Ignite Creation Date:
2024-05-05 @ 11:51 PM
Last Modification Date:
2024-10-26 @ 10:41 AM
Study NCT ID:
NCT01436123
Status:
TERMINATED
Last Update Posted:
2015-05-19
First Post:
2011-09-14
Brief Title:
Plasmonic Photothermal and Stem Cell Therapy of Atherosclerosis Versus Stenting
Sponsor:
Ural State Medical University
Organization:
Ural State Medical University
Study Overview
Official Title:
Plasmonic Photothermal and Stem Cell Therapy of Atherosclerosis With The Use of Gold Nanoparticles With Iron Oxide-Silica Shells Versus Stenting
Status:
TERMINATED
Status Verified Date:
2015-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
The study was terminated under the political pressure of the Federal Security Service of the Russian Federation FSB and the Russian Society of Cardiology
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NANOM PCI
Brief Summary:
Intensive therapy with rosuvastatin 40 mg and ApoA-I Milano reduces the total atheroma volume TAV up to 638 or 141 mm3 respectively Our previous bench studies PLASMONICS and NANOM First-in-Man trial documented TAV reduction up to unprecedented 794 and 603 mm3 respectively with high level of safety and feasibility
The completed randomized two arm 11 study NANOM-PCI with parallel assignment n62 assessed NCT01436123 the safety and feasibility of the delivery technique for nanoparticles NP using micro-injection catheter with intravascular intramural injection of allogeneous stem cells carrying NP after MSCT- IVUS- and OCT-guided mapping of the vessel and plasmonic photothermal therapy of atherosclerosis combined with stenting Nano group n32 versus stenting with Xience V cage Stenting group n30 The primary outcome was TAV at 12 months
The mean reduction of TAV at 12 months in Nano group was -841 mm3 95 CI SD 283 min -524 mm3 max -991 mm3 p005 versus 124 mm3 in case of stenting p005 between groups 4262 patients 68 in Nano group passed the Glagov threshold of a 40 plaque burden with mean plaque burden PB 362 95 CI SD 93 min 309 max 445 The increase of the minimal lumen diameter was 612 and 633 at 12 month follow up in groups respectively The serial assessment of VH-IVUS showed a significant decrease at 12 months in the dense calcium area fibrous and fibro-fatty tissue with fulminant necrosis due to thermolysis in Nano-group whereas an increase of fibrous and fibro-fatty components in stenting arm We have documented 2 vs 3 cases of the definite thrombosis and 3 vs 5 cases of target lesion revascularization in groups respectively The analysis of the event-free survival of the ongoing clinical follow-up shows the significantly lower risk of cardiovascular death in Nano group if compare with conventional stenting 934 vs 867 p005
Plasmonic resonance-mediated therapy using noble-metal NP associated with significant regression of coronary atherosclerosis Tested delivery approach has acceptable safety and efficacy for atheroregression below a 40 PB
The investigators hypothesize that multistep approach with the use of stent in acute care unit and then subsequent transcatheter micro-injection with nanoparticles can resolve atherosclerosis stop and regress atherogenesis remodulate or even rejuvenate arteries Stem cells in patch can be good carriers for nanoparticles as well as high-effective metabolic vectors paracrine-like regulation of alive cells and via bioactive products of cell lysis after detonation of nanoparticles for the treatment of plaque on site Gold nanoparticles with silica-iron oxide shells promise high-energy plasmonic photothermic burning or melting effect under the near-infrared laser irradiation onto the lesion Thus the investigators expect complex two-side effect on the plaque with protected lumen and adventitia
Novel discoveries in atherogenesis and development of nanobiotechnologies with potentials for the management of atherosclerosis leads us to the quest of new approaches The investigators still cannot really effectively treat atherosclerosis
The investigators management is more symptomatic and lipid-pool or inflammation-oriented The investigators cannot manage non-organic part mineral deposits calcified necrotic core partially collagen and fibrotic tissue and total plaque volume Surgery and invasive procedures is just focused on blood flow restoration just manipulate the form of plaque concerns of clinical and technical restrictions incl alien body - stent risk of restenosis or subacute fatal in-stent atherothrombosis graft survival occlusion surgery-related complications High rate of short- and long-term complications and readmissions Regression of atherosclerosis in fact is still a dream The investigators offer an alternative to stenting and may be cardiac artery bypass surgery CABG Our approach can really allow to rejuvenate arteries Plasmonic photothermal therapy PPTT can burn plaque but stem cells and bioengineered structures promise restoration of the vessel wall
Our personal previous data showed that PPTT can 16-fold reduce a volume of plaque with most optimal long-term result in subsets with the use of SPCs as a delivery approach The most optimal delivery systems of NPs into the plaque are the on-artery bioengineered patch and ferro-magnetic approach
The completed randomized two arm 11 study NANOM-PCI with parallel assignment n62 assessed NCT01436123 the safety and feasibility of the delivery technique for nanoparticles NP using micro-injection catheter with intravascular intramural injection of allogeneous stem cells carrying NP after MSCT- IVUS- and OCT-guided mapping of the vessel and plasmonic photothermal therapy of atherosclerosis combined with stenting Nano group n32 versus stenting with Xience V cage Stenting group n30 The primary outcome was TAV at 12 months
