component of pain intensity. We will analyze the change in average pain score question (ranges 0-10) and the sum of the 7 interference questions (total range 0-70) from baseline. Higher score indicates greater pain and interference.
- Change in Self-Reported Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale (S-LANSS) [ Time Frame: Assessments at enrollment and 3 months or time of final adjudication assessment (up to 6 months) ]The S-LANSS is a self-reported version of the Leeds Assessment of Neuropathic Symptoms and Signs pain scale. It aims to differentiate neuropathic pain from somatic or nociceptive pain. We will analyze the change in numeric average pain score during the past week (range from 0-10) from baseline. Higher scores indicate greater pain.
- Defense and Veterans Pain Rating Scale (DVPRS) Score [ Time Frame: Assessments at enrollment and 3 months or time of final adjudication assessment (up to 6 months) ]The DVPRS is a pain assessment tool developed by the military in an effort to improve reliability and interpretability of pain assessment in the military population. It has been found to be an effective and valid tool in this population. We will analyze the change in numeric pain response (range 0-10) and the sum of the four supplemental questions (range 0-40) from baseline. Higher scores indicate greater pain and functional limitations.
- Richmond Agitation-Sedation Scale (RASS) [ Time Frame: during hospitalization (0-24 hours and 24-48 hours post-surgery) ]The RASS is a commonly used, valid and reliable assessment tool for use in hospitalized patients. Validity testing reveals good inter-rater reliability among medical, surgical, and intensive care units. We will analyze the numeric score at each assessment (range -5 (unarousable) to 4 (combative)).
- Observation of Epigenetic Alterations That Occur in the Transition From Acute to Chronic Pain. [ Time Frame: Changes between enrollment, end of study drug and 3 months or time of final adjudication ]Epigenetic analysis (DNA methylation) will be correlated with pain sub-type and use of Valproic Acid.
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): NCT01928849
|United States, Maryland|
|Walter Reed National Military Medical Center|
|Bethesda, Maryland, United States, 20814|
|United States, North Carolina|
|Duham VA Medical Center|
|Durham, North Carolina, United States, 27705|
|Principal Investigator:||Thomas E Buchheit, MD||Duke University|