<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/NCT03272503</url>
  </required_header>
  <id_info>
    <org_study_id>Pimozide2_ALS-002</org_study_id>
    <nct_id>NCT03272503</nct_id>
  </id_info>
  <brief_title>A Clinical Trial of Pimozide in Patients With Amyotrophic Lateral Sclerosis (ALS)</brief_title>
  <acronym>Pimozide2</acronym>
  <official_title>A Phase II Randomized, Placebo-Controlled, Double Blinded, Multi-Centre Clinical Trial of Pimozide in Patients With Amyotrophic Lateral Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Calgary</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>ALS Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Brain Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Calgary</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will look at whether Pimozide may help to slow the progression of Amyotrophic&#xD;
      Lateral Sclerosis.&#xD;
&#xD;
      100 people from several Canadian centres with ALS who have provided their consent will be&#xD;
      randomly assigned into one of 2 groups. The first group will receive a dose of up to 2mg of&#xD;
      Pimozide per day and the second group will receive placebo (lactose tablets). Subjects will&#xD;
      be assigned randomly (like by a flip of a coin) to receive either Pimozide 2 mg per day or&#xD;
      placebo tablets. There will be a fifty-fifty chance of receiving Pimozide or placebo.&#xD;
&#xD;
      Participants will be on study medication up to 22 weeks, and on study up to 26 weeks. There&#xD;
      are 8 clinic visits and 1 phone visit over the course of the Treatment Phase of the study.&#xD;
      The second phase which is Observational, is optional with follow-up for up to 5 years from&#xD;
      the end of the Treatment Phase.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease is a neuromuscular disease that&#xD;
      results in rapid decline in normal muscle function and tone leading to difficulties with&#xD;
      mobility, eating, drinking, breathing, sleeping, and communicating. The disease is&#xD;
      progressive and no cure currently exists. Most people diagnosed with ALS succumb within 3 to&#xD;
      5 years. Rilutek® (riluzole) has been approved as a treatment to slow progression of ALS, but&#xD;
      is minimally effective with mean increase in survival of only a few months. Radicava® or&#xD;
      Radicut® (edaravone) has recently been approved in Canada, USA, Japan and South Korea.&#xD;
&#xD;
      Muscular dysfunction present in people with ALS is caused by nerve breakdown and a&#xD;
      dysfunction in the communication between the muscles and the nerves. The area where these&#xD;
      communications occur is called the neuromuscular junction. Some recent studies have focused&#xD;
      on using different medications to enhance communication at the neuromuscular junction with&#xD;
      the goal of improving muscle function as a result. This approach is unproven but may help to&#xD;
      slow the progression of the disease.&#xD;
&#xD;
      Pimozide is a medication that has been demonstrated to enhance communication at the&#xD;
      neuromuscular junction in fish and mice. This study will look at whether Pimozide may help to&#xD;
      slow the progression of ALS.&#xD;
&#xD;
      There are two parts to this study.&#xD;
&#xD;
      Treatment Phase: In the first part of this study, 100 people from several Canadian centres&#xD;
      with ALS who have provided their consent will be randomly assigned into one of 2 groups. The&#xD;
      first group will receive a dose of up to 2mg of Pimozide per day and the second group will&#xD;
      receive placebo (lactose tablets). Subjects will be assigned randomly (like by a flip of a&#xD;
      coin) to receive either Pimozide 2 mg per day or placebo tablets. There will be a fifty-fifty&#xD;
      chance of receiving Pimozide or placebo.&#xD;
&#xD;
      Each Pimozide tablet contains 2 mg of Pimozide. The matching placebo tablets for this study&#xD;
      will look exactly like the Pimozide tablets. Placebos are used in clinical trials to find out&#xD;
      if the results observed in the study are due the drug being tested, or for other reasons.&#xD;
&#xD;
      Neither the subject nor their doctor will know which group a patient belongs to. However, if&#xD;
      an emergency should arise, information about a treatment group will be shared with their&#xD;
      doctor to ensure appropriate medical care. Participants will take their treatment once a day,&#xD;
      every day for about 22 weeks. The total time in the study from the screen visit up until the&#xD;
