Valproic Acid for the Prevention of Post-Amputation Pain
Condition: Pain, Phantom; Pain, Neuropathic
MeSH terms: Neuralgia; Phantom Limb
Intervention: Valproic Acid; Cherry Syrup
Intervention description: "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.; 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.
Intervention MeSH terms: Valproic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 128.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Amputation; Post-amputation Pain; Neuropathic pain; Valproic Acid; Anesthesia, Conduction; Neuralgia, stump

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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