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/NCT06042699</url>
    </required_header>
    <id_info>
      <org_study_id>AAAU2577</org_study_id>
      <secondary_id>K23GM152933-01</secondary_id>
      <nct_id>NCT06042699</nct_id>
    </id_info>
    <brief_title>Scoliosis Iron Supplementation Study</brief_title>
    <official_title>Study of Iron Supplementation in Adolescents Undergoing Scoliosis Surgery</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Columbia University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Institute of General Medical Sciences (NIGMS)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>Columbia University</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>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study is a randomized controlled trial of preoperative oral iron supplementation, to&#xD;
        identify whether iron deficiency is a modifiable risk factor for adverse surgical outcomes&#xD;
        such as red blood cell transfusion and diminished postoperative cognitive and physical&#xD;
        capacity in adolescents undergoing scoliosis surgery.&#xD;
  &#xD;
        Research Question(s)/Hypothesis(es):&#xD;
  &#xD;
        Primary&#xD;
  &#xD;
          -  Iron supplementation will reduce the incidence of perioperative RBC transfusion in iron&#xD;
             deficient scoliosis patients undergoing spinal fusion.&#xD;
  &#xD;
        Secondary&#xD;
  &#xD;
          -  Iron supplementation will reduce postoperative neurocognitive functional declines in&#xD;
             iron deficient scoliosis patients undergoing spinal fusion.&#xD;
  &#xD;
          -  Iron supplementation will improve patient-reported physical functioning in iron&#xD;
             deficient scoliosis patients undergoing spinal fusion.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Adolescents undergoing spinal fusion surgery for scoliosis are poised to benefit from&#xD;
        preoperative iron supplementation. Spinal fusion carries a risk of large surgical blood&#xD;
        losses and perioperative red blood cell transfusion, which are associated with adverse&#xD;
        outcomes in this population. These patients are mostly adolescent females, a group more&#xD;
        susceptible to iron deficiency and resulting anemia at baseline due to iron losses with&#xD;
        menses, and who suffer an additional insult to iron stores during surgery. Nevertheless, iron&#xD;
        status is not routinely monitored in this setting and there is no standard of care for&#xD;
        preoperative iron supplementation. Iron is a nutritionally essential trace element important&#xD;
        not only for red blood cell production, but also for muscle function and neurotransmitter&#xD;
        synthesis and signaling. Therefore, the treatment of preoperative iron deficiency is an&#xD;
        important target for optimizing hemoglobin prior to surgery, reducing transfusion rates and&#xD;
        associated complications such as alloimmunization, and improving patient outcomes. On its own&#xD;
        and as the primary cause of anemia, iron deficiency was identified by the investigator's team&#xD;
        as the only risk factor for transfusion which is modifiable preoperatively.&#xD;
  &#xD;
        In addition, iron supplementation is shown to alleviate impairments of physical and cognitive&#xD;
        capacity associated with even mild forms of iron deficiency in adolescent females. A pilot&#xD;
        study conducted at the investigator's institution identified iron deficiency in 36% of&#xD;
        scoliosis patients prior to surgery, with preoperative iron status highly correlated with&#xD;
        iron status during surgical recovery. Consequently, the investigator plans to examine iron&#xD;
        deficiency as a modifiable risk factor for transfusion and impaired postoperative cognitive&#xD;
        and physical capacity in this vulnerable population. Previous trials of brief iron&#xD;
        interventions in high-risk adult surgical patients, mostly with unknown iron status, do not&#xD;
        inform the care of iron deficient adolescents and were not designed to address postoperative&#xD;
        functional outcomes. This study will therefore perform a single-center randomized controlled&#xD;
        trial in which adolescents with scoliosis will be screened for iron deficiency (n = ~275),&#xD;
        and iron-deficient adolescents with scoliosis (n = ~90) will be randomized to a preoperative&#xD;
        regimen of daily oral iron or placebo, to test the hypotheses that preoperative iron&#xD;
        supplementation 1) reduces the rate of red blood cell transfusion, 2) improves postoperative&#xD;
        neurocognition compared to a preoperative baseline, and 3) improves patient-reported physical&#xD;
        functioning during recovery. Results will ultimately improve outcomes in this vulnerable&#xD;
        pediatric population and provide evidence for patient blood management approaches to reduce&#xD;
        transfusions amid recent severe blood shortages.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">December 1, 2023</start_date>
    <completion_date type="Anticipated">January 30, 2028</completion_date>
    <primary_completion_date type="Anticipated">November 30, 2027</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>Double blind placebo-controlled randomized controlled trial</intervention_model_description>
      <primary_purpose>Prevention</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <masking_description>Placebo tablets will be indistinguishable from iron tablets. Group allocation will not be accessible to participants, care providers, investigators, or outcomes assessors.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence of perioperative RBC transfusion in iron deficient scoliosis patients undergoing spinal fusion</measure>
      <time_frame>4 to 30 days</time_frame>
      <description>The patients that received a red blood cell transfusion either during procedure or postoperatively during t surgical hospitalization will be tallied.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Percentage of Patients that experienced postoperative decline in neurocognitive function</measure>
      <time_frame>4-6 months</time_frame>
