xml: <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/NCT05984771</url>
    </required_header>
    <id_info>
      <org_study_id>54230/12.12.2020</org_study_id>
      <nct_id>NCT05984771</nct_id>
    </id_info>
    <brief_title>Efficacy and Safety of the Combination of Ten Elements for 6 Months in Patients With Diabetic Neuropathy : A Pilot Study</brief_title>
    <official_title>Efficacy and Safety of the Combination of Superoxide Dismutase, Alpha Lipoic Acid, Vitamins B12, B1, B2, B6, E, Mg, Zn and Palmitoylethanolamide for 6 Months in Patients With Diabetic Neuropathy : A Pilot Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Aristotle University Of Thessaloniki</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Aristotle University Of Thessaloniki</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        To investigate the efficacy of Superoxide Dismutase (SOD, 70 UI), Palmitoylethanolamide (PEA,&#xD;
        300 mg) Alpha Lipoic Acid (ALA, 300 mg), vitamins B6 (1.5 mg), B1 (1.1 mg), B12 (2.5 mcg), E&#xD;
        (7.5 mg), Nicotinamide (9 mg) and minerals (Mg 30 mg, Zn 2,5 mg) in one tablet in patients&#xD;
        with Diabetic Neuropathy (DN).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        To investigate the efficacy of Superoxide Dismutase (SOD, 70 UI), Palmitoylethanolamide (PEA,&#xD;
        300 mg) Alpha Lipoic Acid (ALA, 300 mg), vitamins B6 (1.5 mg), B1 (1.1 mg), B12 (2.5 mcg), E&#xD;
        (7.5 mg), Nicotinamide (9 mg) and minerals (Mg 30 mg, Zn 2,5 mg) in one tablet in patients&#xD;
        with Diabetic Neuropathy (DN).&#xD;
  &#xD;
        Patients - methods: In this pilot study, 61 patients with Diabetes Mellitus Type 2 (DMT2, 31&#xD;
        women), with mean duration of DM 17.5 years and mean age 63 years were randomly assigned,&#xD;
        either to receive the combination of ten elements (2 tablets/24h) in the active group,&#xD;
        (n=30), or the placebo (n=31) for 6 months. We used Michigan Neuropathy Screening Instrument&#xD;
        Questionnaire and Examination (MNSIQ and MNSIE), measured vibration perception threshold&#xD;
        (VPT) and Cardiovascular Autonomic Reflex Tests (CARTs). Nerve function was assessed by DPN&#xD;
        Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. Sudomotor function was&#xD;
        assessed with SUDOSCAN that measures electrochemical skin conductance in hands and feet (ESCH&#xD;
        and ESCF). Pain (PS) questionnaire was administered, also. All patients received metformin&#xD;
        for at least 4 years.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">January 10, 2021</start_date>
    <completion_date type="Actual">June 30, 2022</completion_date>
    <primary_completion_date type="Actual">June 30, 2022</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>pilot study</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <masking_description>The investigator and examiner did not know the type of drug provided</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Nerve conduction study to measure the velocity of the nerve impulse in the sural nerve</measure>
      <time_frame>6 months</time_frame>
      <description>Measurement of nerve conduction velocity with Neurometrix Diabetic Peripheral Neuropathy scan device</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Measurement of individual Vibration Perception Threshold to study vibration perception in the feet</measure>
      <time_frame>6 months</time_frame>
      <description>Measurement of vibration perception threshold with Biothesiometer</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Michigan Screening Neuropathy Questionnaire and Examination</measure>
      <time_frame>6 months</time_frame>
      <description>use of michigan screening questionnaire and examination</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Measurement of electrochemical skin conductance</measure>
      <time_frame>6 months</time_frame>
      <description>measurement with Sudoscan the electrochemical skin conductance in hands and feet</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Glycated Hemoglobin</measure>
      <time_frame>6 months</time_frame>
      <description>Measurement of Glycated Hemoglobin</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>vitamin B12 levels</measure>
      <time_frame>6 months</time_frame>
      <description>measurement of B12 levels</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Actual">70</enrollment>
    <condition>Diabetic Neuropathies</condition>
    <condition>Diabetes Mellitus</condition>
    <condition>Dietary Supplement</condition>
    <arm_group>
      <arm_group_label>Active group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>10-element combination tablet (n=30) Superoxide Dismutase (SOD, 70 UI), Palmitoylethanolamide (PEA, 300 mg) Alpha Lipoic Acid (ALA, 300 mg), vitamins B6 (1.5 mg), B1 (1.1 mg), B12 (2.5 mcg), E (7.5 mg), Nicotinamide (9 mg) and minerals (Mg 30 mg, Zn 2,5 mg) in one tablet for 6 months</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>usual care</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Epineuron</intervention_name>
      <description>Superoxide Dismutase (SOD, 70 UI), Palmitoylethanolamide (PEA, 300 mg) Alpha Lipoic Acid (ALA, 300 mg), vitamins B6 (1.5 mg), B1 (1.1 mg), B12 (2.5 mcg), E (7.5 mg), Nicotinamide (9 mg) and minerals (Mg 30 mg, Zn 2,5 mg) in one tablet (Epineuron)</description>
      <arm_group_label>Active group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo group</intervention_name>
      <description>Usual care</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  on metformin therapy for at least 4 years&#xD;
  &#xD;
            -  diabetes mellitus type 2 with diabetic neuropathy&#xD;
  &#xD;
            -  painful neuropathy&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  healthy&#xD;
  &#xD;
            -  without diabetic neuropathy&#xD;
  &#xD;
            -  pregant&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>N/A</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>University General Hospital AHEPA</name>
        <address>
          <city>Thessaloníki</city>
          <state>Thessaloniki</state>
          <zip>54621</zip>
          <country>Greece</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Greece</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 26, 2023</study_first_submitted>
    <study_first_submitted_qc>August 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 8, 2023</last_update_submitted>
    <last_update_submitted_qc>August 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 9, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Aristotle University Of Thessaloniki</investigator_affiliation>
      <investigator_full_name>Prof. Triantafyllos Didangelos</investigator_full_name>
      <investigator_title>Professor of Internal Medicine and Diabetology</investigator_title>
    </responsible_party>
    <keyword>diabetes mellitus</keyword>
    <keyword>neuropathy</keyword>
    <keyword>pain</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Peripheral Nervous System Diseases</mesh_term>
      <mesh_term>Diabetic Neuropathies</mesh_term>
      <mesh_term>Diabetes Mellitus</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05984771
  org study id: 54230/12.12.2020
  nct id: NCT05984771
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  To investigate the efficacy of Superoxide Dismutase (SOD, 70 UI), Palmitoylethanolamide (PEA,
        300 mg) Alpha Lipoic Acid (ALA, 300 mg), vitamins B6 (1.5 mg), B1 (1.1 mg), B12 (2.5 mcg), E
        (7.5 mg), Nicotinamide (9 mg) and minerals (Mg 30 mg, Zn 2,5 mg) in one tablet in patients
        with Diabetic Neuropathy (DN).