      last phone call communication is about 26 weeks.&#xD;
&#xD;
      Observational Phase: The second part of this study is optional. It is each subject's decision&#xD;
      whether to participate only in the first part of this study, or in both parts of the study,&#xD;
      or not at all. In the second part of this study, the Canadian Neuromuscular Disease Registry&#xD;
      (CNDR) will collect data on overall ALS progression using the Revised ALS Functional Rating&#xD;
      Scale (ALSFRS-R) and breathing using Vital Capacity data collected during breathing tests.&#xD;
      This information will be collected from a subject medical record following each routine&#xD;
      clinical appointment. Data will be collected at each routine clinic visit for up to 5 years&#xD;
      from the end of the first part of the study. There will be no extra visits for this part of&#xD;
      the study beyond routine ALS clinic visits.&#xD;
&#xD;
      The information collected during this part of the study will be used to compare the&#xD;
      progression of ALS, after the clinical trial is completed, among the two treatment types&#xD;
      (Placebo or 2 mg per day). By analyzing this information, the researchers conducting this&#xD;
      study hope to determine if Pimozide may help to slow the progression of ALS. To participate&#xD;
      in this part of the study consent must be provided to join the CNDR. A subject who hasn't&#xD;
      already provided their CNDR consent, and wishes to participate in this part of the study will&#xD;
      be given a CNDR consent form to review and sign in addition to this consent form. A subject&#xD;
      already participating in the CNDR will just need to sign the main study consent form.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 27, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in ALS Functional Rating Scale-Revised (ALSFRS-R)</measure>
    <time_frame>Change from Baseline (week 2), at visit each of visit weeks 4, 8,12,16,20, week 24 Final Study visit, and week 26 follow-up phone call. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit.</time_frame>
    <description>The Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) consists of a 12 item questionnaire which asks about function in certain daily activities. Takes around 5-10 mins with a study staff member.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Slow Vital Capacity (SVC)</measure>
    <time_frame>Change from screen, at each of visit weeks 8, week 16, and week 24 Final Study visit. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit.</time_frame>
    <description>The SVC is the maximum volume of air which can be exhaled after a deep breath in, during a slow/steady maneuver. A nose clip will be placed on the nose during the testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Decremental responses on repetitive nerve stimulation (DRRNS)</measure>
    <time_frame>Change from Baseline (week 2) at week 24 Final Study visit. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit.</time_frame>
    <description>Repetitive Nerve Stimulation is where electrical stimulation is applied to a motor nerve repeatedly several times per second. This will involve testing each thumb.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Motor Power - the MRC (Medical Research Council) Sum Score</measure>
    <time_frame>Change from screen, at each of week 8, week 16, and week 24 Final Study visit. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit.</time_frame>
    <description>Assessment of Muscle Strength</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Common Terminology Criteria for Adverse Events (CTCAE) will be entered for each visit for adverse effect profile analysis</measure>
    <time_frame>Change from Baseline (week 2), at each of weeks 4,8,12,16,20, week 24 Final Study visit, and week 26 follow-up phone call. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit.</time_frame>
    <description>Adverse events will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in ALS-Specific QOL -Revised</measure>
    <time_frame>Change from Baseline (week 2), at week 24 Final Study visit. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit.</time_frame>
    <description>The Amyotrophic Lateral Sclerosis Specific Quality of Life - Revised (ALSSQOL-R) questionnaire consists of 50 items regarding quality of life. Takes approximately 15 minutes to complete</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Cramp Frequency and Severity</measure>
    <time_frame>Change from Baseline (week 2), at each of weeks 4,8,12,16,20, and week 24 Final Study visit. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit</time_frame>
