Ignite Creation Date:
2024-05-06 @ 8:12 AM
Last Modification Date:
2024-10-26 @ 11:57 AM
Study NCT ID:
NCT02683421
Status:
COMPLETED
Last Update Posted:
2019-11-21
First Post:
2016-01-22
Brief Title:
Evaluation of SC Injected Tc 99m Tilmanocept Localization in Active RA Subjects by SPECT and SPECTCT Imaging
Sponsor:
Navidea Biopharmaceuticals
Organization:
Navidea Biopharmaceuticals
Study Overview
Official Title:
Evaluation of Subcutaneous SC Injected Tc 99m Tilmanocept Localization in Active Rheumatoid Arthritis RA Subjects by SPECT and SPECTCT Imaging
Status:
COMPLETED
Status Verified Date:
2019-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Determine the localization of Tc 99m tilmanocept by SPECT and SPECTCT imaging in subjects with active RA and concordance with clinical symptomology
Detailed Description:
While many types of cells including T-cells B-cells dendritic cells and activated synovial fibroblasts contribute significantly to the establishment and maintenance of the pathology of rheumatoid arthritis RA Ma et al Noack et al Bugatti et al Boissier et al Tran et al macrophages play a critical role in RA Kinne et al They produce most of the tumor necrosis factor alpha TNFα that drives and perpetuates the inflammatory cycle in RA Leizer et al Westra et al Hamilton et al Keffer et al Noack et al Bugatti et al Boissier et al Tran et al Kinne et al Zwerina et al Feldman et al Schett et al In the synovial sublining of a joint affected by RA macrophages are the dominant cell type Kraan et al Cutolo et al In the inflamed joint as a whole macrophages in RA patients make up at least 30-40 of all cells Kennedy et al Furthermore macrophages participate directly in the destruction of bone and cartilage Ma et al Activated macrophage populations and synoviocytes are the predominant cell types at the interface between pannus and cartilage and secrete destructive proteases in abundance Bresnihan et al As a result it may not be surprising that synovial macrophage numbers-but not the numbers of other immune cell types-correlate with radiographically determined joint destruction in RA Mulherin et al Yanni et al While macrophages may play a role in other pathologies that cause joint pain and inflammation the degree to which macrophages are involved in the pathological process of RA and the sheer mass or volume of macrophages that infiltrate the joints inflamed due to RA differentiates RA from other rheumatic diseases Therefore detection of the density or numbers of macrophages in inflamed joints may permit differentiation of patients with RA from those with other causes of arthritis In addition it is known that the RA pathology begins significantly before perhaps years before the onset of symptoms ie joint pain and inflammation and well before the beginning of bone destruction Deane et al El-Gabalawy et al Macrophage infiltration of synovial tissues precedes development of clinical signs of RA in animal studies Kraan et al In humans macrophage infiltrations of synovial tissues are present when RA patients first develop clinical symptoms Demoruelle et al van de Sande et al Therefore detection of the density or numbers of macrophages in inflamed joints may facilitate more sensitive and specific identification of RA patients as soon as they present with symptoms and early in the course of their illnesses when DMARDs are likely to be most effective
An interesting and important observation that has been made in many studies is that the number of macrophages in synovial tissue and particularly in the synovial sublining declines in RA patients when they are given DMARD therapy Hamilton et al Furthermore the degree to which synovial macrophage numbers decline is correlated with the magnitude of the DMARD DAS28 with changes in sublining macrophage numbers as determined by biopsies and found a significant correlation between the change in the number of macrophages and the change in DAS28 Pearson correlation 0874 p 001 Haringman et al The authors of this study have confirmed these findings in two additional studies which used slightly different methodologies Bresnihan et al Bresnihan et al This correlation between declining macrophage numbers and the efficacy of DMARD therapy appears to be largely independent of the kind of DMARD therapy being investigated Hamilton et al Kinne et al Franz et al Kraan et al Catrina et al Cunnane et al Vieira-Sousa et al These findings indicate that assaying the number of macrophages in inflamed joints of patients with RA could be used as an objective measure of the efficacy of DMARD therapy These findings further suggest that assaying the number of macrophages in inflamed joints of patients with RA could be used in clinical studies as a biomarker of clinical response for potential new RA therapeutics The problem with current methodologies is that macrophage numbers and densities need to be determined with synovial biopsies This is obviously an invasive procedure that samples only a small portion of the inflamed synovial tissue and is painful and unpleasant for the patient What would be preferable and likely more accurate is an imaging protocol such as the one proposed in this application that can assay synovial macrophages more completely and less invasively
An interesting and important observation that has been made in many studies is that the number of macrophages in synovial tissue and particularly in the synovial sublining declines in RA patients when they are given DMARD therapy Hamilton et al Furthermore the degree to which synovial macrophage numbers decline is correlated with the magnitude of the DMARD DAS28 with changes in sublining macrophage numbers as determined by biopsies and found a significant correlation between the change in the number of macrophages and the change in DAS28 Pearson correlation 0874 p 001 Haringman et al The authors of this study have confirmed these findings in two additional studies which used slightly different methodologies Bresnihan et al Bresnihan et al This correlation between declining macrophage numbers and the efficacy of DMARD therapy appears to be largely independent of the kind of DMARD therapy being investigated Hamilton et al Kinne et al Franz et al Kraan et al Catrina et al Cunnane et al Vieira-Sousa et al These findings indicate that assaying the number of macrophages in inflamed joints of patients with RA could be used as an objective measure of the efficacy of DMARD therapy These findings further suggest that assaying the number of macrophages in inflamed joints of patients with RA could be used in clinical studies as a biomarker of clinical response for potential new RA therapeutics The problem with current methodologies is that macrophage numbers and densities need to be determined with synovial biopsies This is obviously an invasive procedure that samples only a small portion of the inflamed synovial tissue and is painful and unpleasant for the patient What would be preferable and likely more accurate is an imaging protocol such as the one proposed in this application that can assay synovial macrophages more completely and less invasively
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None