Study to Identify the Genetic Variations Associated With Phantom Limb Pain

Phantom Limb Clinical Trial

Official title:

Study to Identify the Genetic Variations Associated With Phantom Limb Pain

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01462448
• Other study ID #: 20429
• Secondary ID: HU0001-11-1-0005
• Status: Active, not recruiting
• Start date: March 2012
• Est. completion date: August 2019

Study information

• Verified date: April 2019
• Source: Henry M. Jackson Foundation for the Advancement of Military Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 726
• Est. completion date: August 2019
• Est. primary completion date: April 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Chronic PLP Group:

• At least 18 years of age.

• Written informed consent and written authorization for use or release of health and research study information

• Single or multiple upper and/or lower limb amputation

• At least three months post-amputation

• Ability to follow study instructions and likely to complete required visit(s)

• Experienced PLP for at least one month and at least 3 times per week

• Phantom limb pain differentiated from residual limb pain by physical exam.

• Subjects taking blood thinners or other medications that do not increase risk during a blood draw.

Non-Chronic PLP Group:

• At least 18 years of age.

• Written informed consent and written authorization for use or release of health and research study information

• Single or multiple upper and/or lower limb(s) amputation

• At least three months post-amputation

• Ability to follow study instructions and likely to complete required visit(s)

• Experienced PLP less than 10 times total and/or for less than two weeks

• Subjects taking blood thinners or other medications that do not increase risk during a blood draw.

Related Conditions & MeSH terms

• Phantom Limb

Intervention

Procedure:
• Blood Draw
Single blood draw of 30 ml

Locations

Country	Name	City	State
United States	Walter Reed National Military Medical Center (WRNMMC)	Bethesda	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Henry M. Jackson Foundation for the Advancement of Military Medicine	Uniformed Services University of the Health Sciences

Country where clinical trial is conducted

United States, 

References & Publications (6)

Jensen TS, Krebs B, Nielsen J, Rasmussen P. Phantom limb, phantom pain and stump pain in amputees during the first 6 months following limb amputation. Pain. 1983 Nov;17(3):243-56. — View Citation

Katz J, Melzack R. Pain 'memories' in phantom limbs: review and clinical observations. Pain. 1990 Dec;43(3):319-36. Review. — View Citation

Kooijman CM, Dijkstra PU, Geertzen JH, Elzinga A, van der Schans CP. Phantom pain and phantom sensations in upper limb amputees: an epidemiological study. Pain. 2000 Jul;87(1):33-41. — View Citation

Montoya P, Larbig W, Grulke N, Flor H, Taub E, Birbaumer N. The relationship of phantom limb pain to other phantom limb phenomena in upper extremity amputees. Pain. 1997 Aug;72(1-2):87-93. — View Citation

Ramachandran VS, Hirstein W. The perception of phantom limbs. The D. O. Hebb lecture. Brain. 1998 Sep;121 ( Pt 9):1603-30. Review. — View Citation

Sherman RA, Sherman CJ, Parker L. Chronic phantom and stump pain among American veterans: results of a survey. Pain. 1984 Jan;18(1):83-95. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of Unique Single Nucleotides Polymorphisms (SNPs) associated with Phantom Limb Pain (PLP)	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.	5 years
Secondary	Correlation between Phantom Limb Pain (PLP) and Blood Levels of Antibodies Associated with Peripheral Nerve Damage	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.	5 years
Secondary	Correlation between Phantom Limb Pain (PLP) and Serum Levels of Brain-derived Neurotrophic Factor (BDNF)	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.	5 years
Secondary	Correlation between Phantom Limb Pain (PLP) and Unique Transcribed RNA	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.	5 years