sCD163 & CD19 as Candidate Biomarkers in CIDP and MMN

NCT02271724 | Unknown DMC

• 2 other identifiers: CIDP CD1631-10-72-300-14
• Study Type: observational
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) are characterized by progressive deterioration in muscle strength, loss of sensibility, diminished or absent reflexes and impaired fine motor control. Often it is caused by demyelination which is suitable for treatment but damage to the axons may also occur especially in case of insufficient treatment. CIDP and MMN are immune mediated neuropathies in which first choice of treatment is intravenous immunoglobulin (IVIG), although the mechanisms underlying the effect of the IVIG is not yet clarified. The patients are diagnosed by electrophysiological examination and elevated level of protein in the cerebrospinal fluid. The diagnosis may be difficult to make due to great clinical variation and insensitive examinations methods including lack of biomarkers. The purpose of this study is to define if patients treated with SCIG and IVIG for CIDP and MMN have higher concentrations of sCD163 and CD19 in their cerebrospinal fluid and serum compared with symptomatic control subjects and is related to disease severity. Furthermore it is to define if patients newly diagnosed with CIDP or MMN have higher levels of sCD163 and CD19, than patients treated regularly with SCIG and IVIG.

Conditions

Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Keywords

CIDP; MMN; Spinal fluid; CD163; CD19

Outcome Measures

Primary Outcomes (1)

• Concentrations of sCD-163 and CD19 in patients with CIDP and MMN.

  Day 1

Secondary Outcomes (1)

• Concentration of sCD163 and CD19 in newly diagnosed compared with established CIDP and MMN

  Day 1

Study Arms (4)

CIDP/MMN newly diagnosed (drug naive)

Patients, who are suspected to suffer from CIDP or MMN, will undergo a lumbar puncture as a part of the diagnostic procedure. We expect to include 5-10 patients. Lumbar puncture Blood sample

Procedure: Lumbar puncture; Procedure: Blood sample

CIDP/MMN treated

All patients with established CIDP in maintenance treatment with SCIG or IVIG are recruited from local registries at the outpatient clinic at Department of Neurology, Aarhus University Hospital. We expect that 10-15 patients with CIDP and MMN treated with SCIG or IVIG eligible for inclusion. Furthermore, we expect to include 10 CIDP and MMN patients in maintenance therapy from the outpatient clinics at Department of Neurology, Odense University Hospital and Department of Neurology, Aalborg University Hospital.

Procedure: Lumbar puncture; Procedure: Blood sample

Other peripheral neuropathies

Patients who are diagnosed with other causes of peripheral neuropathies than CIDP. We expect to include 20 patients

Procedure: Lumbar puncture; Procedure: Blood sample

Syptomatic controls

Controls include patients with unspecified neurological symptoms or diseases who will undergo a lumbar puncture at the Department of Neurology at Aarhus University Hospital as part of their diagnostic work up irrespective of this study plus healthy controls. We expected to include 40-50 symptomatic controls

Procedure: Lumbar puncture; Procedure: Blood sample

Interventions

Lumbar puncture PROCEDURE

Lumbar puncture for spinal fluid

Also known as: Spinal tap

CIDP/MMN newly diagnosed (drug naive); CIDP/MMN treated; Other peripheral neuropathies; Syptomatic controls

Blood sample PROCEDURE

Blood sample

CIDP/MMN newly diagnosed (drug naive); CIDP/MMN treated; Other peripheral neuropathies; Syptomatic controls

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

* Patients with CIDP and MMN in maintenance treatment with SCIG or IVIG * Patients with newly diagnosed CIDP and MMN (drug-naïve) * Patients with other causes of peripheral neuropathies * Symptomatic controls

You may qualify if:

• Patients diagnosed with CIDP or MMN or patients suspected to have CIDP or MMN
• Controls:
• Age \>18 years

You may not qualify if:

• \<18 years
• Acute infections including neuroinfection
• Diabetes
• Other disorders known to have elevated levels of sCD163 and CD19
• Disorders or treatments that contraindicate a lumbar puncture.

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Department of Neurology, Aarhus University Hospital

Aarhus C, 8000, Denmark

RECRUITING

Related Publications (17)

• Bohn AB, Nederby L, Harbo T, Skovbo A, Vorup-Jensen T, Krog J, Jakobsen J, Hokland ME. The effect of IgG levels on the number of natural killer cells and their Fc receptors in chronic inflammatory demyelinating polyradiculoneuropathy. Eur J Neurol. 2011 Jun;18(6):919-24. doi: 10.1111/j.1468-1331.2010.03333.x. Epub 2011 Jan 11.

  PMID: 21219545 BACKGROUND

• Markvardsen LH, Debost JC, Harbo T, Sindrup SH, Andersen H, Christiansen I, Otto M, Olsen NK, Lassen LL, Jakobsen J; Danish CIDP and MMN Study Group. Subcutaneous immunoglobulin in responders to intravenous therapy with chronic inflammatory demyelinating polyradiculoneuropathy. Eur J Neurol. 2013 May;20(5):836-42. doi: 10.1111/ene.12080. Epub 2013 Jan 7.

  PMID: 23294032 BACKGROUND

• Harbo T, Andersen H, Hess A, Hansen K, Sindrup SH, Jakobsen J. Subcutaneous versus intravenous immunoglobulin in multifocal motor neuropathy: a randomized, single-blinded cross-over trial. Eur J Neurol. 2009 May;16(5):631-8. doi: 10.1111/j.1468-1331.2009.02568.x. Epub 2009 Feb 19.

