<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/NCT01733680</url>
  </required_header>
  <id_info>
    <org_study_id>320969</org_study_id>
    <nct_id>NCT01733680</nct_id>
  </id_info>
  <brief_title>Amiloride Hydrochloride as an Effective Treatment for ADHD</brief_title>
  <official_title>Amiloride Hydrochloride as an Effective Treatment for ADHD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>State University of New York - Upstate Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>State University of New York - Upstate Medical University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators are proposing to test a medication derived from our prior studies of the&#xD;
      gene SLC9A9. This one gene makes NHE proteins that control how we learn and remember items,&#xD;
      which is impaired in ADHD and may cause an inability to plan, prioritize,&#xD;
      self-monitor,inhibit, initiate, self-correct, or control one's behavior. The investigators&#xD;
      now propose to investigate the therapeutic utility of an NHE inhibitor, amiloride&#xD;
      hydrochloride, for the treatment of attention deficit hyperactivity disorder (ADHD) in&#xD;
      medication-naïve adults with ADHD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Our specific aims and hypotheses are as follows:&#xD;
&#xD;
      Primary Aim: Assess the efficacy and adverse effects of amiloride in medication naive ADHD&#xD;
      adults in a placebo controlled study. Hypothesis 1: Amiloride will reduce scores on our&#xD;
      primary outcome measure, the Adult Attention-Deficit/Hyperactivity Disorder Investigator&#xD;
      Symptom Rating Scale (AISRS) and on our secondary outcome, the ADHD specific Clinical Global&#xD;
      Impressions (CGI) improvement scale. Hypothesis 2: Amiloride will be well tolerated and will&#xD;
      have few side effects in adults with ADHD.&#xD;
&#xD;
      Exploratory Aim 2: Assess effects of amiloride on ADHD-associated clinical features. We will&#xD;
      also assess, in an exploratory manner, the effect of amiloride on two clinical features that&#xD;
      are not well treated by current ADHD medications: deficits in emotional self-regulation&#xD;
      (DESR) and executive function deficit (EFD). Hypothesis 3 predicts that amiloride treatment&#xD;
      will reduce symptoms of DESR and of EFD.&#xD;
&#xD;
      We will recruit 40 adults who are diagnosed with ADHD in a double blind placebo controlled&#xD;
      study. 20 subjects will receive amiloride hydrochloride and 20 subjects will receive placebo&#xD;
      for 8 weeks. Participation in the study requires subjects to meet with the physician for a&#xD;
      screening visit, baseline visit and 8 additional weekly visits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study stopped due to lack of recruitment&#xD;
  </why_stopped>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">September 2015</completion_date>
  <primary_completion_date type="Actual">September 2015</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Improvement in CGI</measure>
    <time_frame>8 weeks</time_frame>
    <description>CGI Improvement scale: 1=very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>AISRS, Adult ADHD Investigator Rating Scale</measure>
    <time_frame>8 weeks</time_frame>
    <description>An 18 item clinician administered questionnaire to evaluate ADHD in adults. Responses to questions were 0-None, 1-Mild, 2-Moderate, 3-Severe. A decrease of 30% in the total score would be considered improvement. Total score range is 0-54. A lower score indicates improvement in symptoms. A score of 24 or more indicates symptomatic ADHD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A)</measure>
    <time_frame>8 weeks</time_frame>
    <description>BRIEF-A is a 75 item self report questionnaire that measures behavior and executive function. For each item the subject is asked &quot;during the past month, how often has each of the following behaviors been a problem?:&quot; The choices are N (never), S (sometimes), O (Often). Total score for the Global Executive Composite used. Raw data were transformed into t-scores, which are standardized scores that indicate the number of standard deviations away from the mean. A T-score of 50 is equal to the mean. Values less than 65 indicate executive function is not a problem and values greater than 65 indicate executive function is often a problem.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>ADHD</condition>
  <arm_group>
    <arm_group_label>Amiloride</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Drug: Subjects will take 5mg qd Amiloride for 2 weeks, 10mg qd Amiloride for 3 weeks, 15 mg qd Amiloride for 3 weeks.&#xD;
Behavioral: Each week subjects will complete the AISRS, BRIEF-A, and CGI.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Drug: Subjects will take placebo for 8 weeks Behavioral: Each week subjects will complete questionnaires: AISRS, BRIEF-A, and CGI</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>amiloride</intervention_name>
