Valproic Acid for the Prevention of Post-Amputation Pain
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.
Drug: Valproic Acid
Other: Cherry Syrup
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||Regional Anesthesia and Valproate Sodium for the Prevention of Chronic Post-Amputation Pain|
- Efficacy of Valproic Acid in reducing the Incidence of chronic neuropathic and post-amputation pain. [ Time Frame: 3 month assessment ] [ Designated as safety issue: Yes ]The primary endpoint is the incidence of chronic pain 3 months 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.
- Neuropathic limb or post-amputation pain, and the incidence of pain sub-types [ Time Frame: Assessments at enrollment, during hospitalization, as well as 1, 3 and 6 months post-surgery ] [ Designated as safety issue: No ]The incidence of neuropathic limb or post-amputation pain sub-types at the time points of 1, 3, and 6 months after surgery.
- Effect on analgesic requirement [ Time Frame: Assessments at enrollment, during hospitalization, as well as 1, 3 and 6 months post-surgery ] [ Designated as safety issue: Yes ]The effect of study drug on perioperative analgesic use and corresponding analysis of pain/sedation scales.
- Qualitative characterization of pain sub-types [ Time Frame: Assessment at 3 months post-surgery ] [ Designated as safety issue: No ]Qualitative characterization of neuropathic limb and post-amputation pain sub-types.
- Observation of epigenetic alterations that occur in the transition from acute to chronic pain. [ Time Frame: 3 months through to end of study, approximately 4 years ] [ Designated as safety issue: No ]Epigenetic analysis (DNA methylation) will be correlated with pain sub-type and use of Valproic Acid.
|Study Start Date:||December 2013|
|Estimated Study Completion Date:||September 2017|
|Estimated Primary Completion Date:||April 2017 (Final data collection date for primary outcome measure)|
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|
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
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|Contact: Dionne R Apedjihoun, MS||919-286-0411 ext 7372|
|Contact: Mary M Kirkleyemail@example.com|
|United States, Maryland|
|Walter Reed National Military Medical Center||Not yet recruiting|
|Bethesda, Maryland, United States, 20814|
|Contact: Mary McDuffie, RN 301-816-4722 firstname.lastname@example.org|
|Principal Investigator: Chester T Buckenmaier III, MD|
|Sub-Investigator: Lisa L Bleckner, MD|
|United States, North Carolina|
|Duham VA Medical Center||Recruiting|
|Durham, North Carolina, United States, 27705|
|Contact: Dionne R Apedjihoun, MS 919-286-0411 ext 7372 email@example.com|
|Contact: Mary M Kirkley 919-681-1170 Mary.firstname.lastname@example.org|
|Principal Investigator: Thomas E Buchheit, MD|
|Sub-Investigator: Andrew D Shaw, MD|
|Sub-Investigator: Thomas Van de Ven, MD|
|Sub-Investigator: Juliann Hobbs, MD|
|Sub-Investigator: Karthik Raghunathan, MD|
|Sub-Investigator: Srinivas Pyati, MD|
|Sub-Investigator: Cynthia K Shortell, MD|
|Principal Investigator:||Thomas E Buchheit, MD||Duke University|