  PMID: 19236457 BACKGROUND

• Van den Bergh PY, Pieret F. Electrodiagnostic criteria for acute and chronic inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve. 2004 Apr;29(4):565-74. doi: 10.1002/mus.20022.

  PMID: 15052622 BACKGROUND

• Harbo T, Andersen H, Jakobsen J. Acute motor response following a single IVIG treatment course in chronic inflammatory demyelinating polyneuropathy. Muscle Nerve. 2009 Apr;39(4):439-47. doi: 10.1002/mus.21305.

  PMID: 19229876 BACKGROUND

• Markvardsen LH, Jakobsen J. [Exfoliative dermatitis as a side effect of intravenous immunoglobulin treatment]. Ugeskr Laeger. 2011 Oct 24;173(43):2725-6. Danish.

  PMID: 22027232 BACKGROUND

• Markvardsen LH, Christiansen I, Harbo T, Jakobsen J. Hemolytic anemia following high dose intravenous immunoglobulin in patients with chronic neurological disorders. Eur J Neurol. 2014;21(1):147-52. doi: 10.1111/ene.12287. Epub 2013 Nov 4.

  PMID: 24180709 BACKGROUND

• Fuglsang-Frederiksen A, Pugdahl K. Current status on electrodiagnostic standards and guidelines in neuromuscular disorders. Clin Neurophysiol. 2011 Mar;122(3):440-455. doi: 10.1016/j.clinph.2010.06.025. Epub 2010 Jul 31.

  PMID: 20673740 BACKGROUND

• Rentzos M, Angeli AV, Rombos A, Kyrozis A, Nikolaou C, Zouvelou V, Dimitriou A, Zoga M, Evangelopoulos ME, Tsatsi A, Tsoutsou A, Evdokimidis I. Proinflammatory cytokines in serum and cerebrospinal fluid of CIDP patients. Neurol Res. 2012 Nov;34(9):842-6. doi: 10.1179/1743132812Y.0000000074. Epub 2012 Sep 4.

  PMID: 22947427 BACKGROUND

• Stubgen JP. A review of the use of biological agents for chronic inflammatory demyelinating polyradiculoneuropathy. J Neurol Sci. 2013 Mar 15;326(1-2):1-9. doi: 10.1016/j.jns.2013.01.003. Epub 2013 Jan 19.

  PMID: 23337197 BACKGROUND

• Sommer C, Toyka K. Nerve biopsy in chronic inflammatory neuropathies: in situ biomarkers. J Peripher Nerv Syst. 2011 Jun;16 Suppl 1:24-9. doi: 10.1111/j.1529-8027.2011.00301.x.

  PMID: 21696493 BACKGROUND

• Zhang HL, Zhang XM, Mao XJ, Deng H, Li HF, Press R, Fredrikson S, Zhu J. Altered cerebrospinal fluid index of prealbumin, fibrinogen, and haptoglobin in patients with Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy. Acta Neurol Scand. 2012 Feb;125(2):129-35. doi: 10.1111/j.1600-0404.2011.01511.x. Epub 2011 Mar 24.

  PMID: 21434877 BACKGROUND

• Kjaergaard AG, Rodgaard-Hansen S, Dige A, Krog J, Moller HJ, Tonnesen E. Monocyte expression and soluble levels of the haemoglobin receptor (CD163/sCD163) and the mannose receptor (MR/sMR) in septic and critically ill non-septic ICU patients. PLoS One. 2014 Mar 17;9(3):e92331. doi: 10.1371/journal.pone.0092331. eCollection 2014.

  PMID: 24637679 BACKGROUND

• Etzerodt A, Moestrup SK. CD163 and inflammation: biological, diagnostic, and therapeutic aspects. Antioxid Redox Signal. 2013 Jun 10;18(17):2352-63. doi: 10.1089/ars.2012.4834. Epub 2012 Oct 19.

  PMID: 22900885 BACKGROUND

• Moller HJ. Soluble CD163. Scand J Clin Lab Invest. 2012 Feb;72(1):1-13. doi: 10.3109/00365513.2011.626868. Epub 2011 Nov 7.

  PMID: 22060747 BACKGROUND

• Abraham PM, Quan SH, Dukala D, Soliven B. CD19 as a therapeutic target in a spontaneous autoimmune polyneuropathy. Clin Exp Immunol. 2014 Feb;175(2):181-91. doi: 10.1111/cei.12215.

  PMID: 24116957 BACKGROUND

• Korporal-Kuhnke M, Haas J, Schwarz A, Jarius S, Wildemann B. Plasmacytosis is a common immune signature in patients with MMN and CIDP and responds to treatment with IVIg. J Neuroimmunol. 2015 Jan 15;278:60-8. doi: 10.1016/j.jneuroim.2014.11.012. Epub 2014 Nov 22.

  PMID: 25595253 BACKGROUND

Related Links

• Chronic inflammatory demyelinating polyneuropathy: Etiology, clinical features, and diagnosis

Biospecimen

Retention: SAMPLES WITHOUT DNA

Spinal fluid and blood sample for identification of different factors

MeSH Terms

Conditions

Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Interventions

Spinal Puncture; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Polyradiculoneuropathy; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biopsy; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Henning Andersen, Professor

  Department of Neurology, Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Malalai Musleh, Student

CONTACT

+45 27134658; malalaimusleh@hotmail.com

Henning Andersen, Professor

CONTACT

+45 78463281; hennande@rm.dk

Study Design

• Study Type: observational
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2014
• First Posted: October 22, 2014
• Study Start: September 1, 2015
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: May 16, 2016

Record last verified: 2015-09

Locations

DK (1)