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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2012 by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA).
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
E.S.stroes, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT01601106
First received: October 13, 2011
Last updated: May 18, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Atherosclerosis
Inflammation
Drug: liposomal prednisolone
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • 18Fludeoxyglucose Positron emission computed tomography scan (18FDG PET-CT scan) [ Time Frame: Day 8-13 ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: September 2011
Estimated Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Liposomal prednisolone Drug: liposomal prednisolone
Two weekly dosages with 150 mg.
Placebo Comparator: Placebo control Drug: liposomal prednisolone
Two weekly dosages with 150 mg.
Drug: Placebo

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01601106

Contacts
Contact: Erik S. Stroes, MD PhD +31205665978 e.s.stroes@amc.uva.nl

Locations
Netherlands
Academic Medical Center Recruiting
Amsterdam, Netherlands, 1105AZ
Contact: Erik S Stroes, MD PhD    +31205665978    e.s.stroes@amc.uva.nl   
Principal Investigator: Erik S Stroes, MD PhD         
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
Principal Investigator: Erik S Stroes, MD PhD AIDS Malignancy Clinical Trials Consortium
  More Information

No publications provided

Responsible Party: E.S.stroes, Professor, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT01601106     History of Changes
Other Study ID Numbers: NL37190.018.11
Study First Received: October 13, 2011
Last Updated: May 18, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Atherosclerosis, inflammation

Additional relevant MeSH terms:
Inflammation
Atherosclerosis
Arteriosclerosis
Pathologic Processes
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Methylprednisolone acetate
Prednisolone acetate
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents

ClinicalTrials.gov processed this record on October 02, 2014