<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/NCT02213094</url>
  </required_header>
  <id_info>
    <org_study_id>13-2203</org_study_id>
    <nct_id>NCT02213094</nct_id>
  </id_info>
  <brief_title>Phase I Study of Nicotinamide for Early Onset Preeclampsia</brief_title>
  <official_title>Phase I Study of Nicotinamide for Early Onset Preeclampsia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>North Carolina Translational and Clinical Sciences Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of North Carolina, Chapel Hill</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase I study of vitamin B3-amide (nicotinamide) dietary supplementation in&#xD;
      pregnant women with early onset preeclampsia. The investigators will enroll 10 pregnant women&#xD;
      at 24-32 weeks' gestation with the diagnosis of preeclampsia. If the woman is anticipated to&#xD;
      remain undelivered for 48 hours after diagnosis she will receive vitamin B3-amide, 500 mg/day&#xD;
      given in the morning (n=5) or 1000 mg given in the morning (n=5), continuing until delivery&#xD;
      or for 14 days, whichever occurs first. Maternal blood will be collected at baseline and&#xD;
      twice a day on days 1, 3, and 7 of nicotinamide administration to measure nicotinamide&#xD;
      metabolites, The objectives of this Phase I study are to to test safety of nicotinamide.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2014</start_date>
  <completion_date type="Actual">December 3, 2015</completion_date>
  <primary_completion_date type="Actual">December 3, 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Phase 1 dose escalation study</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Adverse Events</measure>
    <time_frame>Within 48 hours of dosing</time_frame>
    <description>Specific adverse events were Maternal liver toxicity, defined as &gt; 3x ULN of ALT(Alanine amniotransferase) or AST (Aspartate amniotransferase), maternal report of side effects, and fetal adverse effects.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Pregnancy Induced Hypertension</condition>
  <condition>Superimposed Preeclampsia</condition>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>Nicotinamide 500 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nicotinamide 500 mg by mouth each morning until delivery or 14 days, whichever occurs first.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Nicotinamide 1000 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nicotinamide 1000 mg by mouth each morning until delivery or 14 days, whichever occurs first.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nicotinamide 500 mg</intervention_name>
    <description>Nicotinamide 500 mg taken by mouth each morning</description>
    <arm_group_label>Nicotinamide 500 mg</arm_group_label>
    <other_name>Vitamin B3 amide</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nicotinamide 1000 mg</intervention_name>
    <description>Nicotinamide 1000 mg taken by mouth each morning</description>
    <arm_group_label>Nicotinamide 1000 mg</arm_group_label>
    <other_name>Vitamin B3 amide</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Maternal age 18-45 years&#xD;
&#xD;
          2. Informed written consent&#xD;
&#xD;
          3. Preeclampsia or new onset hypertension between 24-32 completed weeks' gestation&#xD;
&#xD;
               1. Hypertensive complications of pregnancy defined as new onset systolic BP &gt; 140 mm&#xD;
                  Hg and/or diastolic BP &gt; 90 mm Hg on two occasions 6 hours apart; OR &gt; 300 mg&#xD;
                  proteinuria on 24 hour urine collection OR urine P/C ratio &gt;0.3;&#xD;
&#xD;
               2. Dating criteria based on menstrual dating confirmed by first or second trimester&#xD;
                  ultrasound OR second trimester ultrasound if menstrual dating unavailable;&#xD;
&#xD;
               3. Deemed clinically stable by primary clinician and candidate for expectant&#xD;
                  management (delayed delivery);&#xD;
&#xD;
          4. Maternal liver function tests &lt; 3x ULN&#xD;
&#xD;
          5. Maternal platelet count &gt; 100,000 mm3&#xD;
&#xD;
          6. Fetal well-being established by estimated fetal weight &gt; 5th %tile; normal amniotic&#xD;
             fluid volume (MVP &gt; 2 cm); normal Umbilical Artery Dopplers; AND reactive&#xD;
             NST(non-stress test) or BPP (biophysical profile) &gt; 6&#xD;
&#xD;
          7. Plan for expectant management until delivery&#xD;
&#xD;
