<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/NCT01695317</url>
  </required_header>
  <id_info>
    <org_study_id>2012-001624-36</org_study_id>
    <nct_id>NCT01695317</nct_id>
  </id_info>
  <brief_title>Effect of Acetyl-L-carnitine in Migraine</brief_title>
  <acronym>ALCAR</acronym>
  <official_title>Effect of Acetyl-L-carnitine in Migraine - a Randomized, Double-blind Placebo Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Norwegian University of Science and Technology</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Norwegian University of Science and Technology</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Traditionally, beta blockers have been used for migraine prophylaxis, but in later years also&#xD;
      antiepileptic drugs. Contraindications and side effects have to some degree limited their&#xD;
      use, and new prophylactics that can be used by most migraine sufferers and with little side&#xD;
      effects are in demand. One product that may seem to fulfill these requirements is&#xD;
      Acetyl-L-carnitine, which is a dietary supplement and naturally occurs in plants and animals.&#xD;
      L-carnitine is necessary for fatty-acid metabolism and energy production.&#xD;
&#xD;
      To our knowledge, no placebo-controlled studies have previously evaluated the efficacy of&#xD;
      Acetyl-L-carnitine in adults with migraine.&#xD;
&#xD;
      The aims of the present study is to evaluate the efficacy of Acetyl-L-carnitine as a&#xD;
      prophylaxis in migraine patients&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will be a single-centre double-blinded, randomized, placebo controlled crossover&#xD;
      study with Acetyl-L-carnitine or placebo. We plan to include 72 patients. The follow up&#xD;
      duration will be 36 weeks. The study will be performed according to Good Clinical Practice,&#xD;
      and relying partly on the International Headache Society Guidelines for controlled trials of&#xD;
      drugs in migraine from 2012 and partly on the guidelines divulged by the International&#xD;
      Headache Society task force on trial guidelines for chronic migraine.&#xD;
&#xD;
      After a screening visit including a neurological consultation, eligible patients will sign an&#xD;
      informed consent declaration before they enter a 4 week run-in (baseline) period when they&#xD;
      keep a headache diary. After 4 weeks they return for the second visit. If they have had 2 or&#xD;
      more migraine attacks they are allowed to proceed in the study. If they have less than 2&#xD;
      migraine attacks (required for proceeding in the study), they are allowed to extend the&#xD;
      baseline period another 4 weeks. Those who then during the whole 8 week period have on&#xD;
      average 2 or more migraine attacks per month are also allowed to proceed. Otherwise they are&#xD;
      excluded from the study.&#xD;
&#xD;
      Details of the treatment period The duration of each of the two treatment periods is 12&#xD;
      weeks. During each period there will be one telephone contact at the start of each treatment&#xD;
      period to remind patients to start with medicines, and one after 2 weeks to check compliance&#xD;
      and side effects. In the second last week of every treatment period there will be a doctor&#xD;
      and nurse visit with drug accounting and dispensing of new medicines for the next period. At&#xD;
      this visit one will ensure that the patient has just enough medicines left to finish the&#xD;
      period before the wash-out. As recommended in crossover studies, the participants enter a&#xD;
      washout period of 4 weeks between the two treatment periods, to reduce the risk of carryover&#xD;
      effect.&#xD;
&#xD;
      Randomization Randomization will be generated using a computerized procedure. A randomization&#xD;
      list containing 72 patient numbers is made before the start of the study, and the patient&#xD;
      number is then indicated on a package with medicines for that patient. The study has a&#xD;
      crossover design, and the two different treatment periods (active or placebo) can arise to&#xD;
      two different treatment sequences (AP or PA). Patients are therefore randomized in blocks of&#xD;
      4 where one of these two treatment sequences is assigned to each patient in random order.&#xD;
      With 72 patients to be included, this means that 18 patients are randomized in each block. In&#xD;
      each block, 50% patients have the treatment sequence AP, and 50% PA in a random order.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2013</start_date>
  <completion_date type="Actual">September 2014</completion_date>
  <primary_completion_date type="Actual">July 2014</primary_completion_date>
  <phase>Phase 4</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Headache Days</measure>
