<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01718015</url>
  </required_header>
  <id_info>
    <org_study_id>1-10-72-470-12.</org_study_id>
    <secondary_id>1-16-02-272-12</secondary_id>
    <nct_id>NCT01718015</nct_id>
  </id_info>
  <brief_title>Neurotrophic Factors in Cerebrospinal Fluid in Diabetic Patients With Polyneuropathy</brief_title>
  <official_title>Neurotrophic Factors in Cerebrospinal Fluid in Diabetic Patients With Polyneuropathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aarhus University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Laboratory for Proteome Analysis and Protein Characterization, Aarhus University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Aarhus University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background: The pathogenetic factors underlying development of diabetic polyneuropathy (DP)&#xD;
      remain unclear. Reduced neurotrophic stimulation has been proposed as a possible mechanism.&#xD;
      The neurotrophic factors IGF I and II, sCD-163, NGF, VEGF and BDNF are essential for&#xD;
      development and regeneration of the nervous system. In earlier studies reduced concentrations&#xD;
      of IGF-I and II in blood and reduced concentrations of NGF and BDNF in muscle and skin&#xD;
      biopsies have been found in patients with DP.&#xD;
&#xD;
      Purpose: Our purpose is to determine the concentration and biological activity of&#xD;
      Insulin-like Growth Factor I and II (IGF-I and II), soluble Cluster of Differentiation 163&#xD;
      (sCD-163), Nerve Growth Factor (NGF), Vascular Endothelial Growth Factor (VEGF) and&#xD;
      Brain-derived Neurotropic Factor (BDNF) in cerebrospinal fluid and in blood in patients with&#xD;
      diabetes and/or nerve disease (especially diabetic polyneuropathy) as well as in healthy&#xD;
      control subjects. We will furthermore relate the findings to peripheral nerve function. In&#xD;
      addition the composition of the cerebrospinal fluid will be analyzed using mass spectrometry.&#xD;
&#xD;
      Hypothesis: We hypothesize that DP develops due to reduced concentration and biological&#xD;
      activity of neurotrophic factors. We expect the concentration of IGF-I and II, VEGF, NGF and&#xD;
      BDNF to be reduced in cerebrospinal fluid in patients with DP compared to diabetic patients&#xD;
      without damage to the nervous system and healthy control subjects.&#xD;
&#xD;
      Methods: Study subjects consists of patients from Department of Neurology and Department of&#xD;
      Department of Clinical Medicine (Endocrinology and Diabetes) Aarhus University Hospital,&#xD;
      Denmark, who are having a lumbar puncture performed.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>November 2012</start_date>
  <completion_date type="Anticipated">August 2013</completion_date>
  <primary_completion_date type="Anticipated">August 2013</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Concentrations of IGF-I and II, sCD-163, VEGF, NGF and BDNF in cerebrospinal fluid and blood.</measure>
    <time_frame>november 2012 - august 2013</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical neurological examination including tendon reflexes, muscle strength and sensation.</measure>
    <time_frame>november 2012 - august 2013</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Isokinetic dynamometry (ankle and knee at non-dominating lower extremity, elbow and wrist at dominating upper extremity)</measure>
    <time_frame>november 2012 - august 2013</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vibration and temperature thresholds (index finger on dominating arm and great toe on non-dominating leg)</measure>
    <time_frame>november 2012 - august 2013</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nerve conduction studies: Nerve velocity, Amplitude, F-waves, Motor Unit Number Estimate (dominating arm and non-dominating leg)</measure>
    <time_frame>November 2012 - august 2013</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Protein profile of the cerebrospinal fluid using mass spectrometry.</measure>
    <time_frame>November 2012 - august 2013</time_frame>
  </other_outcome>
  <number_of_groups>5</number_of_groups>
  <enrollment type="Anticipated">70</enrollment>
  <condition>Insulin-like Growth Factor I</condition>
  <condition>Insulin-like Growth Factor II</condition>
  <condition>Diabetes Complications</condition>
  <condition>Polyneuropathies</condition>
  <condition>Nerve Growth Factors</condition>
  <arm_group>
    <arm_group_label>Patients with diabetic polyneuropathy</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients with diabetes without peripheral nerve disorder</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients with polyneuropathies not due to diabetes</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients not suffering from diabetes or nerve disease</arm_group_label>
    <description>Control subjects</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients with unspecified nerve disease</arm_group_label>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Cerebrospinal fluid, plasma and serum&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients who have performed a lumbar puncture at Department of Neurology and Department of&#xD;