    <description>Subjects will take either amiloride hydrochloride or placebo for 8 weeks.</description>
    <arm_group_label>Amiloride</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Behavioral</intervention_name>
    <description>Each week of the study, subjects will complete the AISRS, BRIEF-A, and CGI to measure symptom improvement</description>
    <arm_group_label>Amiloride</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>ADHD symptoms, executive function, emotional self-regulation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Medication naïve male or female adults ages 18-55 years.&#xD;
&#xD;
          2. A diagnosis of DSM-IV ADHD combined type based on clinical assessment by the study&#xD;
             psychiatrist using the Conners Adult ADHD Diagnostic Interview;&#xD;
&#xD;
          3. proficiency in English;&#xD;
&#xD;
          4. A baseline score of 24 or more on the AISRS;&#xD;
&#xD;
          5. ability to swallow pills;&#xD;
&#xD;
          6. ability to report reliably, understand the nature of the study and sign an informed&#xD;
             consent document as determined by the study psychiatrist&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        We will exclude potential participants who:&#xD;
&#xD;
          1. have had pharmacologic treatment for ADHD in the past year;&#xD;
&#xD;
          2. are pregnant or nursing;&#xD;
&#xD;
          3. are Investigators or their immediate family (spouse, parent, child, grandparent, or&#xD;
             grandchild);&#xD;
&#xD;
          4. have any serious, unstable medical illness including hepatic, renal,&#xD;
             gastroenterological, respiratory, cardiovascular (including ischemic heart disease),&#xD;
             endocrinologic, neurologic, immunologic, or hematologic disease;&#xD;
&#xD;
          5. have severe allergies or multiple adverse drug reactions;&#xD;
&#xD;
          6. have a current or past history of seizures;&#xD;
&#xD;
          7. meet current DSM-IV criteria for anxiety or depression or illicit substance abuse in&#xD;
             prior six months (these exclusions are feasible because, although the lifetime&#xD;
             comorbidity of ADHD with these disorders is high, we and others have shown that the&#xD;
             presence of these disorders at the time of ascertainment for adult ADHD studies is&#xD;
             less than 10%);&#xD;
&#xD;
          8. are judged by the study psychiatrist to be at serious suicidal risk.&#xD;
&#xD;
          9. have current or past diagnoses of schizophrenia or bipolar disorder;&#xD;
&#xD;
         10. have a history of hypersensitivity to amiloride or drug class members;&#xD;
&#xD;
         11. have a history of hyperkalemia, diabetes mellitus, renal disease or anuria;&#xD;
&#xD;
         12. have renal impairment Cr &gt; 1.5; or&#xD;
&#xD;
         13. are taking potassium supplements, aldosterone antagonists, tacrolimus or ACE&#xD;
             inhibitors.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stephen V Faraone, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>SUNY Upstate Medical Unversity</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Prashant Kaul, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>VA Medical Center at Syracuse</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>SUNY Upstate Medical University</name>
      <address>
        <city>Syracuse</city>
        <state>New York</state>
        <zip>13210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>November 20, 2012</study_first_submitted>
  <study_first_submitted_qc>November 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 27, 2012</study_first_posted>
  <results_first_submitted>December 30, 2015</results_first_submitted>
  <results_first_submitted_qc>October 6, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">July 20, 2018</results_first_posted>
  <last_update_submitted>October 6, 2017</last_update_submitted>
  <last_update_submitted_qc>October 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ADHD</keyword>
  <keyword>executive function</keyword>
  <keyword>emotional self-regulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Attention Deficit Disorder with Hyperactivity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amiloride</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subjects were recruited via a medical clinic and outside advertisement. Due to the stringent inclusion/exclusion criteria, we were only able to recruit 3 subjects and the physician who was conducting the study chose not to continue and we were unable to find another physician.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Amiloride</title>
          <description>Drug: Subjects will take 5mg qd Amiloride for 2 weeks, 10mg qd Amiloride for 3 weeks, 15 mg qd Amiloride for 3 weeks.&#xD;
Behavioral: Each week subjects will complete the AISRS, BRIEF-A, and CGI.&#xD;
