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.
|Pain, Phantom Pain, Neuropathic||Drug: Valproic Acid Other: Cherry Syrup||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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 ]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 ]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 ]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 ]Qualitative characterization of neuropathic limb and post-amputation pain sub-types.
- Brief Pain Inventory (BPI) short form [ Time Frame: baseline and 3 months ]The BPI short form is a multidimensional patient-completed measure that assesses the sensory component of pain intensity
- Self-Reported Leeds Assessment of Neuropathic Symptoms and Signs pain scale (S-LANSS) [ Time Frame: baseline and 3 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
- Defense and Veterans Pain Rating Scale (DVPRS) [ Time Frame: baseline and 3 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.
- Richmond Agitation-Sedation Scale (RASS) [ Time Frame: baseline and 3 months ]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.
- 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 ]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:||September 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
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
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01928849
|Contact: Rachel Moralesfirstname.lastname@example.org|
|United States, Maryland|
|Walter Reed National Military Medical Center||Recruiting|
|Bethesda, Maryland, United States, 20814|
|Contact: Mary McDuffie, RN 301-816-4722 email@example.com|
|Principal Investigator: Chester T Buckenmaier III, MD|
|United States, North Carolina|
|Duham VA Medical Center||Recruiting|
|Durham, North Carolina, United States, 27705|
|Contact: Rachel Morales 919-684-7229 firstname.lastname@example.org|
|Principal Investigator: Thomas E Buchheit, 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|
|Sub-Investigator: Hung Lun John Hsia, MD|
|Principal Investigator:||Thomas E Buchheit, MD||Duke University|