    <time_frame>last 4 weeks</time_frame>
    <description>The number of days per 4 weeks with moderate or severe headache lasting ≥ 4 hours or if treated with the patient's usual headache medication (usually a triptan) as the primary endpoint.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Days With Migraine and Side Effects</measure>
    <time_frame>Last 4 weeks</time_frame>
    <description>Secondary measures will be: Days with migraine; days with headache; hours with headache; headache intensity (0-3 scale) on days with headache; doses of analgesics; doses of triptans; days with sick leave; number of responders (≥ 50% decrease in migraine days compared with baseline); incidence of side effects recorded openly.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>Migraine</condition>
  <arm_group>
    <arm_group_label>Acetyl-L-carnitine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Acetyl-L-carnitine tablets</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sugar pills</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Glucose with lemon acid</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acetyl-L-carnitine</intervention_name>
    <description>Week 1: 500 mg x 3, Week 2-12: 500 mg x 6</description>
    <arm_group_label>Acetyl-L-carnitine</arm_group_label>
    <arm_group_label>Sugar pills</arm_group_label>
    <other_name>ALCAR</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 to 65 years&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
          -  Migraine with or without aura according to International Classification of Headache&#xD;
             Disorders, second version (ICHD-2) criteria&#xD;
&#xD;
          -  chronic migraine according to the ICHD-2 criteria (revision 1)&#xD;
&#xD;
          -  Retrospectively have 2 or more migraine attacks per month during the last 3 month&#xD;
&#xD;
          -  During the baseline period have 2 or more migraine attacks&#xD;
&#xD;
          -  Debut of migraine at least one year prior to inclusion&#xD;
&#xD;
          -  Start of migraine before age 50 years&#xD;
&#xD;
          -  Body mass index (BMI )between 18-35 kg/m2&#xD;
&#xD;
          -  No medication overuse during the last 3 months defined as headache &gt;14 days/month&#xD;
             combined with overuse simple analgesics &gt;14 days/month or triptans or combined&#xD;
             medications ≥ 10 days/month.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Interval headache not distinguishable from migraine&#xD;
&#xD;
          -  Chronic tension-type headache or other headache than migraine occurring on ≥ 15&#xD;
             days/month with or without medication overuse&#xD;
&#xD;
          -  Pregnancy, nursing or inability to use contraceptives&#xD;
&#xD;
          -  Hypersensitivity to active substance&#xD;
&#xD;
          -  History of angioneurotic edema, diabetes mellitus, significant psychiatric illness&#xD;
             and/or Hospital anxiety and Depression Scale( HADS) anxiety score ≥ 11 or HADS&#xD;
             depression score ≥ 11, and/or use of selective serotonin reuptake inhibitors (SSRI),&#xD;
             antipsychotic medication, or antidepressant medication during the last 3 months&#xD;
&#xD;
          -  Use of daily migraine prophylactics less than 3 months prior to start of study&#xD;
&#xD;
          -  Previous use of Acetyl-L-carnitine&#xD;
&#xD;
          -  BMI &lt;18 kg/m2 or BMI &gt; 35 kg/m2&#xD;
&#xD;
          -  Having tried ≥ 3 prophylactic drugs against migraine during the last 5 years&#xD;
&#xD;
          -  Subjects requiring detoxification from acute medication&#xD;
&#xD;
          -  Patients who consistently fail to respond to any acute migraine medication&#xD;
&#xD;
          -  Patients with alcohol or illicit drug dependence; 13) Subjects with renal disease or&#xD;
             decreased renal function&#xD;
&#xD;
          -  Previous or present history of asthma or vascular disease, arterial claudication&#xD;
             included.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Knut Hagen, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Norwegian National Headache Centre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Norwegian National Headache Centre</name>
      <address>
        <city>Trondheim</city>
        <zip>7489</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <results_reference>
    <citation>Hagen K, Brenner E, Linde M, Gravdahl GB, Tronvik EA, Engstrom M, Sonnewald U, Helde G, Stovner LJ, Sand T. Acetyl-l-carnitine versus placebo for migraine prophylaxis: A randomized, triple-blind, crossover study. Cephalalgia. 2015 Oct;35(11):987-95. doi: 10.1177/0333102414566817. Epub 2015 Jan 19.</citation>
    <PMID>25601916</PMID>
  </results_reference>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>September 24, 2012</study_first_submitted>
