<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/NCT02989961</url>
  </required_header>
  <id_info>
    <org_study_id>Resticutis.UJCTC</org_study_id>
    <nct_id>NCT02989961</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Resticutis Compared to Platelet-Poor Plasma for Treating Diabetic Foot Ulcers</brief_title>
  <official_title>Autologous Intra-lesional Injection of Resticutis Compared to Platelet-Poor Plasma to Improve Healing of Wagner's Grade II/III Diabetic Foot Ulcers (Neuropathic/Neuro-Iscemic)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hanan Jafar</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Jordan</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the safety of Resticutis for the treatment of&#xD;
      Wagner's Grade II/III diabetic foot ulcers in comparison with Platelet-Poor Plasma as a&#xD;
      placebo comparator.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Grade II and III (According to Wagner's classification system of Ulcer severity) are&#xD;
      considered to be of the most common complications associated with Diabetes, which are mostly&#xD;
      hard to heal using the conventional treatment methods which by consequence severely affects&#xD;
      the quality and lifestyle of the diabetes patient.&#xD;
&#xD;
      It's thought that the application of Autologous activated platelets &quot;Resticutis&quot; which&#xD;
      secretes huge amounts of growth factors is capable of giving better results of which are: the&#xD;
      stimulation of the healing process that includes contraction, granulation, tissue formation&#xD;
      and epithelialization of the diabetic foot ulcer.&#xD;
&#xD;
      Resticutis is obtained from an autologous 20 mL peripheral blood withdrawn in tubes&#xD;
      containing 3.8% Sodium Citrate. Blood is then centrifuged to obtain Platelet-Rich Plasma&#xD;
      -PRP- as per established method. PRP is then activated in a closed system by physical methods&#xD;
      to obtain a final product of 5 mL of Resticutis which is injected intra-lesionally at ulcer&#xD;
      margins per each session of therapy.&#xD;
&#xD;
      It's hypothesized that a total of six injections throughout the period of the treatment are&#xD;
      enough to achieve full closure of the DFU. The injections are given on days: 0,14,28,42,56,&#xD;
      and 70 of the treatment period.&#xD;
&#xD;
      The consenting patients will be randomized into 2 groups: One group will be given Resticutis,&#xD;
      and the second one Platelet-Poor Plasma PPP as placebo. If patients in PPP group didn't&#xD;
      achieve full healing after four-six injections, they're given a two weeks rest after which&#xD;
      they are given Resticutis instead.&#xD;
&#xD;
      This is mainly a phase 1 safety study, which means no formal statistical analysis will be&#xD;
      applied to any of the data. Safety assessment will depend on the association of any adverse&#xD;
      events during the course of the study, and efficacy as a secondary objective will be assessed&#xD;
      by observing the healing time of DFUs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">November 15, 2013</start_date>
  <completion_date type="Anticipated">November 2019</completion_date>
  <primary_completion_date type="Actual">March 13, 2018</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]) as a result of the injection</measure>
    <time_frame>2 months</time_frame>
    <description>Evaluate the safety of this treatment, by gathering and assessing the number, timing, severity, duration, and resolution of related adverse events.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assess the efficacy of autologous Resticutis injection by clinical examination</measure>
    <time_frame>4 months</time_frame>
    <description>To determine short term speed and effectiveness of autologous Resticutis as a platelet lysate derivative on the healing of diabetic foot ulceration compared with Platelet Poor Plasma by measuring the healing time.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Diabetic Foot Ulcer</condition>
  <arm_group>
    <arm_group_label>A-Resticutis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Autologous, Activated-Platelets type of preparation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C-Platelet-Poor Plasma PPP</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Platelet-Poor Plasma type of preparation achieved by centrifugation of blood samples at high speed conditions. Resticutis is administered instead if the patient doesn't achieve full healing after 6 injections.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Resticutis</intervention_name>
    <description>Autologous, Activated-Platelets type of Preparation</description>
    <arm_group_label>A-Resticutis</arm_group_label>
    <arm_group_label>C-Platelet-Poor Plasma PPP</arm_group_label>
    <other_name>Actiplate 1</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Platelet-Poor Plasma (PPP)</intervention_name>
    <description>A preparation of low platelet plasma obtained by a high-speed centrifugation step.</description>
    <arm_group_label>C-Platelet-Poor Plasma PPP</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  People with Type II Diabetes mellitus between the ages of 18 and 70 with an ulcer with&#xD;
             at least 4 weeks duration.&#xD;
&#xD;
          -  Hb1c of less than 13 %.&#xD;
&#xD;
          -  Index foot ulcer located on the plantar, medial, or lateral aspect of the foot&#xD;
             (including all toe surfaces), and wound area (length*width) measurement between 0.5&#xD;
             cm^2 and 20 cm^2, inclusive.&#xD;
&#xD;
          -  Wounds located under a Charcot deformity has to be free of acute changes and went&#xD;
             through appropriate structural consolidation.&#xD;
&#xD;
          -  Wagner Grade II or III ulcer.&#xD;
&#xD;
          -  The protocol requires that post-debridement, the ulcer would be free of necrotic&#xD;
             debris, foreign bodies, or sinus tracts.&#xD;
&#xD;
          -  Non invasive vascular testing Ankle Brachial Index (ABI).&#xD;
&#xD;
          -  Physical examination (Including a Semmes-Weinstein monofilament test for neuropathy).&#xD;
&#xD;
          -  Blood tests to be obtained (CBC, Hb1c)&#xD;
&#xD;
          -  Approved, informed, signed consent to be obtained from each patient.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient currently enrolled in another investigative device or drug trial or previously&#xD;
             enrolled (within the last 30 days) in an investigative research of a device or a&#xD;
             pharmaceutical agent.&#xD;
&#xD;
          -  Ulcer area decreased &gt; 50% during the seven-day screening period.&#xD;
&#xD;
          -  Ulcer is due to a non-diabetic etiology.&#xD;
&#xD;
          -  Evidence of gangrene in ulcer or on any part of the foot.&#xD;
&#xD;
          -  Patient is currently receiving or has received radiation or chemotherapy within the&#xD;
             last 3 months of randomization.&#xD;
&#xD;
          -  Patient has received growth factor therapy within 7 days of randomization.&#xD;
&#xD;
          -  Screening platelets count &lt; 100* 10^9/L.&#xD;
&#xD;
          -  Patient is undergoing renal dialysis, or has a known immune insufficiency, known&#xD;
             abnormal platelets activation disorder (i.e. Grey Platelet Syndrome, Liver Disease,&#xD;
             Active Cancer), eating/nutritional, hematologic, collagen vascular disease, rheumatic&#xD;
             disease, or bleeding disorder.&#xD;
&#xD;
          -  History of peripheral vascular repair within 30 days of randomization.&#xD;
&#xD;
          -  Patient is known to have a physiological, developmental, physical, emotional, or&#xD;
             social disorder, or any other situation that may interfere with their compliance with&#xD;
             the study requirements and/or the healing of the ulcer.&#xD;
&#xD;
          -  History of alcohol or drug abuse within the last year prior to randomization.&#xD;
&#xD;
          -  Patient has inadequate venous access for blood withdraw.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>November 29, 2016</study_first_submitted>
  <study_first_submitted_qc>December 9, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 12, 2016</study_first_posted>
  <last_update_submitted>April 9, 2019</last_update_submitted>
  <last_update_submitted_qc>April 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 10, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Jordan</investigator_affiliation>
    <investigator_full_name>Hanan Jafar</investigator_full_name>
    <investigator_title>Researcher</investigator_title>
  </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>
  <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/NCT02989961
org study id: Resticutis.UJCTC
nct id: NCT02989961
lead sponsor: 
has dmc: Yes
The purpose of this study is to determine the safety of Resticutis for the treatment of
      Wagner's Grade II/III diabetic foot ulcers in comparison with Platelet-Poor Plasma as a
      placebo comparator.
Grade II and III (According to Wagner's classification system of Ulcer severity) are
      considered to be of the most common complications associated with Diabetes, which are mostly
      hard to heal using the conventional treatment methods which by consequence severely affects
      the quality and lifestyle of the diabetes patient.