      <description>The Cognitive Battery of the NIH Toolbox is a brief, valid, and reliable instrument designed to provide outcome measures in epidemiologic and longitudinal research that can be used for comparisons across a wide range of studies and populations. Individual measure scores in the battery reflect Executive Function, Attention, Verbal and Nonverbal Memory, Language, Processing Speed, and Working Memory, yielding composite score. A decline of function is measured by comparing the mean change from baseline in the Cognitive Function Composite Scores in the study groups.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of patients that experienced postoperative decline in self-reported physical capacity</measure>
      <time_frame>4-6 months</time_frame>
      <description>The PROMIS pediatric measures are a NIH Roadmap initiative to provide access to valid and reliable self-reported measures of health-related quality of life in children and adolescents. The PROMIS measures are scored on a T-score metric with a mean of 50 and SD of 10 in the general population in the United States. Higher PROMIS symptom scores indicate increased symptom burden, and higher PROMIS function scores indicate increased functioning. Decline would be identified through a mean change (decrease) from baseline in the Physical Functioning - Mobility scores; with secondary hypotheses for Physical Functioning - Upper Extremity, Physical Activity, and Fatigue.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Volume of perioperative RBC transfusion</measure>
      <time_frame>4 to 30 days</time_frame>
      <description>The volume that each patient receives either during procedure or postoperatively during surgical hospitalization will be summed and average calculated.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">275</enrollment>
    <condition>Adolescent Idiopathic Scoliosis</condition>
    <condition>Neuromuscular Scoliosis</condition>
    <condition>Perioperative/Postoperative Complications</condition>
    <condition>Iron Deficiencies</condition>
    <condition>Anemia</condition>
    <condition>Spinal Fusion</condition>
    <condition>Postoperative Cognitive Dysfunction</condition>
    <arm_group>
      <arm_group_label>Oral ferrous sulfate</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive oral ferrous sulfate tablets, 325mg (65mg elemental iron). Tablets are to be taken once daily for 3-6 months prior to surgery as time allows.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Oral placebo tablets</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Participants will receive placebo tablets. Tablets are to be taken once daily for 3-6 months prior to surgery as time allows.</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Oral ferrous sulfate</intervention_name>
      <description>Oral ferrous sulfate 325mg is used as a dietary supplement providing 65mg elemental iron.</description>
      <arm_group_label>Oral ferrous sulfate</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Oral placebo tablet</intervention_name>
      <description>Oral placebo tablet provided as placebo comparator.</description>
      <arm_group_label>Oral placebo tablets</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  12-19 years old&#xD;
  &#xD;
            -  diagnosis of scoliosis&#xD;
  &#xD;
            -  ability to swallow a tablet&#xD;
  &#xD;
            -  spinal fusion procedure planned at least 13 weeks from when patient agrees to&#xD;
               phlebotomy for screening blood work&#xD;
  &#xD;
            -  serum ferritin less than or equal to 25 µg/L&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  taking or planning to take iron-containing supplement under the direction of a health&#xD;
               care provider, or under patient's own volition and and not willing to stop for&#xD;
               duration of study&#xD;
  &#xD;
            -  C-reactive protein &gt; 10 mg/L&#xD;
  &#xD;
            -  receiving nutritional support&#xD;
  &#xD;
            -  self-reported history of hypersensitivity reaction to iron-containing supplements&#xD;
  &#xD;
            -  self-reported history of or suspected non-iron deficient hematologic disorder&#xD;
  &#xD;
            -  self-reported history of iron overloaded state such as hereditary hemochromatosis or&#xD;
               hemosiderosis&#xD;
  &#xD;
            -  objection to receiving red blood cell transfusions&#xD;
  &#xD;
            -  current pregnancy (by self-report)&#xD;
  &#xD;
            -  prisoners&#xD;
  &#xD;
            -  patient or parent decides against study participation&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>12 Years</minimum_age>
      <maximum_age>19 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Lisa D Eisler, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Columbia University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Lisa Eisler, MD</last_name>
      <phone>212-305-2413</phone>
      <email>ldl2113@cumc.columbia.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>Columbia University Medical Center</name>
        <address>
          <city>New York</city>
          <state>New York</state>
          <zip>10032</zip>
          <country>United States</country>
        </address>
      </facility>
      <investigator>
        <last_name>Lisa Eisler, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 12, 2023</study_first_submitted>
    <study_first_submitted_qc>September 12, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 18, 2023</study_first_posted>
    <last_update_submitted>September 12, 2023</last_update_submitted>
    <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Columbia University</investigator_affiliation>
      <investigator_full_name>Lisa Eisler</investigator_full_name>
      <investigator_title>Assistant Professor of Anesthesiology</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Scoliosis</mesh_term>
      <mesh_term>Iron Deficiencies</mesh_term>
      <mesh_term>Postoperative Complications</mesh_term>
      <mesh_term>Postoperative Cognitive Complications</mesh_term>
      <mesh_term>Cognitive Dysfunction</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>IPD will not be shared.</ipd_description>
    </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/NCT06042699
  org study id: AAAU2577
  secondary id: K23GM152933-01
  nct id: NCT06042699
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  is us export: Yes
  This study is a randomized controlled trial of preoperative oral iron supplementation, to
        identify whether iron deficiency is a modifiable risk factor for adverse surgical outcomes
        such as red blood cell transfusion and diminished postoperative cognitive and physical
        capacity in adolescents undergoing scoliosis surgery.
  