amiloride: Subjects will take either amiloride hydrochloride or placebo for 8 weeks.&#xD;
Behavioral: Each week of the study, subjects will complete the AISRS, BRIEF-A, and CGI to measure symptom improvement</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Drug: Subjects will take placebo for 8 weeks Behavioral: Each week subjects will complete questionnaires: AISRS, BRIEF-A, and CGI&#xD;
Behavioral: Each week of the study, subjects will complete the AISRS, BRIEF-A, and CGI to measure symptom improvement</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="1"/>
              </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="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Arm 1-Amiloride</title>
          <description>Subjects received amiloride hydrochloride (5 mg for 2 weeks, 10 mg for 3 week, and 15 mg for 3 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Arm 2-Placebo</title>
          <description>Subjects received placebo for 8 weeks.</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="1"/>
            <count group_id="B3" value="3"/>
          </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="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</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>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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>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="B2" 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="B2" 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="B2" 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="B2" 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="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>Unknown or Not Reported</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>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>CGI</title>
          <description>Clinical Global Impressions (CGI)&#xD;
Normal, not at all ill&#xD;
Borderline mentally ill&#xD;
Mildly ill&#xD;
Moderately ill&#xD;
Markedly ill&#xD;
Severely ill&#xD;
Among the most extremely ill patients</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.0" lower_limit="4.0" upper_limit="4.0"/>
                    <measurement group_id="B2" value="5" lower_limit="5" upper_limit="5"/>
                    <measurement group_id="B3" value="4.33" lower_limit="4" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Improvement in CGI</title>
        <description>CGI Improvement scale: 1=very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse</description>
        <time_frame>8 weeks</time_frame>
        <population>There was no statistical analysis done due to the small number of participants in the study</population>
        <group_list>
          <group group_id="O1">
            <title>Amiloride</title>
            <description>Drug: Subjects will take 5mg qd Amiloride for 2 weeks, 10mg qd Amiloride for 3 weeks, 15 mg qd Amiloride for 3 weeks.&#xD;
Behavioral: Each week subjects will complete the AISRS, BRIEF-A, and CGI.&#xD;
amiloride: Subjects will take either amiloride hydrochloride or placebo for 8 weeks.&#xD;
Behavioral: Each week of the study, subjects will complete the AISRS, BRIEF-A, and CGI to measure symptom improvement</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Drug: Subjects will take placebo for 8 weeks Behavioral: Each week subjects will complete questionnaires: AISRS, BRIEF-A, and CGI&#xD;
Behavioral: Each week of the study, subjects will complete the AISRS, BRIEF-A, and CGI to measure symptom improvement</description>
          </group>
        </group_list>
        <measure>
          <title>Improvement in CGI</title>
          <description>CGI Improvement scale: 1=very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse</description>
          <population>There was no statistical analysis done due to the small number of participants in the study</population>
          <units>Units on a scale</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>CGI Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" lower_limit="4" upper_limit="4"/>
                    <measurement group_id="O2" value="5" lower_limit="5" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CGI Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" lower_limit="4" upper_limit="4"/>
                    <measurement group_id="O2" value="3" lower_limit="3" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CGI Week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" lower_limit="4" upper_limit="4"/>
                    <measurement group_id="O2" value="5" lower_limit="5" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CGI Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5" lower_limit="3" upper_limit="4"/>
                    <measurement group_id="O2" value="5" lower_limit="5" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CGI Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" lower_limit="4" upper_limit="4"/>
