<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/NCT01675960</url>
  </required_header>
  <id_info>
    <org_study_id>112909</org_study_id>
    <nct_id>NCT01675960</nct_id>
  </id_info>
  <brief_title>Effectiveness of Gabapentin on Chronic Irritability in Neurologically Impaired Children</brief_title>
  <official_title>A Phase II, Randomized, Placebo-controlled, Double Blind, Cross-over, Study of the Effects of Gabapentin on Chronic Irritability in Neurologically Impaired Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gillette Children's Specialty Healthcare</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gillette Children's Specialty Healthcare</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is a prospective, randomized, double blind, placebo controlled, crossover clinical&#xD;
      trial looking at whether gabapentin can provide symptom relief for chronic irritability in&#xD;
      neurologically impaired children. The investigators hypothesize gabapentin ins beneficial and&#xD;
      safe for children with chronic irritability that persists despite identification and&#xD;
      appropriate management of symptom sources.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, placebo-controlled, cross-over study design of the effects of&#xD;
      gabapentin on chronic irritability in neurologically impaired children. The study will&#xD;
      involve a 22 day medication titration, followed by a 7 day stable dosing period and a 6 day&#xD;
      medication taper period. After an additional 3 day washout period, the subject will&#xD;
      cross-over to the remaining arm of the study. Subjects will be evaluated for symptoms of&#xD;
      chronic pain. Since the subjects are generally non-communicative, the subjects will be&#xD;
      evaluated by two questionnaires and the Non-Communicating Children's Pain Checklist-Revised,&#xD;
      to be completed by their parent or primary caregiver.&#xD;
&#xD;
      The primary aim is to determine if gabapentin provides symptom relief for chronic&#xD;
      irritability in neurologically impaired children.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    unable to enroll&#xD;
  </why_stopped>
  <start_date type="Actual">April 2012</start_date>
  <completion_date type="Actual">July 2017</completion_date>
  <primary_completion_date type="Actual">July 2017</primary_completion_date>
  <phase>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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Symptom Relief for Chronic Irritability in Neurologically Impaired Children Using Gabapentin.</measure>
    <time_frame>Compiled data reviewed at completion or withdrawal from study (3 months from beginning study).</time_frame>
    <description>We will determine whether gabapentin provides symptom relief for chronic irritability in neurologically impaired children, who continue to have irritability even though potential sources may have been identified and treated, or have sources that have not been identified.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Prevalence of Associated Gastrointestinal and Sleep Problems in Neurologically Impaired Children and Improvement Using Gabapentin.</measure>
    <time_frame>Compiled data reviewed at completion or withdrawal from study (3 months from beginning study).</time_frame>
    <description>We will attempt to identify gastrointestinal and sleep problems in neurologically impaired children with questionnaires given throughout the study. We hypothesize that gastrointestinal symptoms (feeding intolerance and symptoms associated with gas and bowel movements) and disrupted sleep are frequently associated with chronic irritability and will improve with gabapentin.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Neurologically Impaired</condition>
  <condition>Irritable Mood</condition>
  <condition>Signs and Symptoms, Digestive</condition>
  <condition>Sleeplessness</condition>
  <condition>Chronic Pain</condition>
  <arm_group>
    <arm_group_label>Gabapentin, then placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants first receive gabapentin 3 times per day, with varying dosing based on the protocol. After 34-38 days, a washout period of 3 days occurs, before then receiving the placebo dose for 32 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo, then Gabapentin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants first receive placebo 3 times per day. After 34-38 days, a washout period of 3 days occurs, before then receiving Gabapentin, with varying dosing based on the protocol, for 32 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gabapentin</intervention_name>
    <description>The active drug is in a flavored glycerin based solution. The drug will be given orally or through a gastrointestinal tube. Titration up to a stable dose will take 22 days. The total stable dose is 40mg/kg/day. Once 7 days on this dose are finished, children will take 6 days to reduce their dose and begin their 3 day washout period.</description>
    <arm_group_label>Gabapentin, then placebo</arm_group_label>
    <arm_group_label>Placebo, then Gabapentin</arm_group_label>
    <other_name>Fanatrex</other_name>
    <other_name>Neurontin</other_name>
    <other_name>Gabarone</other_name>
    <other_name>Gralise</other_name>
    <other_name>Horizant</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>The placebo is a glycerin-based clear solution that is flavored similarly to the commercial product. The placebo will be given orally or through a gastrointestinal tube.</description>