  <study_first_submitted_qc>September 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 27, 2012</study_first_posted>
  <results_first_submitted>October 26, 2021</results_first_submitted>
  <results_first_submitted_qc>February 15, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">April 13, 2022</results_first_posted>
  <last_update_submitted>February 15, 2022</last_update_submitted>
  <last_update_submitted_qc>February 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Migraine</keyword>
  <keyword>Preventive medication</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Migraine Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetylcarnitine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Acetyl-L-carnitine First, Then Sugar Pills</title>
          <description>Period 1: Acetyl-L-carnitine tablets Week 1: 500 mg x 3 (1.5 g), Week 2-12: 500 mg x 6 (3.0 g) Period 2: Sugar tablets (500 mg dextrose and citric acid): Week 1: 1 tablet x 3 (1,5 g), week 2-12: 6 tablets (3.0 g)</description>
        </group>
        <group group_id="P2">
          <title>Sugar Pills First, Then Acetyl-L-carnitine</title>
          <description>Period 1:&#xD;
Sugar tablets (500 mg dextrose and citric acid): Week 1: 1 tablet x 3 (1,5 g), week 2-12: 6 tablets (3.0 g) Period 2: Acetyl-L-carnitine: Week 1: 500 mg x 3 (1.5 g), Week 2-12: 500 mg x 6 (3.0 g)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1 in the Cross-over Design</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
                <participants group_id="P2" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
                <participants group_id="P2" count="35"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <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="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Cross-over to Period 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
                <participants group_id="P2" count="35"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="34"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="34"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Acetyl-L-carnitine First, Then Sugar Pills</title>
          <description>Period 1: Acetyl-L-carnitine tablets Acetyl-L-carnitine: Week 1: 500 mg x 3, Week 2-12: 500 mg x 6&#xD;
Period 2: Glucose with lemon acid Sugar pills Week 1: 500 mg x 3, Week 2-12: 500 mg x 6</description>
        </group>
        <group group_id="B2">
          <title>Sugar Pills First, Then Acetyl-L-carnitine</title>
          <description>Period 1: Glucose with lemon acid Sugar pills Week 1: 500 mg x 3, Week 2-12: 500 mg x 6&#xD;
Period 2: Acetyl-L-carnitine tablets Acetyl-L-carnitine: Week 1: 500 mg x 3, Week 2-12: 500 mg x 6</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="36"/>
            <count group_id="B2" value="36"/>
            <count group_id="B3" value="72"/>
          </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="36"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="72"/>
                  </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>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39" spread="14"/>
                    <measurement group_id="B2" value="39" spread="14"/>
                    <measurement group_id="B3" value="39" spread="14"/>
                  </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="23"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="46"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="26"/>
                  </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>Norway</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Headache Days</title>
        <description>The number of days per 4 weeks with moderate or severe headache lasting ≥ 4 hours or if treated with the patient's usual headache medication (usually a triptan) as the primary endpoint.</description>
        <time_frame>last 4 weeks</time_frame>
        <population>Headache days per four week</population>
        <group_list>
          <group group_id="O1">
            <title>Acetyl-L-carnitine</title>
            <description>Acetyl-L-carnitine tablets&#xD;
Acetyl-L-carnitine: Week 1: 500 mg x 3, Week 2-12: 500 mg x 6</description>
          </group>
          <group group_id="O2">
            <title>Sugar Pills</title>
            <description>Glucose with lemon acid&#xD;
Acetyl-L-carnitine: Week 1: 500 mg x 3, Week 2-12: 500 mg x 6</description>
          </group>
        </group_list>
        <measure>
          <title>Headache Days</title>
          <description>The number of days per 4 weeks with moderate or severe headache lasting ≥ 4 hours or if treated with the patient's usual headache medication (usually a triptan) as the primary endpoint.</description>
          <population>Headache days per four week</population>
