Valproic Acid for the Prevention of Post-Amputation Pain

• Status: Completed
• Trial end date: 2017-09-26
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Duke University
• Collaborator: United States Department of Defense
• Treatments: Anesthetics; Valproic Acid

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