  To investigate the efficacy of Superoxide Dismutase (SOD, 70 UI), Palmitoylethanolamide (PEA,
        300 mg) Alpha Lipoic Acid (ALA, 300 mg), vitamins B6 (1.5 mg), B1 (1.1 mg), B12 (2.5 mcg), E
        (7.5 mg), Nicotinamide (9 mg) and minerals (Mg 30 mg, Zn 2,5 mg) in one tablet in patients
        with Diabetic Neuropathy (DN).
  
        Patients - methods: In this pilot study, 61 patients with Diabetes Mellitus Type 2 (DMT2, 31
        women), with mean duration of DM 17.5 years and mean age 63 years were randomly assigned,
        either to receive the combination of ten elements (2 tablets/24h) in the active group,
        (n=30), or the placebo (n=31) for 6 months. We used Michigan Neuropathy Screening Instrument
        Questionnaire and Examination (MNSIQ and MNSIE), measured vibration perception threshold
        (VPT) and Cardiovascular Autonomic Reflex Tests (CARTs). Nerve function was assessed by DPN
        Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. Sudomotor function was
        assessed with SUDOSCAN that measures electrochemical skin conductance in hands and feet (ESCH
        and ESCF). Pain (PS) questionnaire was administered, also. All patients received metformin
        for at least 4 years.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: pilot study
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  masking description: The investigator and examiner did not know the type of drug provided
  measure: Nerve conduction study to measure the velocity of the nerve impulse in the sural nerve
  time frame: 6 months
  description: Measurement of nerve conduction velocity with Neurometrix Diabetic Peripheral Neuropathy scan device
  measure: Measurement of individual Vibration Perception Threshold to study vibration perception in the feet
  time frame: 6 months
  description: Measurement of vibration perception threshold with Biothesiometer
  measure: Michigan Screening Neuropathy Questionnaire and Examination
  time frame: 6 months
  description: use of michigan screening questionnaire and examination
  measure: Measurement of electrochemical skin conductance
  time frame: 6 months
  description: measurement with Sudoscan the electrochemical skin conductance in hands and feet
  measure: Glycated Hemoglobin
  time frame: 6 months
  description: Measurement of Glycated Hemoglobin
  measure: vitamin B12 levels
  time frame: 6 months
  description: measurement of B12 levels
  arm group label: Active group
  arm group type: Active Comparator
  description: 10-element combination tablet (n=30) Superoxide Dismutase (SOD, 70 UI), Palmitoylethanolamide (PEA, 300 mg) Alpha Lipoic Acid (ALA, 300 mg), vitamins B6 (1.5 mg), B1 (1.1 mg), B12 (2.5 mcg), E (7.5 mg), Nicotinamide (9 mg) and minerals (Mg 30 mg, Zn 2,5 mg) in one tablet for 6 months
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: usual care
  intervention type: Dietary Supplement
  intervention name: Epineuron
  description: Superoxide Dismutase (SOD, 70 UI), Palmitoylethanolamide (PEA, 300 mg) Alpha Lipoic Acid (ALA, 300 mg), vitamins B6 (1.5 mg), B1 (1.1 mg), B12 (2.5 mcg), E (7.5 mg), Nicotinamide (9 mg) and minerals (Mg 30 mg, Zn 2,5 mg) in one tablet (Epineuron)
  arm group label: Active group
  intervention type: Other
  intervention name: Placebo group
  description: Usual care
  arm group label: Placebo
  criteria: 
  gender: Female
  minimum age: N/A
  maximum age: N/A
  healthy volunteers: No
  facility: 
  country: Greece
  responsible party type: Principal Investigator
  investigator affiliation: Aristotle University Of Thessaloniki
  investigator full name: Prof. Triantafyllos Didangelos
  investigator title: Professor of Internal Medicine and Diabetology
  mesh term: Peripheral Nervous System Diseases
  mesh term: Diabetic Neuropathies
  mesh term: Diabetes Mellitus
  sharing ipd: No