    <arm_group_label>Gabapentin, then placebo</arm_group_label>
    <arm_group_label>Placebo, then Gabapentin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  male or female&#xD;
&#xD;
          -  1 month to 16 years of age at enrollment&#xD;
&#xD;
          -  neurological impairment defined as subnormal (-2 S.D.) motor and/or cognitive ability&#xD;
             from a variety of etiologies&#xD;
&#xD;
          -  chronic irritability defined as symptoms suggesting pain to the child's caregiver&#xD;
             recurrently over a 4-week of greater time period&#xD;
&#xD;
          -  Subject must have an acceptable surrogate capable of giving consent on the subject's&#xD;
             behalf&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Children with resolved symptoms after treatment of identified sources of pain&#xD;
&#xD;
          -  Identified potential source of irritability without adequate trial of appropriate&#xD;
             management&#xD;
&#xD;
          -  Ketogenic diet&#xD;
&#xD;
          -  Renal insufficiency or failure&#xD;
&#xD;
          -  Current treatment with gabapentin or pregabalin for another existing condition.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Month</minimum_age>
    <maximum_age>16 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Scott Schwantes, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Gillette Children's Specialty Healthcare</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Gillette Children's Specialty Healthcare</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Perquin CW, Hazebroek-Kampschreur AAJM, Hunfeld JAM, Bohnen AM, van Suijlekom-Smit LWA, Passchier J, van der Wouden JC. Pain in children and adolescents: a common experience. Pain. 2000 Jul;87(1):51-58. doi: 10.1016/S0304-3959(00)00269-4.</citation>
    <PMID>10863045</PMID>
  </reference>
  <reference>
    <citation>Breau LM, Camfield CS, McGrath PJ, Finley GA. The incidence of pain in children with severe cognitive impairments. Arch Pediatr Adolesc Med. 2003 Dec;157(12):1219-26. doi: 10.1001/archpedi.157.12.1219.</citation>
    <PMID>14662579</PMID>
  </reference>
  <reference>
    <citation>Houlihan CM, O'Donnell M, Conaway M, Stevenson RD. Bodily pain and health-related quality of life in children with cerebral palsy. Dev Med Child Neurol. 2004 May;46(5):305-10. doi: 10.1017/s0012162204000507.</citation>
    <PMID>15132260</PMID>
  </reference>
  <reference>
    <citation>Stallard P, Williams L, Lenton S, Velleman R. Pain in cognitively impaired, non-communicating children. Arch Dis Child. 2001 Dec;85(6):460-2. doi: 10.1136/adc.85.6.460.</citation>
    <PMID>11719327</PMID>
  </reference>
  <reference>
    <citation>Greco C, Berde C. Pain management for the hospitalized pediatric patient. Pediatr Clin North Am. 2005 Aug;52(4):995-1027, vii-viii. doi: 10.1016/j.pcl.2005.04.005.</citation>
    <PMID>16009254</PMID>
  </reference>
  <reference>
    <citation>Breau LM, Camfield CS, McGrath PJ, Finley GA. Risk factors for pain in children with severe cognitive impairments. Dev Med Child Neurol. 2004 Jun;46(6):364-71. doi: 10.1017/s001216220400060x.</citation>
    <PMID>15174527</PMID>
  </reference>
  <reference>
    <citation>Zangen T, Ciarla C, Zangen S, Di Lorenzo C, Flores AF, Cocjin J, Reddy SN, Rowhani A, Schwankovsky L, Hyman PE. Gastrointestinal motility and sensory abnormalities may contribute to food refusal in medically fragile toddlers. J Pediatr Gastroenterol Nutr. 2003 Sep;37(3):287-93. doi: 10.1097/00005176-200309000-00016.</citation>
    <PMID>12960651</PMID>
  </reference>
  <reference>
    <citation>Hauer JM, Wical BS, Charnas L. Gabapentin successfully manages chronic unexplained irritability in children with severe neurologic impairment. Pediatrics. 2007 Feb;119(2):e519-22. doi: 10.1542/peds.2006-1609.</citation>
    <PMID>17272610</PMID>
  </reference>
  <reference>
    <citation>Breau LM, Camfield C, McGrath PJ, Rosmus C, Finley GA. Measuring pain accurately in children with cognitive impairments: refinement of a caregiver scale. J Pediatr. 2001 May;138(5):721-7. doi: 10.1067/mpd.2001.112247.</citation>
    <PMID>11343050</PMID>
  </reference>
  <reference>
    <citation>Breau LM, McGrath PJ, Camfield CS, Finley GA. Psychometric properties of the non-communicating children's pain checklist-revised. Pain. 2002 Sep;99(1-2):349-57. doi: 10.1016/s0304-3959(02)00179-3.</citation>
    <PMID>12237214</PMID>
  </reference>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>May 29, 2012</study_first_submitted>
  <study_first_submitted_qc>August 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 30, 2012</study_first_posted>
  <results_first_submitted>July 9, 2018</results_first_submitted>
  <results_first_submitted_qc>July 31, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">August 2, 2019</results_first_posted>
  <last_update_submitted>July 31, 2019</last_update_submitted>
  <last_update_submitted_qc>July 31, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 2, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>chronic irritability</keyword>
  <keyword>chronic pain</keyword>
  <keyword>Neurologically impaired</keyword>
  <keyword>gabapentin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sleep Initiation and Maintenance Disorders</mesh_term>
    <mesh_term>Chronic Pain</mesh_term>
