<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/NCT03282981</url>
  </required_header>
  <id_info>
    <org_study_id>SURG-004-16F</org_study_id>
    <secondary_id>17-08-00792</secondary_id>
    <nct_id>NCT03282981</nct_id>
  </id_info>
  <brief_title>Beta Adrenergic Antagonist for the Healing of Chronic DFU</brief_title>
  <acronym>BAART-DFU</acronym>
  <official_title>Beta Adrenergic Antagonist For The Healing of Chronic Diabetic Foot Ulcers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>VA Northern California Health Care System</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>VA Office of Research and Development</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      One in four Veterans is affected by diabetes and will develop a diabetic foot ulcer. Diabetic&#xD;
      ulcers are very challenging to manage and are the most common cause of leg amputation. Many&#xD;
      advanced treatments are expensive and difficult to use in the clinic or at home. Those newer&#xD;
      therapies have shown little success in healing diabetic foot wounds. The investigators'&#xD;
      laboratory and animal work has suggested that a safe medication, currently used as an eye&#xD;
      drop for treatment of glaucoma, can heal these ulcers. The investigators are proposing to&#xD;
      test this drop (timolol) directly on the surface of the foot ulcer to see if can improve&#xD;
      healing faster than the current standard of care. To do this, the investigators propose a&#xD;
      &quot;randomized controlled trial&quot; with two groups of patients with diabetic foot ulcers: one will&#xD;
      receive standard of care with timolol while the other will receive standard of care with a&#xD;
      gel (hydrogel, as placebo medicine).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The trial is designed as a prospective, randomized, double-blinded controlled study of&#xD;
      subjects presenting with diabetic foot ulcers. The purpose of this study is to evaluate the&#xD;
      superiority of Timoptic-XE therapy in conjunction with standard of care (SOC) treatment&#xD;
      (Group A: Timoptic-XE + SOC) versus SOC (Group B: SOC + plus a non-biologically active gel,&#xD;
      i.e., hydrogel, as placebo medication) in the clinical effectiveness in promoting wound&#xD;
      healing and closure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 14, 2018</start_date>
  <completion_date type="Anticipated">March 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2023</primary_completion_date>
  <phase>Phase 3</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to complete wound closure, as assessed over a 12 week period</measure>
    <time_frame>12 weeks</time_frame>
    <description>Complete wound closure will be assessed by Investigators and is defined as 100% epithelialization of the wound site (&quot;skin re-epithelialization without drainage or dressing requirements by Week 12).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Measurement of timolol serum during the treatment phase</measure>
    <time_frame>31 weeks</time_frame>
    <description>Primary safety outcome</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The time to wound closure between the two groups</measure>
    <time_frame>31 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Chronic Diabetic Foot Ulcers</condition>
  <condition>Diabetic Neuropathic Ulcers</condition>
  <condition>Non Healing Wound</condition>
  <arm_group>
    <arm_group_label>Timolol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Timoptic-XE plus standard of care (SOC)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SOC plus non biologically active gel</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>SOC plus non biologically active gel (hydrogel as placebo medication)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Timolol</intervention_name>
    <description>Topical application of Timolol on non-healing diabetic foot ulcers</description>
    <arm_group_label>Timolol</arm_group_label>
    <other_name>Timoptic-XE</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Non biologically active gel</intervention_name>
    <description>Topical application of non biologically active gel (Hydrogel- standard of care) on non-healing diabetic foot ulcers</description>
    <arm_group_label>SOC plus non biologically active gel</arm_group_label>
    <other_name>Hydrogel</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female subject of any race 18 years old or older&#xD;
&#xD;
