Ignite Creation Date:
2024-05-05 @ 5:25 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00455403
Status:
COMPLETED
Last Update Posted:
2021-12-15
First Post:
2007-03-30
Brief Title:
Atheroma Reduction With Chloroquine in Patients With the Metabolic Syndrome ARCH-MS
Sponsor:
Washington University School of Medicine
Organization:
Washington University School of Medicine
Study Overview
Official Title:
Genotoxic Stress Atherosclerosis and Metabolic Syndrome- Aim 3
Status:
COMPLETED
Status Verified Date:
2021-12
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:
ARCH-MS
Brief Summary:
Metabolic syndrome consists of a group of co-occuring conditions that increase an individuals risk of developing heart disease stroke and diabetes The purpose of this study is to evaluate the long-term effectiveness of chloroquine a protein-activation medication at reducing the progression of atherosclerosis in patients with the metabolic syndrome
Sub-study Vascular endothelial growth factorVEGFand Cardiometabolic Risk The purpose is to determine if the association of VEGF with atherosclerosis indicates that it should be a marker of the disorder
Sub-study Vascular endothelial growth factorVEGFand Cardiometabolic Risk The purpose is to determine if the association of VEGF with atherosclerosis indicates that it should be a marker of the disorder
Detailed Description:
Metabolic syndrome is one of the most common disorders in industrialized countries It consists of abnormal serum lipids glucose intolerance elevated blood pressure and central obesity in the setting of insulin resistance The syndrome substantially increases the risk of developing diabetes and vascular disease but there is no clear unifying approach to treat this disorder In animals activation of the protein ataxia telangiectasia mutated ATM using the antimalarial drug chloroquine improves features of metabolic syndrome and decreases atherosclerosis a build-up of fatty plaque within arteries The purpose of this study is to examine the effect of long-term treatment with low doses of chloroquine on atherosclerosis in people with metabolic syndrome
At a baseline study visit participants will undergo an ultrasound of the neck to evaluate carotid artery intima-media thickness IMT and MRI to evaluate plaque composition In addition blood will be collected for laboratory testing and blood pressure will be measured Participants will then be randomly assigned to receive either placebo or chloroquine Study visits will occur every 3 months for 1 year At each visit blood pressure will be measured and blood will be collected At Months 6 and 12 a repeat ultrasound will be performed At month 12 a repeat carotid MRI is performed Participants will attend one follow-up visit at Month 24 and will undergo a final ultrasound
Sub-Study VEGF and Cardiometabolic Risk This is an observational case-study of existing baseline plasma and carotid intimal-medial thickness measurements VEGF is also closely linked to vascular disease From cell culture and animal models it is known that VEGF is increased in atherosclerotic lesions It is controversial whether that relationship is causative or reparative Both pro- and anti-VEGF therapies have been proposed for atherosclerosis However the association of VEGF with atherosclerosis indicates that it should be a marker of the disorder which is the hypothesis we wish to test No previous studies of circulating VEGF have been published
Other markers may be related to vascular disease or VEGF in this dataset Tumor necrosis factor TNF-alpha results in increased expression of VEGF and may be correlated positively with VEGF By Erenna Technology testing cardiac troponin I can be measured at levels much lower than current clinical assays and is expected to be elevated in ischemia but not necessarily in the stable vascular disease anticipated in our subjects High sensitivity C-reactive protein hsCRPhas been proposed as a marker for vascular disease that merits drug treatment in its own right and may also be correlated with VEGF and vascular disease However currently the relationship between hsCRP and vascular disease is not completely clear
For this preliminary VEGF study observational data from the baseline only will be studied Baseline testing includes carotid artery intimal-medial thickness carotid MRI lipid panel complete blood count comprehensive metabolic chemistry panel Thyroid-stimulating hormone TSH and glucose tolerance test with plasma insulin and glucose responses Plasma collected at baseline approximately 1 ml will be transferred to Singulex on dry ice Samples will be coded but will not contain patient identifiers Erenna Technology assays will be done for VEGF-A cardiac troponin ITNF-alpha interleukin-6 interleukin-17A and other cytokines at Singulex This method utilizes single-photon counting of visible light to improve assay sensitivity Separately Washington Universitys Core Lab for Clinical Studies CLCS will determine hsCRP
At a baseline study visit participants will undergo an ultrasound of the neck to evaluate carotid artery intima-media thickness IMT and MRI to evaluate plaque composition In addition blood will be collected for laboratory testing and blood pressure will be measured Participants will then be randomly assigned to receive either placebo or chloroquine Study visits will occur every 3 months for 1 year At each visit blood pressure will be measured and blood will be collected At Months 6 and 12 a repeat ultrasound will be performed At month 12 a repeat carotid MRI is performed Participants will attend one follow-up visit at Month 24 and will undergo a final ultrasound
Sub-Study VEGF and Cardiometabolic Risk This is an observational case-study of existing baseline plasma and carotid intimal-medial thickness measurements VEGF is also closely linked to vascular disease From cell culture and animal models it is known that VEGF is increased in atherosclerotic lesions It is controversial whether that relationship is causative or reparative Both pro- and anti-VEGF therapies have been proposed for atherosclerosis However the association of VEGF with atherosclerosis indicates that it should be a marker of the disorder which is the hypothesis we wish to test No previous studies of circulating VEGF have been published
Other markers may be related to vascular disease or VEGF in this dataset Tumor necrosis factor TNF-alpha results in increased expression of VEGF and may be correlated positively with VEGF By Erenna Technology testing cardiac troponin I can be measured at levels much lower than current clinical assays and is expected to be elevated in ischemia but not necessarily in the stable vascular disease anticipated in our subjects High sensitivity C-reactive protein hsCRPhas been proposed as a marker for vascular disease that merits drug treatment in its own right and may also be correlated with VEGF and vascular disease However currently the relationship between hsCRP and vascular disease is not completely clear
For this preliminary VEGF study observational data from the baseline only will be studied Baseline testing includes carotid artery intimal-medial thickness carotid MRI lipid panel complete blood count comprehensive metabolic chemistry panel Thyroid-stimulating hormone TSH and glucose tolerance test with plasma insulin and glucose responses Plasma collected at baseline approximately 1 ml will be transferred to Singulex on dry ice Samples will be coded but will not contain patient identifiers Erenna Technology assays will be done for VEGF-A cardiac troponin ITNF-alpha interleukin-6 interleukin-17A and other cytokines at Singulex This method utilizes single-photon counting of visible light to improve assay sensitivity Separately Washington Universitys Core Lab for Clinical Studies CLCS will determine hsCRP
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| P50HL083762 | NIH | None | httpsreporternihgovquickSearchP50HL083762 |