    <description>Consists of 2 questions asking if subject has had cramps in the last 24 hours, how bad and how severe they were. Takes 1 or 2 minutes to complete.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>ALS</condition>
  <condition>Amyotrophic Lateral Sclerosis</condition>
  <arm_group>
    <arm_group_label>Group 1 Pimozide 2 mg (current) or 4 mg/day (study initiation)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pimozide will be initiated at 2 mg once daily. The maximum dose will then be administered for a target period of 22 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2 Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo tablets will be utilized and administered in an identical manner for subjects in Group 1</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pimozide 2mg/day (current) or 4 mg/day (study initiation)</intervention_name>
    <description>Pimozide 2mg tablets will be taken once daily.</description>
    <arm_group_label>Group 1 Pimozide 2 mg (current) or 4 mg/day (study initiation)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>Identical matching placebo lactose tablets</description>
    <arm_group_label>Group 2 Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients classified as having clinically definite, clinically probable, clinically&#xD;
             probable (laboratory-supported) or clinically possible ALS according to the&#xD;
             El-Escorial diagnostic criteria for ALS (see Appendix 2).&#xD;
&#xD;
          2. Able to comprehend and willing to sign Informed Consent Form (ICF).&#xD;
&#xD;
          3. Age 18 years of age or greater.&#xD;
&#xD;
          4. ALS Symptom onset of muscle weakness or speech impairment no more than 48 months prior&#xD;
             to screen visit. Fasiculations should not be considered.&#xD;
&#xD;
          5. Slow Vital Capacity (SVC) greater than or equal to 50% predicted for sex, age and&#xD;
             height at screen.&#xD;
&#xD;
          6. Has the ability to swallow tablets/capsules whole at study entry.&#xD;
&#xD;
          7. Subject with clinical laboratory findings within the normal range or, if outside the&#xD;
             normal range, determined by the Investigator at the Screening visit to be not&#xD;
             clinically significant.&#xD;
&#xD;
          8. If the subject is taking Riluzole the dose must be stable for 30 days prior to the&#xD;
             randomization visit. Riluzole cannot be initiated during the study.&#xD;
&#xD;
          9. If the subject is receiving Edaravone therapy, the dose must be stable for at least 1&#xD;
             cycle of infusion treatments before the randomization visit.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of laryngeal spasm, dystonia, or akathisia.&#xD;
&#xD;
          2. Diagnosis of ongoing symptomatic Restless Leg Syndrome or undergoing current treatment&#xD;
             for Restless Leg Syndrome. If subject has symptoms that resemble or have the potential&#xD;
             to be Restless Leg Syndrome, then further investigation should be undertaken to&#xD;
             confirm or rule out diagnosis of Restless Leg Syndrome.&#xD;
&#xD;
          3. Any history of moderate or severe traumatic brain injury as defined by a Glasgow Coma&#xD;
             Scale Score of less than 13/15 at any time point following a head injury without&#xD;
             sedation or other reason for a decreased level of consciousness.&#xD;
&#xD;
          4. History of neuroleptic malignant syndrome.&#xD;
&#xD;
          5. History of hypersensitivity or serious adverse reaction(s) to a neuroleptic&#xD;
             medication.&#xD;
&#xD;
          6. History of hyponatremia &lt; 130 mmol/L&#xD;
&#xD;
          7. Subject with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value&#xD;
             &gt;3.0 times the upper limit of normal at the Screening visit.&#xD;
&#xD;
          8. Current heparin or warfarin use.&#xD;
&#xD;
          9. History of hepatic and/or renal impairment that may affect pimozide metabolism&#xD;
&#xD;
         10. History of current pregnancy, or breastfeeding women, or women planning to become&#xD;
             pregnant. Female subjects of childbearing potential (sexually mature female who has&#xD;
             not undergone a hysterectomy or who has not been post-menopausal for 12 consecutive&#xD;
             months), must practise effective contraception during the study and be willing and&#xD;
             able to continue contraception until the Follow-up phone visit after discontinuing&#xD;