          -  Lower extremity ulcer located anywhere on the foot (as defined as beginning below the&#xD;
             malleoli of the ankle):&#xD;
&#xD;
               -  Of more than 30 days duration and less than 2 years duration&#xD;
&#xD;
               -  Surface area between 0.5cm2 and 20cm2 (as measured with the Silhouette imaging&#xD;
                  system at randomization). The ulcer with largest surface area meeting inclusion&#xD;
                  criteria will be selected as index ulcer&#xD;
&#xD;
               -  If two ulcers present with the same surface area, the ulcer of the longest&#xD;
                  duration will be selected as index ulcer&#xD;
&#xD;
          -  Documented Ankle Brachial Index (ABI) between 0.8 and 1.2 on the study limb or toe&#xD;
             pressure over 65mmHg within 3 months of screening phase&#xD;
&#xD;
          -  Documented biopsy report to rule out malignancy of ulcer of &gt; 6 months duration&#xD;
&#xD;
          -  Subject or legally authorized representative understands and is willing to give&#xD;
             written informed consent&#xD;
&#xD;
          -  Subject or legally authorized representative is willing and able to comply with a&#xD;
             trial (13 to 17 days) of protocol-specified standard care prior to randomization and&#xD;
             to comply with all study requirements&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Ulcer of non-diabetic etiology, such as venous, arterial and burn wounds&#xD;
&#xD;
          -  Index ulcer is less than 3 cm in distance from any other ulcer on the same extremity&#xD;
&#xD;
          -  There are greater than 3 ulcers on the study foot&#xD;
&#xD;
          -  Index ulcer presents with any of the following: cellulitis, osteomyelitis, exposed&#xD;
             bone, tendon or fascia, capsule , purulent exudate or gangrene&#xD;
&#xD;
          -  Index ulcer shows evidence of infection (defined as a moderate or severe rating of all&#xD;
             of the following clinical signs/symptoms:&#xD;
&#xD;
               -  increased warmth&#xD;
&#xD;
               -  increased pain&#xD;
&#xD;
               -  erythema&#xD;
&#xD;
               -  malodorous exudate at Screening or at Randomization (Visit 1), OR total organism&#xD;
                  count &gt; 1 x 105 colony forming units (CFU) from the screening visit study ulcer&#xD;
                  culture sample)&#xD;
&#xD;
          -  Index ulcer surface area has decreased or increased &gt; 40% between Screening and at&#xD;
             Randomization (Visit 1) as assessed by the Silhouette imaging system&#xD;
&#xD;
          -  Has acquired or is known to be infected with Human Immunodeficiency Virus (HIV)&#xD;
&#xD;
          -  Has active malignancy on the study foot&#xD;
&#xD;
          -  Has uncontrolled diabetes mellitus as defined by glycosylated hemoglobin A1C &gt; 12%&#xD;
&#xD;
          -  Has immunodeficiency as defined by serum IgG, IgA, and IgM less than one-half the&#xD;
             lower limit of normal&#xD;
&#xD;
          -  Has severe protein malnutrition as defined by serum albumin &lt; 2.5 g/dL&#xD;
&#xD;
          -  Has serum aspartate aminotransferase (AST, SGOT, GOT) or serum alanine&#xD;
             aminotransferase (ALT, SGPT, GPT) levels greater than twice the upper limit of normal&#xD;
&#xD;
          -  Has fatigue, palpitations, dyspnea, and/or angina at rest&#xD;
&#xD;
          -  Has a history, within the previous 12 months from date of Screening Visit, of alcohol&#xD;
             or drug abuse, particularly methadone or heroin&#xD;
&#xD;
          -  Has received previous treatment with the following during the 60 days prior to&#xD;
             Screening:&#xD;
&#xD;
               -  Immunosuppressive agents&#xD;
&#xD;
               -  radiation&#xD;
&#xD;
               -  chemotherapy&#xD;
&#xD;
               -  growth factors (epidermal growth factor, tumor necrosis factor, transforming&#xD;
                  growth factor, platelet derived growth factor, etc.)&#xD;
&#xD;
                    -  at the site of the study ulcer, split- or full-thickness skin graft at the&#xD;
                       site of the study ulcer, biologically-active (or engineered) cellular or&#xD;
                       acellular product(s) at the site of the study ulcer, investigational drug or&#xD;
                       device&#xD;
&#xD;
          -  Has been hospitalized for treatment of a diabetic foot ulcer within the previous 30&#xD;
             days from Screening&#xD;
&#xD;
          -  Has history of heart block 2nd and 3rd degree&#xD;