    <mesh_term>Signs and Symptoms, Digestive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gabapentin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>April 26, 2013</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/60/NCT01675960/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 26, 2013</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/60/NCT01675960/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Gabapentin, Then Placebo</title>
          <description>Participants first receive gabapentin 3 times per day, with varying dosing based on the protocol. After 34-38 days, a washout period of 3 days occurs, before then receiving the placebo dose for 32 days.</description>
        </group>
        <group group_id="P2">
          <title>Placebo, Then Gabapentin</title>
          <description>Participants first receive placebo 3 times per day. After 34-38 days, a washout period of 3 days occurs, before then receiving Gabapentin, with varying dosing based on the protocol, for 32 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>There was no one enrolled on Placebo</population>
      <group_list>
        <group group_id="B1">
          <title>Gabapentin, Then Placebo</title>
          <description>Participants first receive gabapentin 3 times per day, with varying dosing based on the protocol. After 34-38 days, a washout period of 3 days occurs, before then receiving the placebo dose for 32 days.</description>
        </group>
        <group group_id="B2">
          <title>Placebo, Then Gabapentin</title>
          <description>Participants first receive placebo 3 times per day. After 34-38 days, a washout period of 3 days occurs, before then receiving Gabapentin, with varying dosing based on the protocol, for 32 days.</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="2"/>
            <count group_id="B2" value="0"/>
            <count group_id="B3" value="2"/>
          </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="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" 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="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" 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="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Symptom Relief for Chronic Irritability in Neurologically Impaired Children Using Gabapentin.</title>
        <description>We will determine whether gabapentin provides symptom relief for chronic irritability in neurologically impaired children, who continue to have irritability even though potential sources may have been identified and treated, or have sources that have not been identified.</description>
        <time_frame>Compiled data reviewed at completion or withdrawal from study (3 months from beginning study).</time_frame>
        <population>No one was ever enrolled in the placebo arm. The data was never analyzed for this secondary outcome. PI has left the organization therefore analysis will not occur.</population>
        <group_list>
          <group group_id="O1">
            <title>Gabapentin</title>
            <description>Neurotin&#xD;
Gabapentin: The active drug is in a flavored glycerin based solution. The drug will be given orally or through a gastrointestinal tube. Titration up to a stable dose will take 22 days. The total stable dose is 40mg/kg/day. Once 7 days on this dose are finished, children will take 6 days to reduce their dose and begin their 3 day washout period.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Glycerin based clear solution that is flavored similar to the commercial product&#xD;
placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Symptom Relief for Chronic Irritability in Neurologically Impaired Children Using Gabapentin.</title>
          <description>We will determine whether gabapentin provides symptom relief for chronic irritability in neurologically impaired children, who continue to have irritability even though potential sources may have been identified and treated, or have sources that have not been identified.</description>
          <population>No one was ever enrolled in the placebo arm. The data was never analyzed for this secondary outcome. PI has left the organization therefore analysis will not occur.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Prevalence of Associated Gastrointestinal and Sleep Problems in Neurologically Impaired Children and Improvement Using Gabapentin.</title>
        <description>We will attempt to identify gastrointestinal and sleep problems in neurologically impaired children with questionnaires given throughout the study. We hypothesize that gastrointestinal symptoms (feeding intolerance and symptoms associated with gas and bowel movements) and disrupted sleep are frequently associated with chronic irritability and will improve with gabapentin.</description>
        <time_frame>Compiled data reviewed at completion or withdrawal from study (3 months from beginning study).</time_frame>
        <population>No one was ever enrolled in the placebo arm. The data was never analyzed for this secondary outcome. PI has left the organization therefore analysis will not occur.</population>
        <group_list>
          <group group_id="O1">
            <title>Gabapentin</title>
            <description>Neurotin&#xD;