        Research Question(s)/Hypothesis(es):
  
        Primary
  
          -  Iron supplementation will reduce the incidence of perioperative RBC transfusion in iron
             deficient scoliosis patients undergoing spinal fusion.
  
        Secondary
  
          -  Iron supplementation will reduce postoperative neurocognitive functional declines in
             iron deficient scoliosis patients undergoing spinal fusion.
  
          -  Iron supplementation will improve patient-reported physical functioning in iron
             deficient scoliosis patients undergoing spinal fusion.
  Adolescents undergoing spinal fusion surgery for scoliosis are poised to benefit from
        preoperative iron supplementation. Spinal fusion carries a risk of large surgical blood
        losses and perioperative red blood cell transfusion, which are associated with adverse
        outcomes in this population. These patients are mostly adolescent females, a group more
        susceptible to iron deficiency and resulting anemia at baseline due to iron losses with
        menses, and who suffer an additional insult to iron stores during surgery. Nevertheless, iron
        status is not routinely monitored in this setting and there is no standard of care for
        preoperative iron supplementation. Iron is a nutritionally essential trace element important
        not only for red blood cell production, but also for muscle function and neurotransmitter
        synthesis and signaling. Therefore, the treatment of preoperative iron deficiency is an
        important target for optimizing hemoglobin prior to surgery, reducing transfusion rates and
        associated complications such as alloimmunization, and improving patient outcomes. On its own
        and as the primary cause of anemia, iron deficiency was identified by the investigator's team
        as the only risk factor for transfusion which is modifiable preoperatively.
  