                    <measurement group_id="O2" value="5" lower_limit="5" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CGI Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5" lower_limit="3" upper_limit="4"/>
                    <measurement group_id="O2" value="5" lower_limit="5" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CGI Week 9</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5" lower_limit="3" upper_limit="4"/>
                    <measurement group_id="O2" value="5" lower_limit="5" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CGI Week 10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5" lower_limit="3" upper_limit="4"/>
                    <measurement group_id="O2" value="5" lower_limit="5" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AISRS, Adult ADHD Investigator Rating Scale</title>
        <description>An 18 item clinician administered questionnaire to evaluate ADHD in adults. Responses to questions were 0-None, 1-Mild, 2-Moderate, 3-Severe. A decrease of 30% in the total score would be considered improvement. Total score range is 0-54. A lower score indicates improvement in symptoms. A score of 24 or more indicates symptomatic ADHD.</description>
        <time_frame>8 weeks</time_frame>
        <population>Statistical analysis of the outcome data was not done due to the small N.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1-Amiloride</title>
            <description>Amiloride was administered for 8 weeks. 5 mg for 2 weeks, 10 mg for 3 weeks and 15 mg for 3 weeks</description>
          </group>
          <group group_id="O2">
            <title>Arm 2-Placebo</title>
            <description>Subjects were given placebo for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>AISRS, Adult ADHD Investigator Rating Scale</title>
          <description>An 18 item clinician administered questionnaire to evaluate ADHD in adults. Responses to questions were 0-None, 1-Mild, 2-Moderate, 3-Severe. A decrease of 30% in the total score would be considered improvement. Total score range is 0-54. A lower score indicates improvement in symptoms. A score of 24 or more indicates symptomatic ADHD.</description>
          <population>Statistical analysis of the outcome data was not done due to the small N.</population>
          <units>Total score</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39" lower_limit="30" upper_limit="48"/>
                    <measurement group_id="O2" value="54" lower_limit="54" upper_limit="54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.5" lower_limit="29" upper_limit="48"/>
                    <measurement group_id="O2" value="51" lower_limit="51" upper_limit="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.5" lower_limit="18" upper_limit="47"/>
                    <measurement group_id="O2" value="50" lower_limit="50" upper_limit="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31" lower_limit="20" upper_limit="42"/>
                    <measurement group_id="O2" value="50" lower_limit="50" upper_limit="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31" lower_limit="17" upper_limit="45"/>
                    <measurement group_id="O2" value="50" lower_limit="50" upper_limit="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34" lower_limit="19" upper_limit="49"/>
                    <measurement group_id="O2" value="50" lower_limit="50" upper_limit="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 9</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26" lower_limit="14" upper_limit="38"/>
                    <measurement group_id="O2" value="50" lower_limit="50" upper_limit="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.5" lower_limit="20" upper_limit="45"/>
                    <measurement group_id="O2" value="50" lower_limit="50" upper_limit="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A)</title>
        <description>BRIEF-A is a 75 item self report questionnaire that measures behavior and executive function. For each item the subject is asked &quot;during the past month, how often has each of the following behaviors been a problem?:&quot; The choices are N (never), S (sometimes), O (Often). Total score for the Global Executive Composite used. Raw data were transformed into t-scores, which are standardized scores that indicate the number of standard deviations away from the mean. A T-score of 50 is equal to the mean. Values less than 65 indicate executive function is not a problem and values greater than 65 indicate executive function is often a problem.</description>
        <time_frame>8 weeks</time_frame>
        <population>Statistical analysis of the outcome data was not done due to the small N of each group</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1-Amiloride</title>
            <description>Subjects received amiloride hydrochloride for 8 weeks. 5 mg/day for 2 weeks, 10 mg/day for 3 weeks, and 15 mg/day for 3 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2-Placebo</title>