The mean reduction of TAV at 12 months in Nano group was -841 mm3 95 CI SD 283 min -524 mm3 max -991 mm3 p005 versus 124 mm3 in case of stenting p005 between groups 4262 patients 68 in Nano group passed the Glagov threshold of a 40 plaque burden with mean plaque burden PB 362 95 CI SD 93 min 309 max 445 The increase of the minimal lumen diameter was 612 and 633 at 12 month follow up in groups respectively The serial assessment of VH-IVUS showed a significant decrease at 12 months in the dense calcium area fibrous and fibro-fatty tissue with fulminant necrosis due to thermolysis in Nano-group whereas an increase of fibrous and fibro-fatty components in stenting arm We have documented 2 vs 3 cases of the definite thrombosis and 3 vs 5 cases of target lesion revascularization in groups respectively The analysis of the event-free survival of the ongoing clinical follow-up shows the significantly lower risk of cardiovascular death in Nano group if compare with conventional stenting 934 vs 867 p005
Plasmonic resonance-mediated therapy using noble-metal NP associated with significant regression of coronary atherosclerosis Tested delivery approach has acceptable safety and efficacy for atheroregression below a 40 PB
The investigators hypothesize that multistep approach with the use of stent in acute care unit and then subsequent transcatheter micro-injection with nanoparticles can resolve atherosclerosis stop and regress atherogenesis remodulate or even rejuvenate arteries Stem cells in patch can be good carriers for nanoparticles as well as high-effective metabolic vectors paracrine-like regulation of alive cells and via bioactive products of cell lysis after detonation of nanoparticles for the treatment of plaque on site Gold nanoparticles with silica-iron oxide shells promise high-energy plasmonic photothermic burning or melting effect under the near-infrared laser irradiation onto the lesion Thus the investigators expect complex two-side effect on the plaque with protected lumen and adventitia
Novel discoveries in atherogenesis and development of nanobiotechnologies with potentials for the management of atherosclerosis leads us to the quest of new approaches The investigators still cannot really effectively treat atherosclerosis
The investigators management is more symptomatic and lipid-pool or inflammation-oriented The investigators cannot manage non-organic part mineral deposits calcified necrotic core partially collagen and fibrotic tissue and total plaque volume Surgery and invasive procedures is just focused on blood flow restoration just manipulate the form of plaque concerns of clinical and technical restrictions incl alien body - stent risk of restenosis or subacute fatal in-stent atherothrombosis graft survival occlusion surgery-related complications High rate of short- and long-term complications and readmissions Regression of atherosclerosis in fact is still a dream The investigators offer an alternative to stenting and may be cardiac artery bypass surgery CABG Our approach can really allow to rejuvenate arteries Plasmonic photothermal therapy PPTT can burn plaque but stem cells and bioengineered structures promise restoration of the vessel wall
Our personal previous data showed that PPTT can 16-fold reduce a volume of plaque with most optimal long-term result in subsets with the use of SPCs as a delivery approach The most optimal delivery systems of NPs into the plaque are the on-artery bioengineered patch and ferro-magnetic approach
Detailed Description:
Nanoparticles NPs are quite safe for an organism but entire kinetics is mostly unknown The most dangerous approach with lowest level of efficacy and safety is a delivery of NPs with microbubbles SP and mesenchymal SPCs have the similar efficacy as a local delivery system with a lot of beneficial properties such as anti-inflammative anti-apoptotic and multi-metabolic effects leading to the plaque degradation and artery rejuvenation Thus nanoburning is very challenging technique to demolish and reverse the plaque especially in combination with stem cell technologies promising functional restoration of the vessel wall and can be an alternative to stenting
Altering general strategy the investigators generally offer
1 The investigators dont need a therapy only with harvested stem cells not so effective but more provocative the investigators have to manage host resident stem cells on site local in-artery infusion with growth factors cytokines or systemic potentiation but risk of side effects and adverse events is high
2 Regular intravenous systemic therapy with modified BM bone marrow circulating progenitor and iPS induced pluripotent stem cells might be beneficial for prevention of diseases and rejuvenation of tissues and organs - but the system as whole will be compromised the investigators can store stem cells of each individual to use for cell therapy or bioengineering
3 The best way - development of bioengineered constructions through life to transplant a bioartificial organ on request
4 Multi-step invasive treatment of atherosclerosis - 1 biodegradable stenting in ACU acute care unit or preventively with no restenosis and no acute atherothrombosis risk profile 2 regular systemic or local stem cell therapy or with cytokines 3 on-artery MSCs mesenchymal stem cells-related bioengineered patch with silica-gold iron-bearing NPs SCs stem cells as carriers for NPs with transduction in hands of magnetic fields for local elimination of plaque and subsequent rejuvenation of artery wall
Our new approach challenging modern therapy of atherosclerosis include