        In addition, iron supplementation is shown to alleviate impairments of physical and cognitive
        capacity associated with even mild forms of iron deficiency in adolescent females. A pilot
        study conducted at the investigator's institution identified iron deficiency in 36% of
        scoliosis patients prior to surgery, with preoperative iron status highly correlated with
        iron status during surgical recovery. Consequently, the investigator plans to examine iron
        deficiency as a modifiable risk factor for transfusion and impaired postoperative cognitive
        and physical capacity in this vulnerable population. Previous trials of brief iron
        interventions in high-risk adult surgical patients, mostly with unknown iron status, do not
        inform the care of iron deficient adolescents and were not designed to address postoperative
        functional outcomes. This study will therefore perform a single-center randomized controlled
        trial in which adolescents with scoliosis will be screened for iron deficiency (n = ~275),
        and iron-deficient adolescents with scoliosis (n = ~90) will be randomized to a preoperative
        regimen of daily oral iron or placebo, to test the hypotheses that preoperative iron
        supplementation 1) reduces the rate of red blood cell transfusion, 2) improves postoperative
        neurocognition compared to a preoperative baseline, and 3) improves patient-reported physical
        functioning during recovery. Results will ultimately improve outcomes in this vulnerable
        pediatric population and provide evidence for patient blood management approaches to reduce
        transfusions amid recent severe blood shortages.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Double blind placebo-controlled randomized controlled trial
  primary purpose: Prevention
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  masking description: Placebo tablets will be indistinguishable from iron tablets. Group allocation will not be accessible to participants, care providers, investigators, or outcomes assessors.
  measure: Incidence of perioperative RBC transfusion in iron deficient scoliosis patients undergoing spinal fusion
  time frame: 4 to 30 days
  description: The patients that received a red blood cell transfusion either during procedure or postoperatively during t surgical hospitalization will be tallied.
  measure: Percentage of Patients that experienced postoperative decline in neurocognitive function
  time frame: 4-6 months
  description: The Cognitive Battery of the NIH Toolbox is a brief, valid, and reliable instrument designed to provide outcome measures in epidemiologic and longitudinal research that can be used for comparisons across a wide range of studies and populations. Individual measure scores in the battery reflect Executive Function, Attention, Verbal and Nonverbal Memory, Language, Processing Speed, and Working Memory, yielding composite score. A decline of function is measured by comparing the mean change from baseline in the Cognitive Function Composite Scores in the study groups.
  measure: Percentage of patients that experienced postoperative decline in self-reported physical capacity
  time frame: 4-6 months
  description: The PROMIS pediatric measures are a NIH Roadmap initiative to provide access to valid and reliable self-reported measures of health-related quality of life in children and adolescents. The PROMIS measures are scored on a T-score metric with a mean of 50 and SD of 10 in the general population in the United States. Higher PROMIS symptom scores indicate increased symptom burden, and higher PROMIS function scores indicate increased functioning. Decline would be identified through a mean change (decrease) from baseline in the Physical Functioning - Mobility scores; with secondary hypotheses for Physical Functioning - Upper Extremity, Physical Activity, and Fatigue.
  measure: Volume of perioperative RBC transfusion
  time frame: 4 to 30 days
  description: The volume that each patient receives either during procedure or postoperatively during surgical hospitalization will be summed and average calculated.
  arm group label: Oral ferrous sulfate
  arm group type: Experimental
  description: Participants will receive oral ferrous sulfate tablets, 325mg (65mg elemental iron). Tablets are to be taken once daily for 3-6 months prior to surgery as time allows.
  arm group label: Oral placebo tablets
  arm group type: Placebo Comparator
  description: Participants will receive placebo tablets. Tablets are to be taken once daily for 3-6 months prior to surgery as time allows.
  intervention type: Dietary Supplement
  intervention name: Oral ferrous sulfate
  description: Oral ferrous sulfate 325mg is used as a dietary supplement providing 65mg elemental iron.
  arm group label: Oral ferrous sulfate
  intervention type: Dietary Supplement
  intervention name: Oral placebo tablet
  description: Oral placebo tablet provided as placebo comparator.
  arm group label: Oral placebo tablets
  criteria: 
  gender: All
  minimum age: 12 Years
  maximum age: 19 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Lisa D Eisler, MD
  role: Principal Investigator
  affiliation: Columbia University
  last name: Lisa Eisler, MD
  phone: 212-305-2413
  email: ldl2113@cumc.columbia.edu
  facility: 
  investigator: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: Columbia University
  investigator full name: Lisa Eisler
  investigator title: Assistant Professor of Anesthesiology
  mesh term: Scoliosis
  mesh term: Iron Deficiencies
  mesh term: Postoperative Complications
  mesh term: Postoperative Cognitive Complications
  mesh term: Cognitive Dysfunction
  sharing ipd: No
  ipd description: IPD will not be shared.