High-Field MRI Iron-Based Contrast-Enhanced Characterization of Multiple Sclerosis and Demyelinating Diseases

NCT01973517 | Withdrawn

• 1 other identifier: 27423-001
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

Feraheme (ferumoxytol) is FDA-approved for iron supplementation and is composed of iron oxide nanoparticles classified among the ultra-small superparamagnetic iron oxides (USPIO). In this project we hypothesize that Feraheme could become a sensitive and specific marker of active inflammation in multiple sclerosis. We will explore this hypothesis taking advantage of ultra high field strength (7T) MRI to further increase the effectiveness of the contrast agent Feraheme at revealing inflammatory activity.

Conditions

Multiple Sclerosis

Keywords

Multiple sclerosis; MRI; USPIO; Ferumoxytol; Feraheme

Outcome Measures

Primary Outcomes (1)

• Number and location of enhancing brain lesions seen on 7 tesla MRI following Feraheme administration.

  Magnetic resonance images of the brains of subjects will be evaluated independently by two expert readers blinded to the demographic and clinical data. The location and number of multiple sclerosis lesions that enhance following Feraheme administration will be recorded. These lesions will be compared with non-enhancing lesions and lesions that enhance with gadolinium-based contrast.

  Baseline

Secondary Outcomes (1)

• Number and location of enhancing brain lesions seen on 7 tesla MRI following gadolinium-based contrast administration.

  Baseline

Study Arms (1)

Relapsing Remitting MS

Patients with relapsing remitting multiple sclerosis will be imaged under high-field (7T) MRI prior to and following administration of gadolinium-based contrast (0.1 mmol/kg IV). Afterwards, they will be administered Feraheme 5mg/kg IV via slow push, and they will return 24 hours or later after pharmaceutical administration for post-Feraheme MR imaging.

Drug: Feraheme; Drug: Gadolinium-based contrast

Interventions

Feraheme DRUG

Patients with relapsing remitting multiple sclerosis will be administered Feraheme 5mg/kg IV via slow push once and imaged under high-field MRI at least 24 hours following administration, to allow for adequate clearance of intravascular pharmaceutical.

Also known as: Ferumoxytol

Relapsing Remitting MS

Gadolinium-based contrast DRUG

Patients with relapsing remitting multiple sclerosis will be administered gadolinium-based contrast at a dose of 0.1 mmol/kg IV once and imaged under high-field MRI immediately following administration.

Also known as: Gadolinium

Relapsing Remitting MS

Eligibility Criteria

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

Study Population

Population will be composed of patients with the diagnosis of relapsing remitting multiple sclerosis (MS) who are followed at the Stanford Neurosciences Clinic.

You may qualify if:

• Patients will be included if they are at least 18 years old and meet the revised diagnostic criteria for multiple sclerosis, relapsing remitting type.
• Patients will be included based on MR evidence of disease activity after Gadolinium (enhanced lesion) on a previous screening MR in the previous 3 weeks days before Feraheme administration.

You may not qualify if:

• Children (age \< 18)
• Those who lack decision-making capability
• Contraindication to MRI such as pacemaker, other MR-incompatible metal implants or claustrophobia
• Known allergy to dextran or drugs containing iron salts or any previous history of severe allergic reactions
• Evidence of iron overload such as hemochromatosis or other hematologic disorders that imply iron level superior to the normal level.
• Pregnancy or breast feeding.
• History of renal disease or estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) \<40ml/min/1.73m?

Sponsors & Collaborators

• Stanford University: lead

Study Sites (2)

Richard M. Lucas Center for Imaging (of Stanford University)

Stanford, California, 94304, United States

Location

Stanford Hospitals and Clinics

Stanford, California, 94305, United States

Location

Related Publications (15)

• Dousset V, Brochet B, Deloire MS, Lagoarde L, Barroso B, Caille JM, Petry KG. MR imaging of relapsing multiple sclerosis patients using ultra-small-particle iron oxide and compared with gadolinium. AJNR Am J Neuroradiol. 2006 May;27(5):1000-5.

  PMID: 16687532 BACKGROUND

• Vellinga MM, Oude Engberink RD, Seewann A, Pouwels PJ, Wattjes MP, van der Pol SM, Pering C, Polman CH, de Vries HE, Geurts JJ, Barkhof F. Pluriformity of inflammation in multiple sclerosis shown by ultra-small iron oxide particle enhancement. Brain. 2008 Mar;131(Pt 3):800-7. doi: 10.1093/brain/awn009. Epub 2008 Feb 1.

  PMID: 18245785 BACKGROUND

• Tourdias T, Roggerone S, Filippi M, Kanagaki M, Rovaris M, Miller DH, Petry KG, Brochet B, Pruvo JP, Radue EW, Dousset V. Assessment of disease activity in multiple sclerosis phenotypes with combined gadolinium- and superparamagnetic iron oxide-enhanced MR imaging. Radiology. 2012 Jul;264(1):225-33. doi: 10.1148/radiol.12111416.

  PMID: 22723563 BACKGROUND

• Daldrup-Link HE, Rydland J, Helbich TH, Bjornerud A, Turetschek K, Kvistad KA, Kaindl E, Link TM, Staudacher K, Shames D, Brasch RC, Haraldseth O, Rummeny EJ. Quantification of breast tumor microvascular permeability with feruglose-enhanced MR imaging: initial phase II multicenter trial. Radiology. 2003 Dec;229(3):885-92. doi: 10.1148/radiol.2293021045. Epub 2003 Oct 23.

