Plasmonic Nanophotothermal Therapy of Atherosclerosis (NANOM-FIM)
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ClinicalTrials.gov Identifier: NCT01270139 |
Recruitment Status :
Completed
First Posted : January 5, 2011
Results First Posted : August 30, 2012
Last Update Posted : March 17, 2021
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The investigators hypothesize that the nanoburning is a very challenging technique to demolish and reverse the plaque especially in combination with stem cell technologies promising the functional restoration of the vessel wall.
The completed (in July 2012) interventional three arms (n=180) first-in-man trial (the NANOM-FIM trial) assessed (NCT01270139) the safety and feasibility of two delivery techniques for nanoparticles (NP), and plasmonic photothermal therapy (PPTT) of atherosclerotic lesions. Patients were assigned in a 1:1:1 ratio to receive either (1) nano-intervention with delivery of silica-gold NP in mini-surgery implanted bioengineered on-artery patch (n=60), or (2) nano-intervention with delivery of silica-gold iron-bearing NP with targeted micro-bubbles or stem cells in hands of magnetic navigation system (n=60) versus (3) stent implantation (n=60). The primary outcome was TAV at 12 months.
The observational prospective cohort analysis (an amendment to the protocol of August 29th 2012 with a decision to extend a 1-year study for another 4 years with the assessment of the 5-year clinical outcomes both retro- and prospectively) of the long-term clinical outcomes at the intention-to-treat population of 180 patients with CAD and angiographic SYNTAX score ≤22 enrolled initially to NANOM-FIM trial will be performed at 5 years after the intervention. The primary outcome will be a MACE-free survival. The secondary outcomes will be MACE, cardiac death, TLR (target lesion revascularization) and TVR (target vessel revascularization). Imaging endpoints will be assessed pre-, post- procedure and at 12-month follow-up. Clinical endpoints will be analyzed at the baseline and at 12 and 60-month follow-up (the release of results is expected after October 2016). Parameters of nanotoxicity will be assessed. The independent adjudication analysis of the clinical outcomes is scheduled in 2017-2019.
The subset post-hoc analysis will be conducted at 1- and 5-year follow-up (by the Amendment of August 29th 2012). At the first subset, patients underwent stenting with XIENCE V stent proximal to the site of nano-intervention (n=13). Subjects in the second subset were undergone drug-coated balloon pre-dilation with further nano-technique (n=20). Lesions in patients of the third subset were not prepared for the nano-approach (n=147) (neither stenting nor balloon angioplasty). The analysis will be performed and results will be released after 2018 with the same clinical outcomes.
This project and related manuscripts were not prepared or funded in any part by a commercial organization. Nanoparticles and biomedical equipment were supplied free for the study by the non-profit Agiko and De Haar Research Task Force (Rotterdam-Amsterdam, the Netherlands). All rights of the authors are reserved. The access of the international academic or governmental organizations to the essential and primary data of the trial is restricted by the Russian governmental authorities due to the interest of the Russian Federal Security Service (FSB).
Condition or disease | Intervention/treatment | Phase |
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Stable Angina Heart Failure Atherosclerosis Multivessel Coronary Artery Disease | Procedure: Transplantation of nanoparticles Procedure: Transplantation of iron-bearing nanoparticles Device: Stenting | Not Applicable |

Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 180 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Double (Participant, Investigator) |
Primary Purpose: | Treatment |
Official Title: | Plasmonic Photothermal Therapy of Flow-Limiting Atherosclerotic Lesions With Silica-Gold Nanoparticles: a First-in-Man Study |
Actual Study Start Date : | April 1, 2007 |
Actual Primary Completion Date : | April 1, 2009 |
Actual Study Completion Date : | August 1, 2016 |

Arm | Intervention/treatment |
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Experimental: Nano group
60 patients in Nano group were treated with transplantation of nanoparticles (NP), particularly with a bioengineered patch that was grown with allogenous stem cells pre-cultivated in the medium with NP. After the admission, patients were examined with QCA, and allocated to the trial. The implantation of the patch onto the artery was undergone by the minimally invasive cardiac surgery (MICS CABG) with fixation of the graft to the epicardial myocardium. MICS CABG implies a beating-heart multi-vessel heart surgery performed through several small incisions under direct vision through an anterolateral mini-thoracotomy in the 4th-6th intercostal spaces. The patients can expect high quality of life resuming all everyday activities within a few weeks of their operation. NP were activated with NIR laser at 7 days after the intervention. Patients were treated with bolus of bivalirudin on the day of NP detonation.