            <description>Subjects received placebo for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A)</title>
          <description>BRIEF-A is a 75 item self report questionnaire that measures behavior and executive function. For each item the subject is asked &quot;during the past month, how often has each of the following behaviors been a problem?:&quot; The choices are N (never), S (sometimes), O (Often). Total score for the Global Executive Composite used. Raw data were transformed into t-scores, which are standardized scores that indicate the number of standard deviations away from the mean. A T-score of 50 is equal to the mean. Values less than 65 indicate executive function is not a problem and values greater than 65 indicate executive function is often a problem.</description>
          <population>Statistical analysis of the outcome data was not done due to the small N of each group</population>
          <units>Global Executive Composite T Score</units>
          <param>Mean</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.5" lower_limit="63.5" upper_limit="69.5"/>
                    <measurement group_id="O2" value="95" lower_limit="92" upper_limit="98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.5" lower_limit="67.5" upper_limit="73.5"/>
                    <measurement group_id="O2" value="92" lower_limit="89" upper_limit="95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68" lower_limit="65" upper_limit="71"/>
                    <measurement group_id="O2" value="96" lower_limit="93" upper_limit="99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.5" lower_limit="65.5" upper_limit="71.5"/>
                    <measurement group_id="O2" value="96" lower_limit="93" upper_limit="99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.5" lower_limit="59.5" upper_limit="65.5"/>
                    <measurement group_id="O2" value="96" lower_limit="93" upper_limit="99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.5" lower_limit="59.5" upper_limit="65.5"/>
                    <measurement group_id="O2" value="96" lower_limit="93" upper_limit="99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 9</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.5" lower_limit="59.5" upper_limit="65.5"/>
                    <measurement group_id="O2" value="96" lower_limit="93" upper_limit="99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62" lower_limit="59" upper_limit="65"/>
                    <measurement group_id="O2" value="96" lower_limit="93" upper_limit="99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>10 weeks</time_frame>
      <desc>Adverse events that were monitored was blood pressure, weight, heart rate, EKG, CBC, TSH, lipid profile, BMP, general malaise, tiredness, headache.</desc>
      <group_list>
        <group group_id="E1">
          <title>Amiloride</title>
          <description>Drug: Subjects will take 5mg qd Amiloride for 2 weeks, 10mg qd Amiloride for 3 weeks, 15 mg qd Amiloride for 3 weeks.&#xD;
Behavioral: Each week subjects will complete the AISRS, BRIEF-A, and CGI.&#xD;
amiloride: Subjects will take either amiloride hydrochloride or placebo for 8 weeks.&#xD;
Behavioral: Each week of the study, subjects will complete the AISRS, BRIEF-A, and CGI to measure symptom improvement</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Drug: Subjects will take placebo for 8 weeks Behavioral: Each week subjects will complete questionnaires: AISRS, BRIEF-A, and CGI&#xD;
Behavioral: Each week of the study, subjects will complete the AISRS, BRIEF-A, and CGI to measure symptom improvement</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <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="1"/>
              </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="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </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>
    <limitations_and_caveats>Because of the low number of subjects enrolled in the study, no outcome measures were statistically analyzed.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Gail P DePalma</name_or_title>
      <organization>SUNy Upstate Medical University</organization>
      <phone>3154643260</phone>
      <email>depalmag@upstate.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/NCT01733680
org study id: 320969
nct id: NCT01733680
lead sponsor: 
has dmc: Yes
The investigators are proposing to test a medication derived from our prior studies of the
      gene SLC9A9. This one gene makes NHE proteins that control how we learn and remember items,
      which is impaired in ADHD and may cause an inability to plan, prioritize,
      self-monitor,inhibit, initiate, self-correct, or control one's behavior. The investigators
      now propose to investigate the therapeutic utility of an NHE inhibitor, amiloride
      hydrochloride, for the treatment of attention deficit hyperactivity disorder (ADHD) in
      medication-naïve adults with ADHD.