             study medication. Abstinence can be considered an acceptable method of contraception&#xD;
             at the discretion of the investigator.&#xD;
&#xD;
         11. Current antipsychotic use&#xD;
&#xD;
         12. Presence of central nervous system depression, comatose states, liver disorders, renal&#xD;
             insufficiency, and blood dyscrasias&#xD;
&#xD;
         13. Presence of Parkinson's syndrome&#xD;
&#xD;
         14. Presence of major depressive disorders as determined by site Investigator.&#xD;
&#xD;
         15. History of clinically significant ECG abnormalities at screen visit, including&#xD;
             QTc&gt;500ms.&#xD;
&#xD;
         16. History of congenital long QT syndrome or with a family history of this syndrome and&#xD;
             in patients with a history of cardiac arrhythmias or Torsade de Pointes.&#xD;
&#xD;
         17. Presence of acquired long QT interval, and/or concomitant use of drugs known to&#xD;
             prolong the QT interval (TCAs, opioids such as methodone, quinolone antibiotics&#xD;
             (ciprofloxacin), antimalarials (quinine), Detrol, azole antifungals, Class 1A, III and&#xD;
             1C antiarrhythmics, and macrolide antibiotics.&#xD;
&#xD;
         18. Presence of clinically significant bradycardia (heart rate &lt; 50 beats per minute)&#xD;
&#xD;
         19. Presence of hypokalemia or hypomagnesemia.&#xD;
&#xD;
         20. The concomitant use of CYP 3A4-inhibiting drugs such as azole antimycotics, antiviral&#xD;
             protease inhibitors, macrolide antibiotics and nefazodone.&#xD;
&#xD;
         21. The concomitant use of CYP 2D6-inhibiting drugs such as quinidine is also&#xD;
             contraindicated.&#xD;
&#xD;
         22. Concomitant use of serotonin reuptake inhibitors, such as, sertraline, paroxetine,&#xD;
             citalopram and escitalopram.*&#xD;
&#xD;
         23. Has taken any compound under current or known future study as a potential therapy&#xD;
             (including Withania) for ALS less than 30 days prior to dosing OR history of exposure&#xD;
             to stem cell therapy for treatment of ALS at any time.&#xD;
&#xD;
         24. Current Neurological impairment due to a condition other than ALS:&#xD;
&#xD;
               1. Subject in whom causes of neuromuscular weakness other than ALS have not been&#xD;
                  excluded.&#xD;
&#xD;
               2. Subject with a diagnosis of other neurodegenerative diseases (e.g., Parkinson's&#xD;
                  disease, Frontotemporal dementia, Alzheimer's disease, etc.)&#xD;
&#xD;
         25. Use of non-invasive ventilation (BiPAP or CPAP) prior to Baseline visit at any time.&#xD;
&#xD;
         26. Cognitive impairment as determined by the Site Investigator, subject must not have an&#xD;
             impaired ability to provide informed consent and must be able to understand study&#xD;
             processes and comply with study procedures.&#xD;
&#xD;
         27. Extrapyramidal Symptom Rating Scale (ESRS) Parkinsonism score of 2 on 2 items or a&#xD;
             score &gt; 3 on 1 item; OR Dystonia score of &gt;3 on at least 1 item or a score of 2 on 2&#xD;
             items; OR Tardive Dyskinesia score of &gt;3 on at least 1 item or a score of 2 on 2&#xD;
             items. Do not consider scores greater than 3 for Tremor in any region if due to Benign&#xD;
             Essential, Exaggerated, or Physiological Tremor.&#xD;
&#xD;
         28. The concomitant use of SSRIs and tricyclic antidepressants (e.g. amitriptyline,&#xD;
             amoxaprine, desipramine, doxepin, imipramine, nortriptyline, protripyline,&#xD;
             trimipramine) - and Tolterodine (Detrol) CYP2D6 inhibitor.&#xD;
&#xD;
               -  Prohibited medications such as tricyclic antidepressants, antimalarials, and&#xD;
                  serotonin reuptake inhibitors,(ie sertraline, paroxetine, citalopram, fluoxetine,&#xD;
                  vilazodone and escitalopram) may be weaned to full discontinuation at the&#xD;
                  screening visit after consent has been signed (no study procedures including&#xD;
                  adjustments to medication may occur until informed consent has been provided).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lawrence Korngut, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Calgary and Alberta Health Services</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Pim2 Study</last_name>
    <phone>403-210-7006</phone>
    <email>Pimozide2@ucalgary.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Janet Petrillo, M.Sc.</last_name>
    <phone>403-210-7006</phone>