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Procedure: Transplantation of nanoparticles
60 patients into nanogroup with the use of 60/15-70/40 nm silica-gold nanoparticles (NPs) transplanted by endoscopic cardiac surgery in the composition of bioengineered on-artery patch grown on the basis of biopolymeric scaffold and host circulating CD45-CD34-CD73+CD105+ progenitor cells |
Active Comparator: Ferro group
60 patients in Ferro group were managed with transplantation of iron-bearing nanoparticles (NP), particularly with intracoronary infusion of allogenous stem cells or CD68 targeted micro-bubbles pre-cultivated in the medium with iron-bearing NP. Cells and/ or micro-bubbles were infused with QCA- and IVUS-guidance to the target coronary artery via micro-catheter on the day of admission. The destruction of CD68 targeted micro-bubbles was obtained by using a Sonos 5500 machine with an S3 transducer operating in ultraharmonic mode (transmit, 1.3MHz/ receive, 3.6 MHz) with a mechanical index of 1.5 and a depth of 4 cm. The AXIOM Artis dBC (Siemens) magnetic navigation system was used for precise delivery of NP to the atheroma through two permanent computer-controlled external magnets generating a navigational magnetic field of 0.08 Tesla in any direction. NP were detonated with NIR laser under the protection of anti-platelet therapy.
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Procedure: Transplantation of iron-bearing nanoparticles
60 - into ferro-magnetic group with 60/15-70/40 nm silica-gold iron-bearing NPs with delivery in hand of magnetic navigation system |
Stenting control
In case of control group (stenting control), XIENCE V stent was implanted to 60 patients. Patients with a single de novo native coronary stenosis of less than 12 mm lesion length, more than 50% stenosis and reference diameter of 3.0 mm as assessed by online QCA were stented by a single stent of 3.0 x 18 mm. The procedure of implantation had to be performed according to common interventional practices including the administration of intracoronary nitroglycerine 0.2 mg of glycerol trinitrate or isosorbide dinitrate and intra-arterial heparin (50-100 U/kg body weight). Predilation with a conventional balloon catheter was recommended before DES deployment according to the manufacturer's recommendation. The protocol recommended the study stent should cover 2 mm of non-diseased tissue on either side of the target lesion. Postdilatation was allowed with a balloon that was shorter than was the study device.
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Device: Stenting
60 - in sirolimus-eluting stenting control
Other Name: XIENCE V |
- Total Atheroma Volume [ Time Frame: at 12-month follow-up ]Total atheroma volume (TAV, plaque-media volume, mm3) at 12 months. Quantitative coronary angiography (QCA) and Intravascular Ultrasound (IVUS) were performed pre-, post-procedure and at 12-month follow-up after a bolus infusion of i.c. nitrate. QCA was undergone with the CAAS II analysis system (Pie Medical B.V., Maastricht, The Netherlands) with analysis of different QCA parameters such as minimal lumen diameter, maximum lumen diameter, reference diameter, diameter stenosis, lesion length, percent atheroma volume (PAV), total atheroma volume (TAV), and lumen volume.
- MACE (Major Adverse Cardiovascular Events)-Free Survival [ Time Frame: at 60 months follow-up ]MACE (major adverse cardiovascular events)-free survival reflects per cent of survived patients without MACE. An amendment to the protocol was approved on August 29th 2012 with a decision to extend a 1-year study for another 4 years with the assessment of the 5-year clinical outcomes both retro- and prospectively.
- Per Cent of Fibro-fatty Component [ Time Frame: at 12-month follow-up ]IVUS (intravascular ultrasound) and IVUS-VH (virtual histology) images were acquired simultaneously with a phased array 20 MHz intravascular ultrasound catheter EagleEye (Volcano Co., Rancho Cordova, CA, USA) with motorized pull-back at a constant speed of 0.5 mm/s. Four tissue components (necrotic core - red; dense calcium - white; fibrous - green; and fibro-fatty - light green or yellow) were identified with autoregressive classification systems. For each cross section stent struts were detected as areas of apparent dense calcium and necrotic core. All IVUS analysis was performed offline by a CoreLab of the Ural Institute of Cardiology.
- Event Free Survival [ Time Frame: at 12-month follow-up ]The Kaplan-Meier analysis of the cardiac event-free survival (failure-free survival). The end point in this study was cardiac event-free survival during follow-up, starting at randomization. Cardiac events included cardiac death, myocardial infarction and unintended revascularization. Cardiac death was defined as sudden death, death after the onset of symptoms suggestive of cardiac ischemia and death due to heart failure. Noncardiac death was defined as death due to all other causes. Myocardial infarction was defined as an increase in cardiac enzymes or new pathologic Q-waves on the ECG, or both. Unintended revascularization was defined as PTCA or CABG performed due to worsening of the patient's clinical condition, rather than the PTCA or CABG assigned by the revascularization team when patient management was determined.
