Plasmonic Nanophotothermal Therapy of Atherosclerosis

Summary

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).

Conditions

• Stable Angina
• Heart Failure
• Atherosclerosis
• Multivessel Coronary Artery Disease

Interventions

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

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

DEVICE

Stenting

60 - in sirolimus-eluting stenting control

Sponsors & Collaborators

• Ural Institute of Cardiology

  collaborator OTHER

• De Haar Research Task Force

  collaborator INDUSTRY

• Ural Federal University

  collaborator OTHER

• Transfiguration Clinic

  collaborator UNKNOWN

• Ural State Medical University

  lead OTHER

Principal Investigators

• Jan Gabinsky, MD, PhD, DSc · Ural Institute of Cardiology

• Olga Kovtun, MD, PhD · Ural State Medical University

• Alexander Kharlamov, M.D., FESC, FACC, FEACVI · De Haar Research Task Force

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

45 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-04-01

Primary Completion

2009-04-01

Completion

2016-08-01

Countries

• Netherlands
• Russia

Study Locations