          8. Delivery not anticipated within first 48 hours&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Preeclampsia &lt; 24 or &gt; 33 weeks' gestation;&#xD;
&#xD;
          2. Suspected fetal structural or chromosomal abnormality;&#xD;
&#xD;
          3. Pre-existing renal disease (creatinine &gt; 1.5 mg/dL)&#xD;
&#xD;
          4. Pre-existing vascular disease (systemic lupus; cardiac disease;)&#xD;
&#xD;
          5. Plan for delivery within 48 hours&#xD;
&#xD;
          6. Any pre-existing medical condition that would increase risk for liver toxicity (e.g.&#xD;
             hepatitis B or C; HIV)&#xD;
&#xD;
          7. Evidence of cerebral dysfunction (seizures; cerebral edema on CT/MRI; headache&#xD;
             unresolved with oral analgesics)&#xD;
&#xD;
          8. Pulmonary edema&#xD;
&#xD;
          9. HELLP (hemolysis, elevated liver enzymes, low platelets syndrome)&#xD;
&#xD;
         10. Evidence of liver dysfunction (LFTs &gt; 3x ULN)&#xD;
&#xD;
         11. Thrombocytopenia (platelets &lt; 100,000 mm3)&#xD;
&#xD;
         12. Evidence of fetal compromise: EFW(estimated fetal weight) &lt; 5th percentile; BPP &lt; 6;&#xD;
             absent or reverse diastolic UA blood flow; oligohydramnios (MVP &lt; 2 cm)&#xD;
&#xD;
         13. Placental abruption defined as unexplained vaginal bleeding&#xD;
&#xD;
         14. Preterm labor defined as regular contractions and cervical change&#xD;
&#xD;
         15. Any condition deemed by the investigator to be a risk to mother or fetus in completion&#xD;
             of the study&#xD;
&#xD;
         16. Any condition deemed by the investigator to require delivery within 48 hours&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kim A Boggess, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina, Chapel Hill</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of North Carolina Women's Hospital</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599-7516</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>August 7, 2014</study_first_submitted>
  <study_first_submitted_qc>August 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 11, 2014</study_first_posted>
  <results_first_submitted>January 22, 2018</results_first_submitted>
  <results_first_submitted_qc>March 15, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">November 2, 2018</results_first_posted>
  <last_update_submitted>March 15, 2018</last_update_submitted>
  <last_update_submitted_qc>March 15, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 2, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>preeclampsia</keyword>
  <keyword>pregnancy-induced hypertension</keyword>
  <keyword>nicotinamide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pre-Eclampsia</mesh_term>
    <mesh_term>Hypertension, Pregnancy-Induced</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamins</mesh_term>
    <mesh_term>Niacinamide</mesh_term>
    <mesh_term>Niacin</mesh_term>
    <mesh_term>Nicotinic Acids</mesh_term>
    <mesh_term>Vitamin B Complex</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Nicotinamide 500 mg</title>
          <description>Nicotinamide 500 mg by mouth each morning until delivery or 14 days, whichever occurs first.</description>
        </group>
        <group group_id="P2">
          <title>Nicotinamide 1000 mg</title>
          <description>Nicotinamide 1000 mg by mouth each morning until delivery or 14 days, whichever occurs first.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4">One subject stopped study agent early because of elevation in LFTs &gt; 3x ULN</participants>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Nicotinamide 500 mg</title>
          <description>Nicotinamide 500 mg by mouth each morning until delivery or 14 days, whichever occurs first.</description>
        </group>
        <group group_id="B2">
          <title>Nicotinamide 1000 mg</title>
          <description>Nicotinamide 1000 mg by mouth each morning until delivery or 14 days, whichever occurs first.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
            <count group_id="B2" value="5"/>
            <count group_id="B3" value="10"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Adverse Events</title>
        <description>Specific adverse events were Maternal liver toxicity, defined as &gt; 3x ULN of ALT(Alanine amniotransferase) or AST (Aspartate amniotransferase), maternal report of side effects, and fetal adverse effects.</description>
        <time_frame>Within 48 hours of dosing</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Nicotinamide 500 mg</title>
            <description>Nicotinamide 500 mg by mouth each morning until delivery or 14 days, whichever occurs first.</description>