          <units>Headache days per 4 weeks</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="72"/>
                <count group_id="O2" value="72"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.1" spread="2.8"/>
                    <measurement group_id="O2" value="5.2" spread="3.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Days With Migraine and Side Effects</title>
        <description>Secondary measures will be: Days with migraine; days with headache; hours with headache; headache intensity (0-3 scale) on days with headache; doses of analgesics; doses of triptans; days with sick leave; number of responders (≥ 50% decrease in migraine days compared with baseline); incidence of side effects recorded openly.</description>
        <time_frame>Last 4 weeks</time_frame>
        <population>Headache hours per 4 weeks</population>
        <group_list>
          <group group_id="O1">
            <title>Acetyl-L-carnitine</title>
            <description>Acetyl-L-carnitine tablets&#xD;
Acetyl-L-carnitine: Week 1: 500 mg x 3, Week 2-12: 500 mg x 6</description>
          </group>
          <group group_id="O2">
            <title>Sugar Pills</title>
            <description>Glucose with lemon acid&#xD;
Acetyl-L-carnitine: Week 1: 500 mg x 3, Week 2-12: 500 mg x 6</description>
          </group>
        </group_list>
        <measure>
          <title>Days With Migraine and Side Effects</title>
          <description>Secondary measures will be: Days with migraine; days with headache; hours with headache; headache intensity (0-3 scale) on days with headache; doses of analgesics; doses of triptans; days with sick leave; number of responders (≥ 50% decrease in migraine days compared with baseline); incidence of side effects recorded openly.</description>
          <population>Headache hours per 4 weeks</population>
          <units>Headache hours per 4 weeks</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="72"/>
                <count group_id="O2" value="72"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.4" spread="30.2"/>
                    <measurement group_id="O2" value="37.0" spread="38.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Acetyl-L-carnitine</title>
          <description>Acetyl-L-carnitine tablets&#xD;
Acetyl-L-carnitine: Week 1: 500 mg x 3, Week 2-12: 500 mg x 6</description>
        </group>
        <group group_id="E2">
          <title>Sugar Pills</title>
          <description>Glucose with lemon acid&#xD;
Sugar tablets (500 mg dextrose and citric acid): Week 1: 1 tablet x 3 (1,5 g), week 2-12: 6 tablets (3.0 g):</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="72"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="72"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="72"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>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="25" subjects_at_risk="72"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="72"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>advedrse events</sub_title>
                <description>Pain and/or flatulence</description>
                <counts group_id="E1" events="12" subjects_affected="12" subjects_at_risk="72"/>
                <counts group_id="E2" events="19" subjects_affected="19" subjects_at_risk="72"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>More severe headache</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="72"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="72"/>
              </event>
              <event>
                <sub_title>Bad taste</sub_title>
                <description>Bad taste of tablets</description>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="72"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="72"/>
              </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>Dr. knut Hagen</name_or_title>
      <organization>St. olavs Hospital</organization>
      <phone>95401579</phone>
      <email>knut.hagen@stolav.no</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/NCT01695317
org study id: 2012-001624-36
nct id: NCT01695317
lead sponsor: 
has dmc: Yes
Traditionally, beta blockers have been used for migraine prophylaxis, but in later years also
      antiepileptic drugs. Contraindications and side effects have to some degree limited their
      use, and new prophylactics that can be used by most migraine sufferers and with little side
      effects are in demand. One product that may seem to fulfill these requirements is
      Acetyl-L-carnitine, which is a dietary supplement and naturally occurs in plants and animals.
      L-carnitine is necessary for fatty-acid metabolism and energy production.

      To our knowledge, no placebo-controlled studies have previously evaluated the efficacy of
      Acetyl-L-carnitine in adults with migraine.