Our specific aims and hypotheses are as follows:

      Primary Aim: Assess the efficacy and adverse effects of amiloride in medication naive ADHD
      adults in a placebo controlled study. Hypothesis 1: Amiloride will reduce scores on our
      primary outcome measure, the Adult Attention-Deficit/Hyperactivity Disorder Investigator
      Symptom Rating Scale (AISRS) and on our secondary outcome, the ADHD specific Clinical Global
      Impressions (CGI) improvement scale. Hypothesis 2: Amiloride will be well tolerated and will
      have few side effects in adults with ADHD.

      Exploratory Aim 2: Assess effects of amiloride on ADHD-associated clinical features. We will
      also assess, in an exploratory manner, the effect of amiloride on two clinical features that
      are not well treated by current ADHD medications: deficits in emotional self-regulation
      (DESR) and executive function deficit (EFD). Hypothesis 3 predicts that amiloride treatment
      will reduce symptoms of DESR and of EFD.

      We will recruit 40 adults who are diagnosed with ADHD in a double blind placebo controlled
      study. 20 subjects will receive amiloride hydrochloride and 20 subjects will receive placebo
      for 8 weeks. Participation in the study requires subjects to meet with the physician for a
      screening visit, baseline visit and 8 additional weekly visits.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Improvement in CGI
time frame: 8 weeks
description: CGI Improvement scale: 1=very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse
measure: AISRS, Adult ADHD Investigator Rating Scale
time frame: 8 weeks
description: An 18 item clinician administered questionnaire to evaluate ADHD in adults. Responses to questions were 0-None, 1-Mild, 2-Moderate, 3-Severe. A decrease of 30% in the total score would be considered improvement. Total score range is 0-54. A lower score indicates improvement in symptoms. A score of 24 or more indicates symptomatic ADHD.
measure: The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A)
time frame: 8 weeks
description: BRIEF-A is a 75 item self report questionnaire that measures behavior and executive function. For each item the subject is asked "during the past month, how often has each of the following behaviors been a problem?:" The choices are N (never), S (sometimes), O (Often). Total score for the Global Executive Composite used. Raw data were transformed into t-scores, which are standardized scores that indicate the number of standard deviations away from the mean. A T-score of 50 is equal to the mean. Values less than 65 indicate executive function is not a problem and values greater than 65 indicate executive function is often a problem.
arm group label: Amiloride
arm group type: Active Comparator
description: Drug: Subjects will take 5mg qd Amiloride for 2 weeks, 10mg qd Amiloride for 3 weeks, 15 mg qd Amiloride for 3 weeks.
Behavioral: Each week subjects will complete the AISRS, BRIEF-A, and CGI.
arm group label: Placebo
arm group type: Placebo Comparator
description: Drug: Subjects will take placebo for 8 weeks Behavioral: Each week subjects will complete questionnaires: AISRS, BRIEF-A, and CGI
intervention type: Drug
intervention name: amiloride
description: Subjects will take either amiloride hydrochloride or placebo for 8 weeks.
arm group label: Amiloride
intervention type: Behavioral
intervention name: Behavioral
description: Each week of the study, subjects will complete the AISRS, BRIEF-A, and CGI to measure symptom improvement
arm group label: Amiloride
arm group label: Placebo
other name: ADHD symptoms, executive function, emotional self-regulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Stephen V Faraone, PhD
role: Principal Investigator
affiliation: SUNY Upstate Medical Unversity
last name: Prashant Kaul, MD
role: Principal Investigator
affiliation: VA Medical Center at Syracuse
facility: 
country: United States
responsible party type: Sponsor
mesh term: Attention Deficit Disorder with Hyperactivity
mesh term: Amiloride
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Because of the low number of subjects enrolled in the study, no outcome measures were statistically analyzed.
point of contact: 