Clinical trial NCT01718015: Neurotrophic Factors in Cerebrospinal Fluid in Diabetic Patients With Polyneuropathy
Official title: Neurotrophic Factors in Cerebrospinal Fluid in Diabetic Patients With Polyneuropathy
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Insulin-like Growth Factor I
Insulin-like Growth Factor II
Diabetes Complications
Polyneuropathies
Nerve Growth Factors
Keywords: Vascular Endothelial Growth Factor
Brain-Derived Neurothropic Factor
Diabetes Mellitus
CD-163
Cerebrospinal fluid
Peripheral Nervous System Diseases
Mass spectrometry
Lead sponsor: Aarhus University Hospital
Sponsor class: OTHER
Collaborators: name: Laboratory for Proteome Analysis and Protein Characterization, Aarhus University
First posted: 2012-10-31
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients who have performed a lumbar puncture at Department of Neurology and Department of Clinical Medicine (Endocrinology and Diabetes) Aarhus University Hospital, Denmark.

Brief summary: Background: The pathogenetic factors underlying development of diabetic polyneuropathy (DP) remain unclear. Reduced neurotrophic stimulation has been proposed as a possible mechanism. The neurotrophic factors IGF I and II, sCD-163, NGF, VEGF and BDNF are essential for development and regeneration of the nervous system. In earlier studies reduced concentrations of IGF-I and II in blood and reduced concentrations of NGF and BDNF in muscle and skin biopsies have been found in patients with DP.

Purpose: Our purpose is to determine the concentration and biological activity of Insulin-like Growth Factor I and II (IGF-I and II), soluble Cluster of Differentiation 163 (sCD-163), Nerve Growth Factor (NGF), Vascular Endothelial Growth Factor (VEGF) and Brain-derived Neurotropic Factor (BDNF) in cerebrospinal fluid and in blood in patients with diabetes and/or nerve disease (especially diabetic polyneuropathy) as well as in healthy control subjects. We will furthermore relate the findings to peripheral nerve function. In addition the composition of the cerebrospinal fluid will be analyzed using mass spectrometry.

Hypothesis: We hypothesize that DP develops due to reduced concentration and biological activity of neurotrophic factors. We expect the concentration of IGF-I and II, VEGF, NGF and BDNF to be reduced in cerebrospinal fluid in patients with DP compared to diabetic patients without damage to the nervous system and healthy control subjects.

Methods: Study subjects consists of patients from Department of Neurology and Department of Department of Clinical Medicine (Endocrinology and Diabetes) Aarhus University Hospital, Denmark, who are having a lumbar puncture performed.


Eligibility criteria: Inclusion Criteria:

* Patients with diabetic polyneuropathy
* Patients with diabetes without peripheral nerve disorder
* Patients with polyneuropathies not due to diabetes
* Patients not suffering from diabetes or nerve disease (control subjects)
* Patients with unspecified nerve disease

Exclusion Criteria:

* Other causes to the development of polyneuropathy in patients with diabetic polyneuropathy
* Cerebral infections

Primary outcomes:
measure: Concentrations of IGF-I and II, sCD-163, VEGF, NGF and BDNF in cerebrospinal fluid and blood.
timeFrame: november 2012 - august 2013
Secondary outcomes:
measure: Clinical neurological examination including tendon reflexes, muscle strength and sensation.
timeFrame: november 2012 - august 2013
measure: Isokinetic dynamometry (ankle and knee at non-dominating lower extremity, elbow and wrist at dominating upper extremity)
timeFrame: november 2012 - august 2013
measure: Vibration and temperature thresholds (index finger on dominating arm and great toe on non-dominating leg)
timeFrame: november 2012 - august 2013
measure: Nerve conduction studies: Nerve velocity, Amplitude, F-waves, Motor Unit Number Estimate (dominating arm and non-dominating leg)
timeFrame: November 2012 - august 2013
Other outcomes:
measure: Protein profile of the cerebrospinal fluid using mass spectrometry.
timeFrame: November 2012 - august 2013
Locations:
city: Aarhus
country: Denmark
facility: Department of Neurology, Aarhus University Hospital
Study officials:
References:
citation: Andreassen CS, Jakobsen J, Flyvbjerg A, Andersen H. Expression of neurotrophic factors in diabetic muscle--relation to neuropathy and muscle strength. Brain. 2009 Oct;132(Pt 10):2724-33. doi: 10.1093/brain/awp208. Epub 2009 Aug 20.
citation: Andersen H. Motor dysfunction in diabetes. Diabetes Metab Res Rev. 2012 Feb;28 Suppl 1:89-92. doi: 10.1002/dmrr.2257.
citation: Dyck PJ, Albers JW, Andersen H, Arezzo JC, Biessels GJ, Bril V, Feldman EL, Litchy WJ, O'Brien PC, Russell JW; Toronto Expert Panel on Diabetic Neuropathy. Diabetic polyneuropathies: update on research definition, diagnostic criteria and estimation of severity. Diabetes Metab Res Rev. 2011 Oct;27(7):620-8. doi: 10.1002/dmrr.1226.