Study to Identify the Genetic Variations Associated With Phantom Limb Pain

August 7, 2025 updated by: Henry M. Jackson Foundation for the Advancement of Military Medicine
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
726

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20889
        • Walter Reed National Military Medical Center (WRNMMC)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

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.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
Other Names:
  • 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
Other Names:
  • Venipuncture

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Identification of Unique Single Nucleotides Polymorphisms (SNPs) associated with Phantom Limb Pain (PLP)
Time Frame: 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.
5 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Correlation between Phantom Limb Pain (PLP) and Blood Levels of Antibodies Associated with Peripheral Nerve Damage
Time Frame: 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.
5 years
Correlation between Phantom Limb Pain (PLP) and Serum Levels of Brain-derived Neurotrophic Factor (BDNF)
Time Frame: 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.
5 years
Correlation between Phantom Limb Pain (PLP) and Unique Transcribed RNA
Time Frame: 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.
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Henry M. Jackson Foundation for the Advancement of Military Medicine

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Uniformed Services University of the Health Sciences

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Paul F. Pasquina, MD, MC, Walter Reed National Military Medical Center (WRNMMC)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 6, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 24, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 27, 2011

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 31, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 12, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 7, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 20429
  • HU0001-11-1-0005 (Other Grant/Funding Number: Uniformed Services University of Health Sciences (USUHS))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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