      The aims of the present study is to evaluate the efficacy of Acetyl-L-carnitine as a
      prophylaxis in migraine patients
The study will be a single-centre double-blinded, randomized, placebo controlled crossover
      study with Acetyl-L-carnitine or placebo. We plan to include 72 patients. The follow up
      duration will be 36 weeks. The study will be performed according to Good Clinical Practice,
      and relying partly on the International Headache Society Guidelines for controlled trials of
      drugs in migraine from 2012 and partly on the guidelines divulged by the International
      Headache Society task force on trial guidelines for chronic migraine.

      After a screening visit including a neurological consultation, eligible patients will sign an
      informed consent declaration before they enter a 4 week run-in (baseline) period when they
      keep a headache diary. After 4 weeks they return for the second visit. If they have had 2 or
      more migraine attacks they are allowed to proceed in the study. If they have less than 2
      migraine attacks (required for proceeding in the study), they are allowed to extend the
      baseline period another 4 weeks. Those who then during the whole 8 week period have on
      average 2 or more migraine attacks per month are also allowed to proceed. Otherwise they are
      excluded from the study.

      Details of the treatment period The duration of each of the two treatment periods is 12
      weeks. During each period there will be one telephone contact at the start of each treatment
      period to remind patients to start with medicines, and one after 2 weeks to check compliance
      and side effects. In the second last week of every treatment period there will be a doctor
      and nurse visit with drug accounting and dispensing of new medicines for the next period. At
      this visit one will ensure that the patient has just enough medicines left to finish the
      period before the wash-out. As recommended in crossover studies, the participants enter a
      washout period of 4 weeks between the two treatment periods, to reduce the risk of carryover
      effect.

      Randomization Randomization will be generated using a computerized procedure. A randomization
      list containing 72 patient numbers is made before the start of the study, and the patient
      number is then indicated on a package with medicines for that patient. The study has a
      crossover design, and the two different treatment periods (active or placebo) can arise to
      two different treatment sequences (AP or PA). Patients are therefore randomized in blocks of
      4 where one of these two treatment sequences is assigned to each patient in random order.
      With 72 patients to be included, this means that 18 patients are randomized in each block. In
      each block, 50% patients have the treatment sequence AP, and 50% PA in a random order.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Headache Days
time frame: last 4 weeks
description: The number of days per 4 weeks with moderate or severe headache lasting ≥ 4 hours or if treated with the patient's usual headache medication (usually a triptan) as the primary endpoint.
measure: Days With Migraine and Side Effects
time frame: Last 4 weeks
description: Secondary measures will be: Days with migraine; days with headache; hours with headache; headache intensity (0-3 scale) on days with headache; doses of analgesics; doses of triptans; days with sick leave; number of responders (≥ 50% decrease in migraine days compared with baseline); incidence of side effects recorded openly.
arm group label: Acetyl-L-carnitine
arm group type: Active Comparator
description: Acetyl-L-carnitine tablets
arm group label: Sugar pills
arm group type: Placebo Comparator
description: Glucose with lemon acid
intervention type: Drug
intervention name: Acetyl-L-carnitine
description: Week 1: 500 mg x 3, Week 2-12: 500 mg x 6
arm group label: Acetyl-L-carnitine
arm group label: Sugar pills
other name: ALCAR
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Knut Hagen, MD, PhD
role: Principal Investigator
affiliation: Norwegian National Headache Centre
facility: 
country: Norway
citation: Hagen K, Brenner E, Linde M, Gravdahl GB, Tronvik EA, Engstrom M, Sonnewald U, Helde G, Stovner LJ, Sand T. Acetyl-l-carnitine versus placebo for migraine prophylaxis: A randomized, triple-blind, crossover study. Cephalalgia. 2015 Oct;35(11):987-95. doi: 10.1177/0333102414566817. Epub 2015 Jan 19.
PMID: 25601916
responsible party type: Sponsor
mesh term: Migraine Disorders
mesh term: Acetylcarnitine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 