Overview

Silencing Inflammatory Activity by Injecting Nanocort in Patients at Risk for Atherosclerotic Disease

Status:
Unknown status
Trial end date:
1969-12-31
Target enrollment:
0
Participant gender:
All
Summary
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.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Treatments:
Methylprednisolone
Methylprednisolone acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Criteria
Inclusion Criteria:

- Population with target to background ratio of 2.2 of the aorta or carotid artery on
PET-CT

Exclusion Criteria:

- Current medical history of auto-immune disease/vasculitis, active inflammatory
diseases, Recent (<1 month prior to screening) or ongoing serious infection requiring
IV antibiotic therapy.

- Recent or current treatment with medications that may have a significant effect on
plaque inflammation as measured by plaque TBR, including but not limited to:

- Steroids for at least 6 weeks prior to baseline measurement and during study
(with the exception of inhaled acute use steroids).

- Biological based medicines (anti-TNF (ex. Infliximab), anti-IL-6 therapy (ex.
Tocilizumab) or anti-IL-1 (ex. anakinra)) within 8 weeks before the baseline
visit and during the study

- No other disease modifying antirheumatic drugs (DMRADS) within 6 weeks of
baseline and during study (such as cyclosporine, azatioprine, etc.)

- Known systemic disorders such as hepatic, renal, hematologic, and malignant diseases
or any clinically significant medical condition that could interfere with the conduct
of the study.

- Changes in dose or frequency of doses at least 6 weeks prior to baseline measurement
(unstable dosing) in angiotensin-converting enzyme (ACE) inhibitors (ACE-I) or
angiotensin-receptor blockers (ARBs), non-statin lipid-modifying therapy,
thiazolidinediones, inhaled steroids, or leukotriene modifying agents, nonsteroidal
anti-inflammatory drugs (NSAIDS), and cyclo-oxygenase-2 inhibitors (COXIBs)

- Standard contra-indications to MRI, 18FDG PET, and CT based on physicians experience
and current practices

- Current medical history of poorly controlled diabetes defined as hemoglobin A1c
(HbA1c) >7.5%.

- Current medical history of drug or alcohol abuse within 12 months prior to screening.

- History of anaphylaxis, anaphylactoid (resembling anaphylaxis) reactions, or severe
allergic responses.

- Inability or unwillingness to comply with the protocol requirements, or deemed by
investigator to be unfit for the study.

- Subject has planned cardiac surgery, PCI or carotid stenting, or major non-cardiac
surgery during the course of the study period or for 14 days after the last treatment.

- Use of any investigational drug in the 3 months prior to study drug administration.

- Use of insulin or any oral anti-diabetic (except metformin) in the 30 days prior to
baseline measurements. Those subjects who are taking metformin may be included in the
study if they are on a stable dose for at least 4 weeks and have a HbA1c <7.5%.

- Any contraindications for corticosteroid infusions (for example, but not limited
current infections or vaccinations)