  PMID: 14576446 BACKGROUND

• Metz S, Lohr S, Settles M, Beer A, Woertler K, Rummeny EJ, Daldrup-Link HE. Ferumoxtran-10-enhanced MR imaging of the bone marrow before and after conditioning therapy in patients with non-Hodgkin lymphomas. Eur Radiol. 2006 Mar;16(3):598-607. doi: 10.1007/s00330-005-0045-9. Epub 2005 Nov 12.

  PMID: 16284770 BACKGROUND

• Pai AB, Nielsen JC, Kausz A, Miller P, Owen JS. Plasma pharmacokinetics of two consecutive doses of ferumoxytol in healthy subjects. Clin Pharmacol Ther. 2010 Aug;88(2):237-42. doi: 10.1038/clpt.2010.80. Epub 2010 Jun 30.

  PMID: 20592725 BACKGROUND

• Provenzano R, Schiller B, Rao M, Coyne D, Brenner L, Pereira BJ. Ferumoxytol as an intravenous iron replacement therapy in hemodialysis patients. Clin J Am Soc Nephrol. 2009 Feb;4(2):386-93. doi: 10.2215/CJN.02840608. Epub 2009 Jan 28.

  PMID: 19176796 BACKGROUND

• Schwenk MH. Ferumoxytol: a new intravenous iron preparation for the treatment of iron deficiency anemia in patients with chronic kidney disease. Pharmacotherapy. 2010 Jan;30(1):70-9. doi: 10.1592/phco.30.1.70.

  PMID: 20030475 BACKGROUND

• Lu M, Cohen MH, Rieves D, Pazdur R. FDA report: Ferumoxytol for intravenous iron therapy in adult patients with chronic kidney disease. Am J Hematol. 2010 May;85(5):315-9. doi: 10.1002/ajh.21656.

  PMID: 20201089 BACKGROUND

• Dousset V, Delalande C, Ballarino L, Quesson B, Seilhan D, Coussemacq M, Thiaudiere E, Brochet B, Canioni P, Caille JM. In vivo macrophage activity imaging in the central nervous system detected by magnetic resonance. Magn Reson Med. 1999 Feb;41(2):329-33. doi: 10.1002/(sici)1522-2594(199902)41:23.0.co;2-z.

  PMID: 10080281 BACKGROUND

• Dousset V, Ballarino L, Delalande C, Coussemacq M, Canioni P, Petry KG, Caille JM. Comparison of ultrasmall particles of iron oxide (USPIO)-enhanced T2-weighted, conventional T2-weighted, and gadolinium-enhanced T1-weighted MR images in rats with experimental autoimmune encephalomyelitis. AJNR Am J Neuroradiol. 1999 Feb;20(2):223-7.

  PMID: 10094342 BACKGROUND

• Floris S, Blezer EL, Schreibelt G, Dopp E, van der Pol SM, Schadee-Eestermans IL, Nicolay K, Dijkstra CD, de Vries HE. Blood-brain barrier permeability and monocyte infiltration in experimental allergic encephalomyelitis: a quantitative MRI study. Brain. 2004 Mar;127(Pt 3):616-27. doi: 10.1093/brain/awh068. Epub 2003 Dec 22.

  PMID: 14691063 BACKGROUND

• Ladewig G, Jestaedt L, Misselwitz B, Solymosi L, Toyka K, Bendszus M, Stoll G. Spatial diversity of blood-brain barrier alteration and macrophage invasion in experimental autoimmune encephalomyelitis: a comparative MRI study. Exp Neurol. 2009 Nov;220(1):207-11. doi: 10.1016/j.expneurol.2009.08.027. Epub 2009 Sep 4.

  PMID: 19733560 BACKGROUND

• Chin CL, Pai M, Bousquet PF, Schwartz AJ, O'Connor EM, Nelson CM, Hradil VP, Cox BF, McRae BL, Fox GB. Distinct spatiotemporal pattern of CNS lesions revealed by USPIO-enhanced MRI in MOG-induced EAE rats implicates the involvement of spino-olivocerebellar pathways. J Neuroimmunol. 2009 Jun 25;211(1-2):49-55. doi: 10.1016/j.jneuroim.2009.03.012. Epub 2009 Apr 5.

  PMID: 19346009 BACKGROUND

• Petry KG, Boiziau C, Dousset V, Brochet B. Magnetic resonance imaging of human brain macrophage infiltration. Neurotherapeutics. 2007 Jul;4(3):434-42. doi: 10.1016/j.nurt.2007.05.005.

  PMID: 17599709 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Ferrosoferric Oxide; Gadolinium

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ferric Compounds; Iron Compounds; Inorganic Chemicals; Ferrous Compounds; Minerals; Lanthanoid Series Elements; Metals, Rare Earth; Elements; Metals

Study Officials

• Michael Zeineh, MD, PhD

  Stanford University

  STUDY DIRECTOR

• Brian Rutt, PhD

  Stanford University

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Protocol Director

Study Record Dates

• First Submitted: October 16, 2013
• First Posted: October 31, 2013
• Study Start: April 1, 2014
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: September 10, 2018

Record last verified: 2018-09

Locations

US (2)