1 BIODEGRADABLE STENTS - for 6-24 months period under the soft short-term antithrombotic therapy resolving concerns with stenosis lumen steered remodeling no hemorrhages no alien metal body no concerns with further CABG minimal inflammation
2 INTRAVENOUS NON-SPECIFIC SYSTEMIC STEM CELL THERAPY - before and after stenting - launch repair effects in vessel beneficial effects for ischemic or injured tissues
3 ON-ARTERY BIOENGINEERED PATCH transplantation with NPs or MICRO-INFUSION of stem cells bearing NP - grown with MSCs and NPs bovine pericardium scaffold 3-6 weeks to grow a thin structure recover cells before or during stenting multi-effects due to migration of SCs bioactive products of lysis
4 PLASMONIC PHOTOTHERMAL THERAPY - melting and burning effects - direct degradation bioactive products of stem cells lysis further migration of SCs from patch
Potential expected disadvantages of our approach Necessity of the special precise delivery technique Lost function of artery - irreparable pro-fibrotic and pro-inflammative damage - necessity of another clinical approach for restoration of tissue may be with stem cells Threat of acute fatal atherothrombosis due to rupture of vulnerable plaque - verification of the optimal antithrombotic therapy Cannot treat non-organic part of plaque - necessity of the special therapy for mineral deposits calcified necrotic core fibrotic sites - solution using stem cells Harm of potent detrimental adverse effects - vapor bubbling boiling of cytoplasm and ECM with subsequent lysis of cells and provocation of pro-apoptotic cascades acoustic and shock waves due to plasma-generated laser-related detonation of nanoshells in tissue - need regenerative therapy type of SCs conditions and way of transplantation Culturing Sorting Erratic unsteered heating - surrounding tissue of the site of interest can achieve a temperature until 38-39 But at the site of burning final temperature can be at about 50-180 C cauterization searing melting effect with consequent pro-fibrotic effect - need regenerative therapy and clarification of energy options
Altering general strategy the investigators generally offer
1 The investigators dont need a therapy only with harvested stem cells not so effective but more provocative the investigators have to manage host resident stem cells on site local in-artery infusion with growth factors cytokines or systemic potentiation but risk of side effects and adverse events is high
2 Regular intravenous systemic therapy with modified BM bone marrow circulating progenitor and iPS induced pluripotent stem cells might be beneficial for prevention of diseases and rejuvenation of tissues and organs - but the system as whole will be compromised the investigators can store stem cells of each individual to use for cell therapy or bioengineering
3 The best way - development of bioengineered constructions through life to transplant a bioartificial organ on request
4 Multi-step invasive treatment of atherosclerosis - 1 biodegradable stenting in ACU acute care unit or preventively with no restenosis and no acute atherothrombosis risk profile 2 regular systemic or local stem cell therapy or with cytokines 3 on-artery MSCs mesenchymal stem cells-related bioengineered patch with silica-gold iron-bearing NPs SCs stem cells as carriers for NPs with transduction in hands of magnetic fields for local elimination of plaque and subsequent rejuvenation of artery wall
Our new approach challenging modern therapy of atherosclerosis include
1 BIODEGRADABLE STENTS - for 6-24 months period under the soft short-term antithrombotic therapy resolving concerns with stenosis lumen steered remodeling no hemorrhages no alien metal body no concerns with further CABG minimal inflammation
2 INTRAVENOUS NON-SPECIFIC SYSTEMIC STEM CELL THERAPY - before and after stenting - launch repair effects in vessel beneficial effects for ischemic or injured tissues
3 ON-ARTERY BIOENGINEERED PATCH transplantation with NPs or MICRO-INFUSION of stem cells bearing NP - grown with MSCs and NPs bovine pericardium scaffold 3-6 weeks to grow a thin structure recover cells before or during stenting multi-effects due to migration of SCs bioactive products of lysis
4 PLASMONIC PHOTOTHERMAL THERAPY - melting and burning effects - direct degradation bioactive products of stem cells lysis further migration of SCs from patch
Potential expected disadvantages of our approach Necessity of the special precise delivery technique Lost function of artery - irreparable pro-fibrotic and pro-inflammative damage - necessity of another clinical approach for restoration of tissue may be with stem cells Threat of acute fatal atherothrombosis due to rupture of vulnerable plaque - verification of the optimal antithrombotic therapy Cannot treat non-organic part of plaque - necessity of the special therapy for mineral deposits calcified necrotic core fibrotic sites - solution using stem cells Harm of potent detrimental adverse effects - vapor bubbling boiling of cytoplasm and ECM with subsequent lysis of cells and provocation of pro-apoptotic cascades acoustic and shock waves due to plasma-generated laser-related detonation of nanoshells in tissue - need regenerative therapy type of SCs conditions and way of transplantation Culturing Sorting Erratic unsteered heating - surrounding tissue of the site of interest can achieve a temperature until 38-39 But at the site of burning final temperature can be at about 50-180 C cauterization searing melting effect with consequent pro-fibrotic effect - need regenerative therapy and clarification of energy options
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