Phase 2
N=128
Valproic Acid for the Prevention of Post-Amputation Pain
Pain, Phantom · Pain, Neuropathic
Bottom Line
View on ClinicalTrials.gov: NCT01928849 ↗Enrolled (actual)
128
Serious AEs
35.9%
Results posted
Oct 2018
Primary outcome: Primary: Number of Patients With Chronic Post-amputation Pain — 37; 36 Participants — p=0.53
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Valproic Acid (Drug); Cherry Syrup (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Duke University
- Primary completion
- Sep 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Patients With Chronic Post-amputation Pain |
37; 36 | 0.53 |
| SECONDARY Incidence of Pain Sub-types |
29; 31; 22; 26 | 0.95 |
| SECONDARY Effect on Analgesic Requirement |
59; 33; 49; 45 | 0.27 |
| SECONDARY Brief Pain Inventory (BPI) Short Form Score |
-2; -1; -15; -7 | 0.59 |
| SECONDARY Change in Self-Reported Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale (S-LANSS) |
-2; -2 | 0.35 |
| SECONDARY Defense and Veterans Pain Rating Scale (DVPRS) Score |
-2; 0; -9; -4.5 | 0.42 |
| SECONDARY Richmond Agitation-Sedation Scale (RASS) |
0; 0; 0; 0 | 0.27 |
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 50
Data sourced from ClinicalTrials.gov (NCT01928849). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.