&#xD;
          -  Female who is pregnant or refuses to use adequate contraceptive methods and is of&#xD;
             childbearing age during the trial&#xD;
&#xD;
          -  Prisoners, institutionalized individuals or vulnerable population&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sara E. Dahle, DPM MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>VA Northern California Health Care System, Mather, CA</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rivkah R. Isseroff, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>VA Northern California Health Care System, Mather, CA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>VA Northern California Health Care System, Mather, CA</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95655-4200</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <last_update_submitted>September 6, 2023</last_update_submitted>
  <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetic Foot</mesh_term>
    <mesh_term>Foot Ulcer</mesh_term>
    <mesh_term>Ulcer</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Timolol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03282981
org study id: SURG-004-16F
secondary id: 17-08-00792
nct id: NCT03282981
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
One in four Veterans is affected by diabetes and will develop a diabetic foot ulcer. Diabetic
      ulcers are very challenging to manage and are the most common cause of leg amputation. Many
      advanced treatments are expensive and difficult to use in the clinic or at home. Those newer
      therapies have shown little success in healing diabetic foot wounds. The investigators'
      laboratory and animal work has suggested that a safe medication, currently used as an eye
      drop for treatment of glaucoma, can heal these ulcers. The investigators are proposing to
      test this drop (timolol) directly on the surface of the foot ulcer to see if can improve
      healing faster than the current standard of care. To do this, the investigators propose a
      "randomized controlled trial" with two groups of patients with diabetic foot ulcers: one will
      receive standard of care with timolol while the other will receive standard of care with a
      gel (hydrogel, as placebo medicine).
The trial is designed as a prospective, randomized, double-blinded controlled study of
      subjects presenting with diabetic foot ulcers. The purpose of this study is to evaluate the
      superiority of Timoptic-XE therapy in conjunction with standard of care (SOC) treatment
      (Group A: Timoptic-XE + SOC) versus SOC (Group B: SOC + plus a non-biologically active gel,
      i.e., hydrogel, as placebo medication) in the clinical effectiveness in promoting wound
      healing and closure.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Time to complete wound closure, as assessed over a 12 week period
time frame: 12 weeks
description: Complete wound closure will be assessed by Investigators and is defined as 100% epithelialization of the wound site ("skin re-epithelialization without drainage or dressing requirements by Week 12).
measure: Measurement of timolol serum during the treatment phase
time frame: 31 weeks
description: Primary safety outcome
measure: The time to wound closure between the two groups
time frame: 31 weeks
arm group label: Timolol
arm group type: Experimental
description: Timoptic-XE plus standard of care (SOC)
arm group label: SOC plus non biologically active gel
arm group type: Placebo Comparator
description: SOC plus non biologically active gel (hydrogel as placebo medication)
intervention type: Drug
intervention name: Timolol
description: Topical application of Timolol on non-healing diabetic foot ulcers
arm group label: Timolol
other name: Timoptic-XE
intervention type: Drug
intervention name: Non biologically active gel
description: Topical application of non biologically active gel (Hydrogel- standard of care) on non-healing diabetic foot ulcers
arm group label: SOC plus non biologically active gel
other name: Hydrogel
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sara E. Dahle, DPM MPH
role: Principal Investigator
affiliation: VA Northern California Health Care System, Mather, CA
last name: Rivkah R. Isseroff, MD
role: Principal Investigator
affiliation: VA Northern California Health Care System, Mather, CA
facility: 
country: United States
responsible party type: Sponsor
mesh term: Diabetic Foot
mesh term: Foot Ulcer
mesh term: Ulcer
mesh term: Timolol
sharing ipd: No