    <email>japetril@ucalgary.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Dr. Lawrence Korngut -South Health Campus</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T3M 1M4</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Janet Petrillo, MSc</last_name>
      <phone>403-210-7006</phone>
      <email>japetril@ucalgary.ca</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Dr. Wendy Johnston - University of Alberta</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G2G3</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kelsey Tymkow</last_name>
      <phone>780-492-7690</phone>
      <email>tymkow@ualberta.ca</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Dr. Colleen O'Connell - Stan Cassidy Centre for Rehabilitation</name>
      <address>
        <city>Fredericton</city>
        <state>New Brunswick</state>
        <zip>E3B 0C7</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Susan McCully, MN</last_name>
      <phone>506-447-4095</phone>
      <email>susan.mccully@horizonnb.ca</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Dr. John Turnbull McMaster University/Hamilton Health Services</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8N 3Z5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Daniela Trapsa</last_name>
      <phone>905-521-2100</phone>
      <phone_ext>76365</phone_ext>
      <email>trapsd@mcmaster.ca</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Dr. Christen Shoesmith - London Health Sciences Centre</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A5A5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christine Piechowicz, BA</last_name>
      <phone>519-685-8500</phone>
      <phone_ext>34858</phone_ext>
      <email>christine.piechowicz@lhsc.on.ca</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Dr. Ariel Breiner -Ottawa Hospital Research Institute</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1Y4E9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sergio Guber, MSc</last_name>
      <phone>613-798-5555</phone>
      <phone_ext>19627</phone_ext>
      <email>sguber@ohri.ca</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Dr. Lorne Zinman Sunnybrook Research Institute</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N 3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Liane Phung, BSc</last_name>
      <phone>416-480-6100</phone>
      <phone_ext>87561</phone_ext>
      <email>liane.phung@sri.utoronto.ca</email>
    </contact>
    <contact_backup>
      <last_name>Shirley Pham, BA</last_name>
      <phone>416-480-6860</phone>
      <email>shirley.pham@sunnybrook.ca</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Dr. Sandrine Larue - Reserche Sepmus Inc.</name>
      <address>
        <city>Greenfield Park</city>
        <state>Quebec</state>
        <zip>J4V 2J2</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kim Desilets, B.Sc.</last_name>
      <phone>450-672-1931</phone>
      <phone_ext>247</phone_ext>
      <email>larue@neurorivesud.ca</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Dr. Genevieve Matte</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H2L4M1</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Micheline Gravel</last_name>
      <phone>514-890-8000</phone>
      <phone_ext>13616</phone_ext>
      <email>micheline.gravel.chum@ssss.gouv.qc.ca</email>
    </contact>
    <contact_backup>
      <last_name>Stefanie Houle</last_name>
      <phone>514-890-8000</phone>
      <phone_ext>27208</phone_ext>
      <email>stefanie.houle.chum@ssss.gouv.qc.ca</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>August 31, 2017</study_first_submitted>
  <study_first_submitted_qc>September 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <last_update_submitted>May 26, 2020</last_update_submitted>
  <last_update_submitted_qc>May 26, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 28, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Calgary</investigator_affiliation>
    <investigator_full_name>DR. LAWRENCE KORNGUT</investigator_full_name>
    <investigator_title>M.D. Director Calgary ALS and Motor Neuron Disease Clinic</investigator_title>
  </responsible_party>
  <keyword>Pimozide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Motor Neuron Disease</mesh_term>
    <mesh_term>Amyotrophic Lateral Sclerosis</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pimozide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03272503
org study id: Pimozide2_ALS-002
nct id: NCT03272503
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study will look at whether Pimozide may help to slow the progression of Amyotrophic
      Lateral Sclerosis.

