<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/NCT03778580</url>
  </required_header>
  <id_info>
    <org_study_id>AAAR5451</org_study_id>
    <nct_id>NCT03778580</nct_id>
  </id_info>
  <brief_title>Advanced Glycation Endproducts and Bone Material Strength in T2D Treated With Pyridoxamine</brief_title>
  <official_title>Advanced Glycation Endproducts and Bone Material Strength in Type 2 Diabetes Treated With Pyridoxamine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Columbia University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Columbia University</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The purpose of this study is to determine if a specific form of Vitamin B known as&#xD;
      Pyridoxamine helps improve bone strength over one year in women (&gt;65 yrs old) with Type 2&#xD;
      Diabetes. The investigators know that people with type 2 diabetes have the lower bone&#xD;
      material strength and the investigators suspect this is due to high levels of circulating&#xD;
      sugars that build up over time (known as Advanced Glycation Endproducts). The investigators&#xD;
      will study whether using a specific form of vitamin B, known as pyridoxamine helps improve&#xD;
      bone strength and reduce levels of circulating sugars over a one year time period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Type 2 Diabetes Mellitus (T2DM) has become one of the most important diseases of our time.&#xD;
      Recent research shows that diabetes has negative effects on bones and that people with&#xD;
      diabetes might more likely to break a bone. The investigators don't know the reasons for&#xD;
      this, but the investigators suspect that normal bone replacement is slowed down in diabetes&#xD;
      and this could slow down the growth of new bone. It is possible that the normal material&#xD;
      becomes weaker because sugar-related components (&quot;Advanced Glycation Endproducts&quot;) are making&#xD;
      the bone more brittle. The investigators have shown in past research that people who have&#xD;
      type 2 diabetes are more likely to have both weaker bone with lower &quot;bone material strength&quot;&#xD;
      and also higher level of sugar-related components(&quot;Advanced Glycation Endproducts&quot;). This&#xD;
      study will focus on attempting to lower the sugar-related components(&quot;Advanced Glycation&#xD;
      Endproducts&quot;) by treating a group of patients with type 2 diabetes with an over- the- counter&#xD;
      B vitamin, known as vitamin B6 or pyridoxamine for one year. The investigators will compare&#xD;
      post-menopausal women both before and after pyridoxamine use and study them in terms of&#xD;
      different bone features based on blood tests, bone imaging, a bone indentation test and a&#xD;
      measurement of sugar-related components in the skin. This study will help to clarify if using&#xD;
      pyridoxamine helps improve bone strength in women with diabetes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2018</start_date>
  <completion_date type="Actual">February 28, 2022</completion_date>
  <primary_completion_date type="Actual">February 28, 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Bone formation in serum by P1NP</measure>
    <time_frame>12 months</time_frame>
    <description>change in serum biochemical marker of bone formation, P1NP</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Advanced glycation endproducts</measure>
    <time_frame>12 months</time_frame>
    <description>Skin assessment of advanced glycation endproducts</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">55</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>pyridoxamine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>pyridoxamine dihydrochloride (over- the- counter type of vitamin B6) 200 mg po bid for one year</description>
  </arm_group>
  <arm_group>
    <arm_group_label>identical placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>identical placebo po bid for one year</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Pyridoxamine Dihydrochloride</intervention_name>
    <description>pyridoxamine dihydrochloride (over- the- counter type of vitamin B6) 200 mg po bid</description>
    <arm_group_label>pyridoxamine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>placebo</description>
    <arm_group_label>identical placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Postmenopausal women ≥65 years&#xD;
&#xD;
          -  Diagnosis of T2D for ≥ 5 years, with all HbA1c levels.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hormone replacement treatment (HTR) use (to avoid the influence of estrogen).&#xD;
&#xD;
          -  Fractures (excluding skull, facial bones, metacarpals, fingers, toes, and fractures&#xD;
             associated with severe trauma) within 12 months.&#xD;
&#xD;
          -  A history of pathological fractures (eg, due to Paget's disease, myeloma, metastatic&#xD;
             malignancy).&#xD;
&#xD;
          -  Type 1 diabetes&#xD;
&#xD;
          -  Disorders associated with altered skeletal structure or function (chronic liver&#xD;
             disease' chronic renal disease stage 4 [eGFR &lt; 30 mL/mim/1.73 m2] or worse,&#xD;
             malignancy, hypoparathyroidism or hyperparathyroidism,acromegaly, Cushing's syndrome,&#xD;
             hypopituitarism, alcohol intake &gt; 3U/day).&#xD;
&#xD;
          -  Treatment with any of the following drugs in part year:current corticosteroid,&#xD;
             anticonvulsant therapy(phenytoin, phenobarbital, primidone, carbamazepine), SGLT2&#xD;