      It's thought that the application of Autologous activated platelets "Resticutis" which
      secretes huge amounts of growth factors is capable of giving better results of which are: the
      stimulation of the healing process that includes contraction, granulation, tissue formation
      and epithelialization of the diabetic foot ulcer.

      Resticutis is obtained from an autologous 20 mL peripheral blood withdrawn in tubes
      containing 3.8% Sodium Citrate. Blood is then centrifuged to obtain Platelet-Rich Plasma
      -PRP- as per established method. PRP is then activated in a closed system by physical methods
      to obtain a final product of 5 mL of Resticutis which is injected intra-lesionally at ulcer
      margins per each session of therapy.

      It's hypothesized that a total of six injections throughout the period of the treatment are
      enough to achieve full closure of the DFU. The injections are given on days: 0,14,28,42,56,
      and 70 of the treatment period.

      The consenting patients will be randomized into 2 groups: One group will be given Resticutis,
      and the second one Platelet-Poor Plasma PPP as placebo. If patients in PPP group didn't
      achieve full healing after four-six injections, they're given a two weeks rest after which
      they are given Resticutis instead.

      This is mainly a phase 1 safety study, which means no formal statistical analysis will be
      applied to any of the data. Safety assessment will depend on the association of any adverse
      events during the course of the study, and efficacy as a secondary objective will be assessed
      by observing the healing time of DFUs.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]) as a result of the injection
time frame: 2 months
description: Evaluate the safety of this treatment, by gathering and assessing the number, timing, severity, duration, and resolution of related adverse events.
measure: Assess the efficacy of autologous Resticutis injection by clinical examination
time frame: 4 months
description: To determine short term speed and effectiveness of autologous Resticutis as a platelet lysate derivative on the healing of diabetic foot ulceration compared with Platelet Poor Plasma by measuring the healing time.
arm group label: A-Resticutis
arm group type: Experimental
description: Autologous, Activated-Platelets type of preparation.
arm group label: C-Platelet-Poor Plasma PPP
arm group type: Placebo Comparator
description: Platelet-Poor Plasma type of preparation achieved by centrifugation of blood samples at high speed conditions. Resticutis is administered instead if the patient doesn't achieve full healing after 6 injections.
intervention type: Other
intervention name: Resticutis
description: Autologous, Activated-Platelets type of Preparation
arm group label: A-Resticutis
arm group label: C-Platelet-Poor Plasma PPP
other name: Actiplate 1
intervention type: Other
intervention name: Platelet-Poor Plasma (PPP)
description: A preparation of low platelet plasma obtained by a high-speed centrifugation step.
arm group label: C-Platelet-Poor Plasma PPP
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
responsible party type: Sponsor-Investigator
investigator affiliation: University of Jordan
investigator full name: Hanan Jafar
investigator title: Researcher
mesh term: Diabetic Foot
mesh term: Foot Ulcer
mesh term: Ulcer
sharing ipd: No