- Restenosis Rate [ Time Frame: at 12-month follow-up ]Restenosis (stenosis>50%) rate
- Late Definite Thrombosis [ Time Frame: at 12-month follow-up ]Late definite thrombosis rate
- Coronary Vasomotion - Mean Lumen Diameter After Infusion of Acetylcholine 10-6 M [ Time Frame: at 12-month follow-up ]Coronary vasomotion was assessed with QCA. End-diastolic images of coronary arteries were evaluated at baseline, after intravascular infusion of acetylcholine (through a microcatheter at increasing doses up to 10-8, 10-7, 10-6 M with a washout period of at least five minutes between each dose), and after nitroglycerine application following acetylcholine (100 µg orally). In all patients, measurements were performed in two segments on site of intervention while 960 seconds. The artery diameter was calibrated against the contrast-filled tip of the catheter. Vasoconstriction to acetylcholine was defined as a 3% change of the mean lumen diameter after infusion of the maximal dose of acetylcholine. An investigator blinded to treatment group performed all measurements.
- Per Cent Atheroma Volume [ Time Frame: at 12-month follow-up ]Per cent atheroma volume (PAV, plaque burden, %). Quantitative coronary angiography (QCA) and Intravascular Ultrasound (IVUS) were performed pre-, post-procedure and at 12-month follow-up after a bolus infusion of i.c. nitrate. QCA was undergone with the CAAS II analysis system (Pie Medical B.V., Maastricht, The Netherlands) with analysis of different QCA parameters such as minimal lumen diameter, maximum lumen diameter, reference diameter, diameter stenosis, lesion length, percent atheroma volume (PAV), total atheroma volume (TAV), and lumen volume.
- Target Lesion Revascularization [ Time Frame: at 12-month follow-up ]Target lesion revascularization, per cent
- Per Cent of Fibrous Component [ Time Frame: at 12-month follow-up ]IVUS (intravascular ultrasound) and IVUS-VH (virtual histology) images were acquired simultaneously with a phased array 20 MHz intravascular ultrasound catheter EagleEye (Volcano Co., Rancho Cordova, CA, USA) with motorized pull-back at a constant speed of 0.5 mm/s. Four tissue components (necrotic core - red; dense calcium - white; fibrous - green; and fibro-fatty - light green or yellow) were identified with autoregressive classification systems. For each cross section stent struts were detected as areas of apparent dense calcium and necrotic core. All IVUS analysis was performed offline by a CoreLab of the Ural Institute of Cardiology.
- Per Cent of Necrotic Core [ Time Frame: at 12-month follow-up ]IVUS (intravascular ultrasound) and IVUS-VH (virtual histology) images were acquired simultaneously with a phased array 20 MHz intravascular ultrasound catheter EagleEye (Volcano Co., Rancho Cordova, CA, USA) with motorized pull-back at a constant speed of 0.5 mm/s. Four tissue components (necrotic core - red; dense calcium - white; fibrous - green; and fibro-fatty - light green or yellow) were identified with autoregressive classification systems. For each cross section stent struts were detected as areas of apparent dense calcium and necrotic core. All IVUS analysis was performed offline by a CoreLab of the Ural Institute of Cardiology.
- Per Cent of Calcium [ Time Frame: at 12-month follow-up ]IVUS (intravascular ultrasound) and IVUS-VH (virtual histology) images were acquired simultaneously with a phased array 20 MHz intravascular ultrasound catheter EagleEye (Volcano Co., Rancho Cordova, CA, USA) with motorized pull-back at a constant speed of 0.5 mm/s. Four tissue components (necrotic core - red; dense calcium - white; fibrous - green; and fibro-fatty - light green or yellow) were identified with autoregressive classification systems. For each cross section stent struts were detected as areas of apparent dense calcium and necrotic core. All IVUS analysis was performed offline by a CoreLab of the Ural Institute of Cardiology.
- Minimal Lumen Diameter [ Time Frame: at 12-month follow-up ]Minimal lumen diameter (MLD, mm)
- MACE [ Time Frame: at 60 months follow-up ]MACE includes per cent of patients with cardiac death. STEMI (ST-elevation myocardial infarction), non-STEMI, and TLR (target lesion revascularization). An amendment to the protocol was approved on August 29th 2012 with a decision to extend a 1-year study for another 4 years with the assessment of the 5-year clinical outcomes both retro- and prospectively.
- Cardiac Death [ Time Frame: at 60 months follow-up ]Cardiac death includes per cent of patients passed away due to any cardiac death. An amendment to the protocol was approved on August 29th 2012 with a decision to extend a 1-year study for another 4 years with the assessment of the 5-year clinical outcomes both retro- and prospectively.