Gabapentin: The active drug is in a flavored glycerin based solution. The drug will be given orally or through a gastrointestinal tube. Titration up to a stable dose will take 22 days. The total stable dose is 40mg/kg/day. Once 7 days on this dose are finished, children will take 6 days to reduce their dose and begin their 3 day washout period.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Glycerin based clear solution that is flavored similar to the commercial product&#xD;
placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Prevalence of Associated Gastrointestinal and Sleep Problems in Neurologically Impaired Children and Improvement Using Gabapentin.</title>
          <description>We will attempt to identify gastrointestinal and sleep problems in neurologically impaired children with questionnaires given throughout the study. We hypothesize that gastrointestinal symptoms (feeding intolerance and symptoms associated with gas and bowel movements) and disrupted sleep are frequently associated with chronic irritability and will improve with gabapentin.</description>
          <population>No one was ever enrolled in the placebo arm. The data was never analyzed for this secondary outcome. PI has left the organization therefore analysis will not occur.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected during each contact with the subject after initial drug administration. Patient contacts were scheduled at day 6, 13, 24, 28, 34-37, 38, 44, 51, 62, and 76. SAE still ongoing at end of study period will be followed up on to determine final outcome.</time_frame>
      <desc>Adverse events are collection on all participants who received at least one dose of intervention, regardless of arm.</desc>
      <group_list>
        <group group_id="E1">
          <title>Gabapentin</title>
          <description>Neurotin&#xD;
Gabapentin: The active drug is in a flavored glycerin based solution. The drug will be given orally or through a gastrointestinal tube. Titration up to a stable dose will take 22 days. The total stable dose is 40mg/kg/day. Once 7 days on this dose are finished, children will take 6 days to reduce their dose and begin their 3 day washout period.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Glycerin based clear solution that is flavored similar to the commercial product&#xD;
placebo</description>
        </group>
      </group_list>
      <serious_events>
        <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="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Increased sleepiness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </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>Scott Schwantes</name_or_title>
      <organization>Children's of Minnesota</organization>
      <phone>(612)813-7888</phone>
      <email>sschwantes@gillettechildrens.com</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/NCT01675960
org study id: 112909
nct id: NCT01675960
lead sponsor: 
has dmc: Yes
This study is a prospective, randomized, double blind, placebo controlled, crossover clinical
      trial looking at whether gabapentin can provide symptom relief for chronic irritability in
      neurologically impaired children. The investigators hypothesize gabapentin ins beneficial and
      safe for children with chronic irritability that persists despite identification and
      appropriate management of symptom sources.
This is a randomized, placebo-controlled, cross-over study design of the effects of
      gabapentin on chronic irritability in neurologically impaired children. The study will
      involve a 22 day medication titration, followed by a 7 day stable dosing period and a 6 day
      medication taper period. After an additional 3 day washout period, the subject will
      cross-over to the remaining arm of the study. Subjects will be evaluated for symptoms of
      chronic pain. Since the subjects are generally non-communicative, the subjects will be
      evaluated by two questionnaires and the Non-Communicating Children's Pain Checklist-Revised,
      to be completed by their parent or primary caregiver.

      The primary aim is to determine if gabapentin provides symptom relief for chronic
      irritability in neurologically impaired children.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Symptom Relief for Chronic Irritability in Neurologically Impaired Children Using Gabapentin.
time frame: Compiled data reviewed at completion or withdrawal from study (3 months from beginning study).
description: We will determine whether gabapentin provides symptom relief for chronic irritability in neurologically impaired children, who continue to have irritability even though potential sources may have been identified and treated, or have sources that have not been identified.
measure: Prevalence of Associated Gastrointestinal and Sleep Problems in Neurologically Impaired Children and Improvement Using Gabapentin.
time frame: Compiled data reviewed at completion or withdrawal from study (3 months from beginning study).
description: We will attempt to identify gastrointestinal and sleep problems in neurologically impaired children with questionnaires given throughout the study. We hypothesize that gastrointestinal symptoms (feeding intolerance and symptoms associated with gas and bowel movements) and disrupted sleep are frequently associated with chronic irritability and will improve with gabapentin.
arm group label: Gabapentin, then placebo
arm group type: Experimental
description: Participants first receive gabapentin 3 times per day, with varying dosing based on the protocol. After 34-38 days, a washout period of 3 days occurs, before then receiving the placebo dose for 32 days.
