Pain after amputation
Conditions
Interventions
None listed
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: A total of twelve hundred (1200) subjects with upper or lower extremity amputations of any level will be enrolled in this study. Nine hundred fifty (950) subjects will have a history of phantom limb pain (PLP) and 250 will have no history of PLP.
Exclusion criteria
Exclusion criteria: Chronic PLP Group: * Subjects under age 18. * 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 the study results * Experienced PLP 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 PLP Group: * Subjects under age 18. * 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 the study results
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary goals of this study are to: i. Identify genetic variations responsible for PLP across the whole genome More than 90% of SNPs are found in introns or intergenic regions and most of them are probably of little functional consequence. However, SNPs in promoter regions can alter the affinity of DNA binding proteins and modify the level of gene expression. Other SNPs in exon / intron boundaries result in intron retention or exon skipping, thus profoundly changing the structure of the resulting protein. It is also possible that any genomic region where the SNP is located can function as an RNA interference element. The existence of SNPs in any portion of genomic DNA can be meaningful for the phenotype because of the complicated dynamics of DNA structure and gene expression. Genome wide association study along with multi-layer designed follow up study has been applied to clinical pain research. The advantage of this approach is that no specific functional genetic hypotheses are required prior to undertaking analysis. ii. Identify the gene expression profiles between individuals with and without PLP using microarray technology. It is suggested that analyzing gene expression profile will have clinical applications to neurological diseases in humans. Recently published studies have shown that there are specific gene expression profiles in the peripheral blood of patients with various types of neurological diseases. The working hypothesis is that differences in gene expression profiles after major limb amputation produce a unique phenotype through molecular interactions. Characteristics of PLP such as presence and severity of phantom pain may be modulated by changes in gene expression over the time in the post-amputation period. We will test the hypothesis that the gene expression profiles are different between PLP and non-PLP amputee patients. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary goal of this study is to: Identify predictive factors for the prognosis of PLP among the interactions between genetic variations, gene expressions, protein levels and other physiologic variables from the integrative genomic-phenomic analyses. The analyzed data from primary goals will contribute to the analysis for secondary goal. This integrative genomic-phenomic analysis can generate hypothesis for underlying pathways suggesting how gene expression changes in the serum can be linked to neurological diseases such as PLP. Phenotypic data will be determined from elements of the patient questionnaire used as potential covariates to classify PLP. The tertiary goal of this study is to: Verify candidate SNPs that are associated with PLP severity or duration in a group of non-Caucasian subjects. After identifying SNPs that are associated with PLP severity or duration in an ethnically homogenous sample, we will determine whether these findings can be generalized across different ethnic populations by comparing our genomic and proteomic findings from Caucasian and non-Caucasian subjects. The DNA and RNA analysis will be the same for both groups, and we will use principal component analysis to determine if SNPs identified in the Caucasian group are similar for non-Caucasian subjects. While previous research has suggested that frequency of genomic markers vary among different ethnic groups, there has not been any evidence to suggest an association between PLP and ethnicity. We therefore hypothesize that there will be no difference between PLP associated genes in the Caucasian group and the non-Caucasian group. | — |
Countries
Netherlands
Outcome results
None listed