          </group>
          <group group_id="O2">
            <title>Nicotinamide 1000 mg</title>
            <description>Nicotinamide 1000 mg by mouth each morning until delivery or 14 days, whichever occurs first.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events</title>
          <description>Specific adverse events were Maternal liver toxicity, defined as &gt; 3x ULN of ALT(Alanine amniotransferase) or AST (Aspartate amniotransferase), maternal report of side effects, and fetal adverse effects.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>During study agent administration (up to 14 days)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Nicotinamide 500 mg</title>
          <description>Nicotinamide 500 mg by mouth each morning until delivery or 14 days, whichever occurs first.</description>
        </group>
        <group group_id="E2">
          <title>Nicotinamide 1000 mg</title>
          <description>Nicotinamide 1000 mg by mouth each morning until delivery or 14 days, whichever occurs first.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Elevated LFTs</sub_title>
                <description>Subject #4 had elevated LFTs &lt; 24 hours after first dose of study agent. This was believed to be due to the disease process and thus the primary clinical provider opted to proceed with infant delivery, therefore study agent was discontinued.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal failure</sub_title>
                <description>Subject #5 required dialysis following delivery of her infant. Her serum creatinine was normal at enrollment and throughout study agent administration. She developed renal failure following delivery, which required 2 dialysis treatments.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Kim Boggess MD Principal Investigator</name_or_title>
      <organization>UNC at Chapel Hill</organization>
      <phone>919-966-1601</phone>
      <email>kboggess@med.unc.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02213094
org study id: 13-2203
nct id: NCT02213094
lead sponsor: 
collaborator: 
has dmc: Yes
This is a Phase I study of vitamin B3-amide (nicotinamide) dietary supplementation in
      pregnant women with early onset preeclampsia. The investigators will enroll 10 pregnant women
      at 24-32 weeks' gestation with the diagnosis of preeclampsia. If the woman is anticipated to
      remain undelivered for 48 hours after diagnosis she will receive vitamin B3-amide, 500 mg/day
      given in the morning (n=5) or 1000 mg given in the morning (n=5), continuing until delivery
      or for 14 days, whichever occurs first. Maternal blood will be collected at baseline and
      twice a day on days 1, 3, and 7 of nicotinamide administration to measure nicotinamide
      metabolites, The objectives of this Phase I study are to to test safety of nicotinamide.
allocation: Randomized
intervention model: Single Group Assignment
intervention model description: Phase 1 dose escalation study
primary purpose: Other
masking: None (Open Label)
measure: Number of Participants With Adverse Events
time frame: Within 48 hours of dosing
description: Specific adverse events were Maternal liver toxicity, defined as > 3x ULN of ALT(Alanine amniotransferase) or AST (Aspartate amniotransferase), maternal report of side effects, and fetal adverse effects.
arm group label: Nicotinamide 500 mg
arm group type: Experimental
description: Nicotinamide 500 mg by mouth each morning until delivery or 14 days, whichever occurs first.
arm group label: Nicotinamide 1000 mg
arm group type: Experimental
description: Nicotinamide 1000 mg by mouth each morning until delivery or 14 days, whichever occurs first.
intervention type: Drug
intervention name: Nicotinamide 500 mg
description: Nicotinamide 500 mg taken by mouth each morning
arm group label: Nicotinamide 500 mg
other name: Vitamin B3 amide
intervention type: Drug
intervention name: Nicotinamide 1000 mg
description: Nicotinamide 1000 mg taken by mouth each morning
arm group label: Nicotinamide 1000 mg
other name: Vitamin B3 amide
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Kim A Boggess, MD
role: Principal Investigator
affiliation: University of North Carolina, Chapel Hill
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pre-Eclampsia
mesh term: Hypertension, Pregnancy-Induced
mesh term: Hypertension
mesh term: Vitamins
mesh term: Niacinamide
mesh term: Niacin
mesh term: Nicotinic Acids
mesh term: Vitamin B Complex
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 