Study to Identify the Genetic Variations Associated With Phantom Limb Pain

This study is currently recruiting participants.
Verified September 2013 by Henry M. Jackson Foundation for the Advancement of Military Medicine
Sponsor:
Collaborator:
Uniformed Services University of the Health Sciences
Information provided by (Responsible Party):
Henry M. Jackson Foundation for the Advancement of Military Medicine
ClinicalTrials.gov Identifier:
NCT01462448
First received: October 24, 2011
Last updated: September 3, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention
Phantom Limb
Procedure: Blood Draw

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Study to Identify the Genetic Variations Associated With Phantom Limb Pain

Further study details as provided by Henry M. Jackson Foundation for the Advancement of Military Medicine:

Primary Outcome Measures:
  • Identification of Unique Single Nucleotides Polymorphisms (SNPs) associated with Phantom Limb Pain (PLP) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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:
  • Correlation between Phantom Limb Pain (PLP) and Blood Levels of Antibodies Associated with Peripheral Nerve Damage [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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.


Biospecimen Retention:   Samples With DNA

Whole blood, serum


Estimated Enrollment: 1000
Study Start Date: March 2012
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Phantom Limb Pain
Subjects will have lower or upper extremity amputation(s) that have resulted in the presence of phantom limb pain.
Procedure: Blood Draw
Single blood draw of 30 ml after a period of overnight fasting
Other Name: Venipuncture
No Phantom Limb Pain
Subjects in the group will have a lower or upper extremity amputation(s) without the presence of phantom limb sensation.
Procedure: Blood Draw
Single blood draw of 30 ml after a period of overnight fasting
Other Name: Venipuncture

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Subjects to be recruited at WRNMMC will be military health care beneficiaries age 18 and older who have sustained one or more amputations. To minimize within group genetic variability, the study focuses on European American populations only.

Criteria

Inclusion Criteria:

  • Chronic Phantom Limb Pain Group:

    • European American subjects, at least 18 years of age
    • Written informed consent and written authorization for use or release of health research study information
    • Single or multiple upper and/or lower limb amputation
    • Ability to follow study instructions and likely to complete required visit
    • Experience phantom limb pain for at least one month and at least 3 times per week
    • Phantom limb pain differentiated from residual limb pain by physical exam
  • Non-chronic Phantom Limb Pain Group:

    • European American subjects, at least 18 years of age
    • Written informed consent and written authorization for use or release of health research study information
    • Single or multiple upper and/or lower limb amputation
    • Ability to follow study instructions and likely to complete required visit
    • Experience phantom limb pain less than 10 times total and/or for less than two weeks
    • Phantom limb pain differentiated from residual limb pain by physical exam

Exclusion Criteria:

  • Chronic Phantom Limb Pain Group:

    • Age less than 18
    • Non-European American descent
    • Less than three months lapsed since amputation
    • Known uncontrolled systemic disease- known cancer not in remission, known on-going infection, lupus, kidney disease requiring dialysis, any other systemic disease which might affect ability to participate in this study's blood draw
    • Any condition or situation that, in the investigator's opinion, may put the subject at significant risk or confound study results
    • Experience phantom limb pain for less than one month or less than 3 times/week
    • Hemophilia or other chronic disease or medication regimen that would make a blood draw dangerous or inadvisable for the subject as determined by querying the subject
  • Non-chronic Phantom Limb Pain Group:

    • Age less than 18
    • Non-European American descent
    • Less than three months lapsed since amputation
    • Known uncontrolled systemic disease- known cancer not in remission, known on-going infection, lupus, kidney disease requiring dialysis, any other systemic disease which might affect ability to participate in this study's blood draw
    • Any condition or situation that, in the investigator's opinion, may put the subject at significant risk or confound study results
    • Experience phantom limb pain for less than one month or less than 3 times/week
    • Hemophilia or other chronic disease or medication regimen that would make a blood draw dangerous or inadvisable for the subject as determined by querying the subject
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01462448

Contacts
Contact: Monica L. Tung, BA 301-295-8920 monica.l.tung.ctr@health.mil
Contact: Briana N. Perry, BA 240-204-1573 briana.n.perry.ctr@health.mil

Locations
United States, California
Naval Medical Center Recruiting
San Diego, California, United States, 92134
Contact: Carol Anne Drastal, CRN    619-532-7490    carol.drastal.ctr@med.navy.mil   
Principal Investigator: Stephen Hanling, MD         
United States, Maryland
Walter Reed National Military Medical Center (WRNMMC) Recruiting
Bethesda, Maryland, United States, 20889
Principal Investigator: Paul F. Pasquina, MD, MC         
Sub-Investigator: Monica L. Tung, BA         
Sub-Investigator: Briana N. Perry, BA         
Sponsors and Collaborators
Henry M. Jackson Foundation for the Advancement of Military Medicine
Uniformed Services University of the Health Sciences
Investigators
Principal Investigator: Paul F. Pasquina, MC, MD Walter Reed National Military Medical Center (WRNMMC)
  More Information

Publications:
Responsible Party: Henry M. Jackson Foundation for the Advancement of Military Medicine
ClinicalTrials.gov Identifier: NCT01462448     History of Changes
Other Study ID Numbers: 20429, HU0001-11-1-0005
Study First Received: October 24, 2011
Last Updated: September 3, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Henry M. Jackson Foundation for the Advancement of Military Medicine:
Phantom Limb
Genetic Variation
DNA Sequence Analysis
Amputation, Traumatic
Single Nucleotide Polymorphism
Visual Analog Pain Scale
Brain-Derived Neurotrophic Factor
Inflammatory Antibody
Peripheral Nerve Damage

Additional relevant MeSH terms:
Phantom Limb
Perceptual Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on April 15, 2014