arm group label: Placebo, then Gabapentin
arm group type: Experimental
description: Participants first receive placebo 3 times per day. After 34-38 days, a washout period of 3 days occurs, before then receiving Gabapentin, with varying dosing based on the protocol, for 32 days.
intervention type: Drug
intervention name: Gabapentin
description: The active drug is in a flavored glycerin based solution. The drug will be given orally or through a gastrointestinal tube. Titration up to a stable dose will take 22 days. The total stable dose is 40mg/kg/day. Once 7 days on this dose are finished, children will take 6 days to reduce their dose and begin their 3 day washout period.
arm group label: Gabapentin, then placebo
arm group label: Placebo, then Gabapentin
other name: Fanatrex
other name: Neurontin
other name: Gabarone
other name: Gralise
other name: Horizant
intervention type: Drug
intervention name: placebo
description: The placebo is a glycerin-based clear solution that is flavored similarly to the commercial product. The placebo will be given orally or through a gastrointestinal tube.
arm group label: Gabapentin, then placebo
arm group label: Placebo, then Gabapentin
criteria: 
gender: All
minimum age: 1 Month
maximum age: 16 Years
healthy volunteers: No
last name: Scott Schwantes, MD
role: Principal Investigator
affiliation: Gillette Children's Specialty Healthcare
facility: 
country: United States
citation: Perquin CW, Hazebroek-Kampschreur AAJM, Hunfeld JAM, Bohnen AM, van Suijlekom-Smit LWA, Passchier J, van der Wouden JC. Pain in children and adolescents: a common experience. Pain. 2000 Jul;87(1):51-58. doi: 10.1016/S0304-3959(00)00269-4.
PMID: 10863045
citation: Breau LM, Camfield CS, McGrath PJ, Finley GA. The incidence of pain in children with severe cognitive impairments. Arch Pediatr Adolesc Med. 2003 Dec;157(12):1219-26. doi: 10.1001/archpedi.157.12.1219.
PMID: 14662579
citation: Houlihan CM, O'Donnell M, Conaway M, Stevenson RD. Bodily pain and health-related quality of life in children with cerebral palsy. Dev Med Child Neurol. 2004 May;46(5):305-10. doi: 10.1017/s0012162204000507.
PMID: 15132260
citation: Stallard P, Williams L, Lenton S, Velleman R. Pain in cognitively impaired, non-communicating children. Arch Dis Child. 2001 Dec;85(6):460-2. doi: 10.1136/adc.85.6.460.
PMID: 11719327
citation: Greco C, Berde C. Pain management for the hospitalized pediatric patient. Pediatr Clin North Am. 2005 Aug;52(4):995-1027, vii-viii. doi: 10.1016/j.pcl.2005.04.005.
PMID: 16009254
citation: Breau LM, Camfield CS, McGrath PJ, Finley GA. Risk factors for pain in children with severe cognitive impairments. Dev Med Child Neurol. 2004 Jun;46(6):364-71. doi: 10.1017/s001216220400060x.
PMID: 15174527
citation: Zangen T, Ciarla C, Zangen S, Di Lorenzo C, Flores AF, Cocjin J, Reddy SN, Rowhani A, Schwankovsky L, Hyman PE. Gastrointestinal motility and sensory abnormalities may contribute to food refusal in medically fragile toddlers. J Pediatr Gastroenterol Nutr. 2003 Sep;37(3):287-93. doi: 10.1097/00005176-200309000-00016.
PMID: 12960651
citation: Hauer JM, Wical BS, Charnas L. Gabapentin successfully manages chronic unexplained irritability in children with severe neurologic impairment. Pediatrics. 2007 Feb;119(2):e519-22. doi: 10.1542/peds.2006-1609.
PMID: 17272610
citation: Breau LM, Camfield C, McGrath PJ, Rosmus C, Finley GA. Measuring pain accurately in children with cognitive impairments: refinement of a caregiver scale. J Pediatr. 2001 May;138(5):721-7. doi: 10.1067/mpd.2001.112247.
PMID: 11343050
citation: Breau LM, McGrath PJ, Camfield CS, Finley GA. Psychometric properties of the non-communicating children's pain checklist-revised. Pain. 2002 Sep;99(1-2):349-57. doi: 10.1016/s0304-3959(02)00179-3.
PMID: 12237214
responsible party type: Sponsor
mesh term: Sleep Initiation and Maintenance Disorders
mesh term: Chronic Pain
mesh term: Signs and Symptoms, Digestive
mesh term: Gabapentin
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 