NCT01601106: SILENCE

A Phase I/II, Single-Center, Randomized, Placebo-Controlled Study Evaluating the Therapeutic Efficacy of Intravenously Injected PEG-liposomal Prednisolone Sodium Phosphate (Nanocort®) in Subjects With Severe Inflamed Carotid or Aortic Atherosclerosis Plaques

Status unknown Phase 1/Phase 2 Last updated 18 May 2012

What this trial tests

Phase 1/Phase 2 trial testing liposomal prednisolone in Atherosclerosis in 30 participants. Status unknown.

Timeline

1 September 2011

Primary endpoint
1 May 2013

Quick facts

Lead sponsor	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Phase	Phase 1/Phase 2
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	30
Start date	1 September 2011
Primary completion	1 May 2013
Sites	1 location across Netherlands

Drugs / interventions tested

• liposomal prednisolone — full drug profile →
• Placebo

Conditions studied

• Atherosclerosis — all drugs for Atherosclerosis →
• Inflammation — all drugs for Inflammation →

Sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) — full company profile →

Who can join

50 and older, any sex, with Atherosclerosis or Inflammation. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• 18Fludeoxyglucose Positron emission computed tomography scan (18FDG PET-CT scan)
  Time frame: Day 8-13

Sponsor's own description

Cardiovascular disease(CVD) is the leading cause of morbidity and mortality in developed nations. CVD is primarily caused by atherosclerosis, a systemic disease characterized by lipid deposition in the subendothelial space with a concomitant, low-grade inflammatory reaction.(Fuster, Moreno et al. 2005) To date, most therapeutic interventions aimed at lowering CVD have thus far focused on modulating lipid levels, either lowering LDLc or increasing HDLc levels. Yet, since the introduction of statins 20 years ago, there have been few breakthroughs in the treatment of this disease. A promising strategy to reduce CVD is to directly target inflammation at the level of the vessel wall.(van Leuven, van Wijk et al.; Libby 2002) A potential drawback of anti-inflammatory strategies pertains to the thin line between inhibiting 'inappropriate' inflammation versus inducing immuno-suppression. Therefore, continuous low dosed anti-inflammatory drugs have great potential as novel treatment strategies. In the present project, the investigators propose to inject liposomal glucocorticoids intravenously in patients with an increased risk of atherosclerotic disease aiming to reduce vessel wall inflammation.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Macrophage-targeted nanomedicine for the diagnosis and treatment of atherosclerosis.
   Chen W, Schilperoort M, Cao Y, Shi J, et al · · 2022 · cited 370× · PMID 34759324 · DOI 10.1038/s41569-021-00629-x
2. Imaging and nanomedicine in inflammatory atherosclerosis.
   Mulder WJ, Jaffer FA, Fayad ZA, Nahrendorf M. · · 2014 · cited 147× · PMID 24898749 · DOI 10.1126/scitranslmed.3005101
3. Prednisolone-containing liposomes accumulate in human atherosclerotic macrophages upon intravenous administration.
   van der Valk FM, van Wijk DF, Lobatto ME, Verberne HJ, et al · · 2015 · cited 114× · PMID 25791806 · DOI 10.1016/j.nano.2015.02.021
4. Nanoparticles in the diagnosis and treatment of vascular aging and related diseases.
   Xu H, Li S, Liu YS. · · 2022 · cited 52× · PMID 35817770 · DOI 10.1038/s41392-022-01082-z
5. "Eat me" imaging and therapy.
   Bagalkot V, Deiuliis JA, Rajagopalan S, Maiseyeu A. · · 2016 · cited 37× · PMID 26826436 · DOI 10.1016/j.addr.2016.01.009
6. Pharmaceutical development and preclinical evaluation of a GMP-grade anti-inflammatory nanotherapy.
   Lobatto ME, Calcagno C, Otten MJ, Millon A, et al · · 2015 · cited 34× · PMID 25791805 · DOI 10.1016/j.nano.2015.02.020
7. Targeting macrophages with multifunctional nanoparticles to detect and prevent atherosclerotic cardiovascular disease.
   Nankivell V, Vidanapathirana AK, Hoogendoorn A, Tan JTM, et al · · 2024 · cited 23× · PMID 38696700 · DOI 10.1093/cvr/cvae099
8. Advancements in Macrophage-Targeted Drug Delivery for Effective Disease Management.
   Liu H, Lv H, Duan X, Du Y, et al · · 2023 · cited 23× · PMID 38026516 · DOI 10.2147/ijn.s430877