Study to Identify the Genetic Variations Associated With Phantom Limb Pain

• Conditions: Phantom Limb
• Interventions: Procedure: Blood Draw

• Registration Number: NCT01462448
• Lead Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine

Brief Summary

The purpose of this study is to determine if there is a genetic component to phantom limb pain. DNA will be analyzed for single nucleotide polymorphisms (SNPs) between the control and phantom limb pain group. Total RNA will also be isolated and profiled to asses the degree to which our gene(s) of interest are expressed in the presence or absence of phantom limb pain. Some proteins, such as inflammatory antibodies or the neurotrophin brain-derived neurotrophic factor (BDNF), will also be assessed for their association(s) with phantom limb pain.

Detailed Description

Most patients (90-95%)with major limb amputations experience a phantom limb--the vivid impression that the limb is still present. In many cases, the sensation is painful for reasons that are currently not well understood. A small subset of amputees (\<10%) never experience phantom limb pain (PLP), the painful sensation felt in the amputated limb. This difference suggests that there may be a genetic component that precludes some patients from ever experiencing PLP. Understanding the genetic components of PLP may help in predicting which patients will experience PLP and which amputees will respond to the various treatment options available.

In order to understand the genetic aspects and ultimately develop more effective treatment options in the future, patients with and without PLP will be asked to give 30 mls of blood after overnight fasting. These blood samples will be de-identified and sent to the National Institutes of Health (NIH) in Bethesda, Maryland, where all of the genetic analyses will take place.

Study Timeline

• Study First Submitted: 2011-10-24
• Study First Submitted QC: 2011-10-27
• Study First Posted: 2011-10-31
• Study Start: 2012-03
• Primary Completion: 2014-04
• Status Verified: 2019-04
• Last Update Submitted: 2019-04-09
• Last Update Posted: 2019-04-10
• Study Completion: 2019-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 726

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
No Phantom Limb Pain	Blood Draw	Subjects in the group will have a lower or upper extremity amputation(s) without the presence of phantom limb sensation.
Phantom Limb Pain	Blood Draw	Subjects will have lower or upper extremity amputation(s) that have resulted in the presence of phantom limb pain.

Primary Outcome Measures

Name	Time	Method
Identification of Unique Single Nucleotides Polymorphisms (SNPs) associated with Phantom Limb Pain (PLP)	5 years	The primary outcome measure for this study is the identification of unique SNPs that may correlate with PLP. Patients will undergo a one-time blood draw and fill out a survey characterizing their phantom limb pain. The PLP characteristics along with DNA analysis using Affymetrix SNP chip technology will be used to match genotype with phenotype.

Secondary Outcome Measures

Name	Time	Method
Correlation between Phantom Limb Pain (PLP) and Blood Levels of Antibodies Associated with Peripheral Nerve Damage	5 years	The underlying hypothesis of the secondary outcome measure is that damage to peripheral nerves provokes a humoral immune response to neuronal and glial proteins that can be detected by measuring specific antibodies in blood. The data obtained will lead to a more complete understanding of pathogenic mechanisms in PLP and potential biomarkers for sub-classification, prognosis, and intervention.
Correlation between Phantom Limb Pain (PLP) and Serum Levels of Brain-derived Neurotrophic Factor (BDNF)	5 years	BDNF has been implicated in pain nociception and is therefore pertinent to our study of phantom limb pain. After peripheral nerve injury, BDNF expression is dramatically increased in pain receptors of the brainstem.
Correlation between Phantom Limb Pain (PLP) and Unique Transcribed RNA	5 years	Many underlying causes for neuropathic pain involve changes in messenger ribonucleic acid (mRNA) levels because of altered gene expression or transcript stability. The study will isolate total RNA from blood and measure the relative amounts of transcribed RNA under the condition of phantom limb pain or no phantom limb pain.

Trial Locations

Locations (1)

Walter Reed National Military Medical Center (WRNMMC); 🇺🇸 Bethesda, Maryland, United States