- TLR (Target Lesion Revascularization) [ Time Frame: at 60 months follow-up ]TLR (target lesion revascularization) reflects per cent of patients with TLR. An amendment to the protocol was approved on August 29th 2012 with a decision to extend a 1-year study for another 4 years with the assessment of the 5-year clinical outcomes both retro- and prospectively.
- TVR (Target Vessel Revascularization) [ Time Frame: at 60 months follow-up ]TVR (target vessel revascularization) reflects per cent of patients with TVR. An amendment to the protocol was approved on August 29th 2012 with a decision to extend a 1-year study for another 4 years with the assessment of the 5-year clinical outcomes both retro- and prospectively.
- Mean Number of Membrane Defects on Membrane of Red Blood Cells [ Time Frame: at 60 months follow-up ]Mean number of membrane defects on membrane of red blood cells calculated with atomic force microscopy (AFM) in random patients. An amendment to the protocol was approved on August 29th 2012 with a decision to extend a 1-year study for another 4 years with the assessment of the 5-year clinical outcomes both retro- and prospectively.

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Ages Eligible for Study: | 45 Years to 65 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- age 45-65 years old
- male and female
- single- or multi-vessel CAD with flow-limiting lesions
- no indications for coronary artery bypass surgery (CABG)
- stable angina with indications for percutaneous coronary interventions (PCI)
- NYHA (New York Heart Association) I-III functional class of heart failure (HF)
- treated hypertension (in supine position: systole >140 mm Hg, diastole >90 mm Hg)
- de novo treated.
Exclusion Criteria:
- non-compliance,
- angiographic SYNTAX score ≥23
- history of myocardial infarction (MI), unstable angina, PCI or CABG, atrial fibrillation or other dysrhythmias, stroke
- presence of indications for CABG
- presence of contraindications for PCI or CABG
- NYHA IV functional class of HF
- diabetes mellitus (in case of fasting glucose >7.0 mM/L or random glucose >11.0 mM/L)
- untreated hypertension
- asthma
- known hypersensitivity or contraindications to anti-platelet drugs
- contrast sensitivity
- participation to any drug- or intervention-investigation during the previous 60 days

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01270139
Netherlands | |
De Haar Research Task Force | |
Amsterdam, North Holland, Netherlands, 1069CD | |
Russian Federation | |
Ural Center of Modern Nanotechnologies, Institute of Natural Sciences, Ural Federal University | |
Yekaterinburg, Sverdlovsk Oblast, Russian Federation, 620000 | |
Transfiguration Clinic | |
Yekaterinburg, Sverdlovsk Oblast, Russian Federation, 620078 | |
Ural Institute of Cardiology | |
Yekaterinburg, Sverdlovsk Oblast, Russian Federation, 620144 |
Study Director: | Jan Gabinsky, MD, PhD, DSc | Ural Institute of Cardiology | |
Study Chair: | Olga Kovtun, MD, PhD | Ural State Medical University | |
Principal Investigator: | Alexander Kharlamov, M.D., FESC, FACC, FEACVI | De Haar Research Task Force |
Study Data/Documents: Study Protocol

This is a protocol of NANOM-FIM trial released in Mendeley Datasets.

There is Atomic Force Microscopy data from random patients.
Publications of Results:
Other Publications:
Responsible Party: | Alexander Kharlamov, MD, FESC, FACC, FEACVI, Research manager, De Haar Research Task Force |
ClinicalTrials.gov Identifier: | NCT01270139 |
Other Study ID Numbers: |
NANOM-FIM |
First Posted: | January 5, 2011 Key Record Dates |
Results First Posted: | August 30, 2012 |
Last Update Posted: | March 17, 2021 |
Last Verified: | February 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | The raw data will be partially shared (a Protocol for NANOM-FIM trial and related DREAM project; raw data with atomic force microscopy and scanning electron microscopy) in Mendeley Datasets and ResearchGate without any additional dissemination. |
Supporting Materials: |
Study Protocol |
Time Frame: | The data-sets will be provided in Mendeley and ResearchGate being accompanied to the published articles in 2013-2020. |
Access Criteria: | There are no specific criteria, but the access to the raw data is partly restricted by the Russian Federal Security Service for indefinite time. |
URL: | https://doi.org/10.13140/2.1.3109.5847 |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
nanoparticles mesenchymal stem cell plasmonics |
atherosclerosis IVUS stenting |
Coronary Artery Disease Atherosclerosis Angina, Stable Heart Diseases Cardiovascular Diseases Coronary Disease Myocardial Ischemia |
Arteriosclerosis Arterial Occlusive Diseases Vascular Diseases Angina Pectoris Chest Pain Pain Neurologic Manifestations |