             inhibitor if on it for &lt; 1 year), pharmacological doses of thyroid hormone&#xD;
             (TSH&lt;normal), adrenal or anabolic steroids, Aromatase inhibitors, calcitonin,&#xD;
             bisphosphonates, denosumab, estrogen, or selective estrogen receptor modulator, sodium&#xD;
             fluoride, teriparatide, thiazolidinediones(TZDs).&#xD;
&#xD;
          -  Serum 25(OH)D levels &lt; 20 ng/ml. If 25(OH)D levels are &lt; 20 ng/ml, rescreening will be&#xD;
             allowed following a vitamin D loading regimen of 50,000 IU/week for 4 weeks. If serum&#xD;
             25(OH) D levels are ≥ 20 ng/ml after supplementation, the subject will be allowed to&#xD;
             enroll.&#xD;
&#xD;
          -  Current use of pyridoxamine (although not multivitamin or vitamin B6 users because&#xD;
             pyridoxamine is not at pharmacologic levels in these supplements).&#xD;
&#xD;
          -  Allergy to pyridoxamine and vitamin B6.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mishaela Rubin,, M.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Columbia University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Columbia University Medical Center - Harkness Pavillion</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>December 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 17, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>August 1, 2022</last_update_submitted>
  <last_update_submitted_qc>August 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Columbia University</investigator_affiliation>
    <investigator_full_name>Mishaela Rubin</investigator_full_name>
    <investigator_title>Associate Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Vitamin B6</keyword>
  <keyword>Diabetes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pyridoxamine</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 10, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/80/NCT03778580/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03778580
org study id: AAAR5451
nct id: NCT03778580
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to determine if a specific form of Vitamin B known as
      Pyridoxamine helps improve bone strength over one year in women (>65 yrs old) with Type 2
      Diabetes. The investigators know that people with type 2 diabetes have the lower bone
      material strength and the investigators suspect this is due to high levels of circulating
      sugars that build up over time (known as Advanced Glycation Endproducts). The investigators
      will study whether using a specific form of vitamin B, known as pyridoxamine helps improve
      bone strength and reduce levels of circulating sugars over a one year time period.
Type 2 Diabetes Mellitus (T2DM) has become one of the most important diseases of our time.
      Recent research shows that diabetes has negative effects on bones and that people with
      diabetes might more likely to break a bone. The investigators don't know the reasons for
      this, but the investigators suspect that normal bone replacement is slowed down in diabetes
      and this could slow down the growth of new bone. It is possible that the normal material
      becomes weaker because sugar-related components ("Advanced Glycation Endproducts") are making
      the bone more brittle. The investigators have shown in past research that people who have
      type 2 diabetes are more likely to have both weaker bone with lower "bone material strength"
      and also higher level of sugar-related components("Advanced Glycation Endproducts"). This
      study will focus on attempting to lower the sugar-related components("Advanced Glycation
      Endproducts") by treating a group of patients with type 2 diabetes with an over- the- counter
      B vitamin, known as vitamin B6 or pyridoxamine for one year. The investigators will compare
      post-menopausal women both before and after pyridoxamine use and study them in terms of
      different bone features based on blood tests, bone imaging, a bone indentation test and a
      measurement of sugar-related components in the skin. This study will help to clarify if using
      pyridoxamine helps improve bone strength in women with diabetes.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Bone formation in serum by P1NP
time frame: 12 months
description: change in serum biochemical marker of bone formation, P1NP
measure: Advanced glycation endproducts
time frame: 12 months
description: Skin assessment of advanced glycation endproducts
arm group label: pyridoxamine
arm group type: Experimental
description: pyridoxamine dihydrochloride (over- the- counter type of vitamin B6) 200 mg po bid for one year
arm group label: identical placebo
arm group type: Placebo Comparator
description: identical placebo po bid for one year
intervention type: Dietary Supplement
intervention name: Pyridoxamine Dihydrochloride
description: pyridoxamine dihydrochloride (over- the- counter type of vitamin B6) 200 mg po bid
arm group label: pyridoxamine
intervention type: Drug
intervention name: placebo
description: placebo
arm group label: identical placebo
criteria: 
gender: Female
minimum age: 65 Years
maximum age: N/A
healthy volunteers: No
last name: Mishaela Rubin,, M.D
role: Principal Investigator
affiliation: Columbia University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Columbia University
investigator full name: Mishaela Rubin
investigator title: Associate Professor of Medicine
mesh term: Diabetes Mellitus, Type 2
mesh term: Pyridoxamine
provided document: 