A Proof of Concept Study to Determine the Local Delivery and Efficacy of Nanocort

NCT01647685 | Unknown Phase 1 DMC

• 1 other identifier: NL39717.018.12
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

A promising strategy to reduce CVD is to directly target inflammation at the level of the vessel wall. A potential drawback of anti-inflammatory strategies pertains to the thin line between inhibiting 'inappropriate' inflammation versus inducing immuno-suppression. One of the strategies to limit systemic immunosuppression is to strive for local delivery and prolonged efficacy and low systemic burden of the drug by encapsulating the compound in liposomes. Liposome-encapsulated drugs efficiently target lesions and accumulate at a much higher extent at desired areas of interest. Thus, local delivery and prolonged efficacy can be very important tools to overcome the potential drawback anti-inflammatory drugs; namely an inappropriate immune suppression. In the present project, the investigators therefore aim to evaluate the delivery and superior efficacy of Nanocort above Prednison or placebo in patients with peripheral artery disease due to atherosclerosis. Because these patients will undergo an endarteriectomy the investigators will be able to collect atherosclerotic material after drug administration and thus evaluate the local delivery and compare the effects of Nanocort to Prednison or Placebo.

Conditions

Atherosclerosis

Keywords

Vesselwall inflammation; liposomal prednisolone

Outcome Measures

Primary Outcomes (1)

• Quantity of PEG liposomes in the atherosclerotic plaque and/ or in atherosclerotic macrophages as determined with a PEG antibody quantitative sandwich ELISA.

  Quantity of PEG liposomes in the atherosclerotic plaque and/ or in atherosclerotic macrophages as determined with a PEG antibody quantitative sandwich ELISA.

  Participation of patient: maximally 12 days (infusion 1 on day-10 (+/-2days), infusion 2 on day-3, operation and sample collection on day 0) Data assessment: average 4 months.

Secondary Outcomes (2)

• Differences between TNF-alpha levels in the supernatant of isolated macrophages from the atherosclerotic tissue as determined by quantitative sandwich ELISA

  Participation of patient: maximally 12 days (infusion 1 on day-10 (+/-2days), infusion 2 on day-3, operation and sample collection on day 0) Data assessment: average 4 months.

• Concentration of corticosteroids in plaque.

  Participation of patient: maximally 12 days (infusion 1 on day-10 (+/-2days), infusion 2 on day-3, operation and sample collection on day 0) Data assessment: average 4 months.

Study Arms (3)

Nanocort

ACTIVE COMPARATOR

Two weekly IV infusions of 144 mg Nanocort (PEG-liposomal prednisolone sodium phosphate).

Drug: Nanocort

Methylprednisolone

ACTIVE COMPARATOR

Methylprednisolone sodium succinate 125 mg infusion.

Drug: Methylprednisolone

Saline

PLACEBO COMPARATOR

Saline solution (same solution brand as used to dilute/prepare Nanocort injection)

Drug: Placebo

Interventions

Nanocort DRUG

Two weekly IV infusions of 150 mg Nanocort (PEG-liposomal prednisolone sodium phosphate).

Also known as: Nanocort (PEG-liposomal prednisolone sodium phosphate).

Nanocort

Methylprednisolone DRUG

Two weekly infusion iv methylprednisolone sodium succinate 125 mg infusion.

Also known as: Methylprednisolone, Solu-medrol

Methylprednisolone

Placebo DRUG

Saline solution (same solution brand as used to dilute/prepare Nanocort injection)

Also known as: NaCl 0.9%

Saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet the following criteria for study entry:
• Patients who are scheduled for endarterectomy due to peripheral artery disease.
• If using a statin, on stable therapy for at least 6 weeks prior to screening with no evidence of statin intolerance.
• For patients taking angiotensin-converting enzyme (ACE) inhibitors (ACE-I) or angiotensin-receptor blockers (ARBs), non-statin lipid-modifying therapy, thiazolidinediones, inhaled steroids, or leukotriene modifying agents, use of a stable dose for at least 6 weeks prior to baseline measurement.
• For patients taking Nonsteroidal anti-inflammatory drugs (NSAIDS), Cyclo-oxygenase-2 inhibitors (COXIBs), use of a stable dose for at least 6 weeks prior to baseline measurement.

You may not qualify if:

• Current medical history of Auto-immune disease/vasculitis, active inflammatory diseases, proven or suspected bacterial infections. 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, including but not limited to:
• Steroids for at least 6 weeks prior to baseline measurement and during study (with the exception of inhaled 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 disorder, such as hepatic, renal, hematologic or endocrine diseases, infections or malignancies, or any clinically significant medical condition that could interfere with the conduct of the study.
• Subjects with a known ulcus ventriculi or duodeni.
• Female subjects who are breastfeeding, pregnant or trying to get pregnant.
• History of anaphylaxis, anaphylactoid (resembling anaphylaxis) reactions, or severe allergic responses.
• History of hypersensitivity to methylprednisolone or any component of the formulation.
• Any history of myopathy or a history of neuromuscular disorders (e.s, myasthenia gravis).
• Any planned vaccinations.
• 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.
• Current medical history of drug or alcohol abuse within 12 months prior to screening.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

AMC

Amsterdam, Amsterdam, 1105AZ, Netherlands

RECRUITING

MeSH Terms

Conditions

Atherosclerosis

Interventions

Methylprednisolone; Methylprednisolone Hemisuccinate; Sodium Chloride

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• E S Stroes, MD PhD

  AIDS Malignancy Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

F M van der Valk, MD

CONTACT

0031 20 5668791; f.m.valkvander@amc.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor doctor

Study Record Dates

• First Submitted: June 28, 2012
• First Posted: July 23, 2012
• Study Start: May 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: July 23, 2012

Record last verified: 2012-05

Locations

NL (1)