        Clinical Medicine (Endocrinology and Diabetes) Aarhus University Hospital, Denmark.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with diabetic polyneuropathy&#xD;
&#xD;
          -  Patients with diabetes without peripheral nerve disorder&#xD;
&#xD;
          -  Patients with polyneuropathies not due to diabetes&#xD;
&#xD;
          -  Patients not suffering from diabetes or nerve disease (control subjects)&#xD;
&#xD;
          -  Patients with unspecified nerve disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Other causes to the development of polyneuropathy in patients with diabetic&#xD;
             polyneuropathy&#xD;
&#xD;
          -  Cerebral infections&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Mia Jørgensen, medical research year student</last_name>
    <phone>9194 4232</phone>
    <phone_ext>+45</phone_ext>
    <email>mia.jorgensen@studmed.au.dk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Department of Neurology, Aarhus University Hospital</name>
      <address>
        <city>Aarhus</city>
        <zip>8000</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <contact>
      <last_name>Henning Andersen, Professor, MD Phd</last_name>
      <email>hennande@rm.dk</email>
    </contact>
    <investigator>
      <last_name>Henning Andersen, Professor, MD Phd</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <reference>
    <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>
    <PMID>19696031</PMID>
  </reference>
  <reference>
    <citation>Andersen H. Motor dysfunction in diabetes. Diabetes Metab Res Rev. 2012 Feb;28 Suppl 1:89-92. doi: 10.1002/dmrr.2257.</citation>
    <PMID>22271730</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>21695763</PMID>
  </reference>
  <verification_date>October 2012</verification_date>
  <study_first_submitted>October 29, 2012</study_first_submitted>
  <study_first_submitted_qc>October 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 31, 2012</study_first_posted>
  <last_update_submitted>October 29, 2012</last_update_submitted>
  <last_update_submitted_qc>October 29, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 31, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Aarhus University Hospital</investigator_affiliation>
    <investigator_full_name>Mia Jørgensen</investigator_full_name>
    <investigator_title>Medical Research Year Student</investigator_title>
  </responsible_party>
  <keyword>Vascular Endothelial Growth Factor</keyword>
  <keyword>Brain-Derived Neurothropic Factor</keyword>
  <keyword>Diabetes Mellitus</keyword>
  <keyword>CD-163</keyword>
  <keyword>Cerebrospinal fluid</keyword>
  <keyword>Peripheral Nervous System Diseases</keyword>
  <keyword>Mass spectrometry</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polyneuropathies</mesh_term>
    <mesh_term>Diabetes Complications</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01718015
org study id: 1-10-72-470-12.
secondary id: 1-16-02-272-12
nct id: NCT01718015
lead sponsor: 
collaborator: 
has dmc: Yes
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.
observational model: Case-Only
time perspective: Prospective
measure: Concentrations of IGF-I and II, sCD-163, VEGF, NGF and BDNF in cerebrospinal fluid and blood.
time frame: november 2012 - august 2013
measure: Clinical neurological examination including tendon reflexes, muscle strength and sensation.
time frame: november 2012 - august 2013
measure: Isokinetic dynamometry (ankle and knee at non-dominating lower extremity, elbow and wrist at dominating upper extremity)
time frame: november 2012 - august 2013
measure: Vibration and temperature thresholds (index finger on dominating arm and great toe on non-dominating leg)
time frame: november 2012 - august 2013
measure: Nerve conduction studies: Nerve velocity, Amplitude, F-waves, Motor Unit Number Estimate (dominating arm and non-dominating leg)
time frame: November 2012 - august 2013
measure: Protein profile of the cerebrospinal fluid using mass spectrometry.
time frame: November 2012 - august 2013
arm group label: Patients with diabetic polyneuropathy
arm group label: Patients with diabetes without peripheral nerve disorder
arm group label: Patients with polyneuropathies not due to diabetes
arm group label: Patients not suffering from diabetes or nerve disease
description: Control subjects
arm group label: Patients with unspecified nerve disease
Cerebrospinal fluid, plasma and serum
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mia Jørgensen, medical research year student
phone: 9194 4232
phone ext: +45
email: mia.jorgensen@studmed.au.dk
facility: 
contact: 
investigator: 
country: Denmark
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.
PMID: 19696031
citation: Andersen H. Motor dysfunction in diabetes. Diabetes Metab Res Rev. 2012 Feb;28 Suppl 1:89-92. doi: 10.1002/dmrr.2257.
PMID: 22271730
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.
PMID: 21695763
responsible party type: Principal Investigator
investigator affiliation: Aarhus University Hospital
investigator full name: Mia Jørgensen
investigator title: Medical Research Year Student
mesh term: Polyneuropathies
mesh term: Diabetes Complications