      100 people from several Canadian centres with ALS who have provided their consent will be
      randomly assigned into one of 2 groups. The first group will receive a dose of up to 2mg of
      Pimozide per day and the second group will receive placebo (lactose tablets). Subjects will
      be assigned randomly (like by a flip of a coin) to receive either Pimozide 2 mg per day or
      placebo tablets. There will be a fifty-fifty chance of receiving Pimozide or placebo.

      Participants will be on study medication up to 22 weeks, and on study up to 26 weeks. There
      are 8 clinic visits and 1 phone visit over the course of the Treatment Phase of the study.
      The second phase which is Observational, is optional with follow-up for up to 5 years from
      the end of the Treatment Phase.
Amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease is a neuromuscular disease that
      results in rapid decline in normal muscle function and tone leading to difficulties with
      mobility, eating, drinking, breathing, sleeping, and communicating. The disease is
      progressive and no cure currently exists. Most people diagnosed with ALS succumb within 3 to
      5 years. Rilutek® (riluzole) has been approved as a treatment to slow progression of ALS, but
      is minimally effective with mean increase in survival of only a few months. Radicava® or
      Radicut® (edaravone) has recently been approved in Canada, USA, Japan and South Korea.

      Muscular dysfunction present in people with ALS is caused by nerve breakdown and a
      dysfunction in the communication between the muscles and the nerves. The area where these
      communications occur is called the neuromuscular junction. Some recent studies have focused
      on using different medications to enhance communication at the neuromuscular junction with
      the goal of improving muscle function as a result. This approach is unproven but may help to
      slow the progression of the disease.

      Pimozide is a medication that has been demonstrated to enhance communication at the
      neuromuscular junction in fish and mice. This study will look at whether Pimozide may help to
      slow the progression of ALS.

      There are two parts to this study.

      Treatment Phase: In the first part of this study, 100 people from several Canadian centres
      with ALS who have provided their consent will be randomly assigned into one of 2 groups. The
      first group will receive a dose of up to 2mg of Pimozide per day and the second group will
      receive placebo (lactose tablets). Subjects will be assigned randomly (like by a flip of a
      coin) to receive either Pimozide 2 mg per day or placebo tablets. There will be a fifty-fifty
      chance of receiving Pimozide or placebo.

      Each Pimozide tablet contains 2 mg of Pimozide. The matching placebo tablets for this study
      will look exactly like the Pimozide tablets. Placebos are used in clinical trials to find out
      if the results observed in the study are due the drug being tested, or for other reasons.

      Neither the subject nor their doctor will know which group a patient belongs to. However, if
      an emergency should arise, information about a treatment group will be shared with their
      doctor to ensure appropriate medical care. Participants will take their treatment once a day,
      every day for about 22 weeks. The total time in the study from the screen visit up until the
      last phone call communication is about 26 weeks.

      Observational Phase: The second part of this study is optional. It is each subject's decision
      whether to participate only in the first part of this study, or in both parts of the study,
      or not at all. In the second part of this study, the Canadian Neuromuscular Disease Registry
      (CNDR) will collect data on overall ALS progression using the Revised ALS Functional Rating
      Scale (ALSFRS-R) and breathing using Vital Capacity data collected during breathing tests.
      This information will be collected from a subject medical record following each routine
      clinical appointment. Data will be collected at each routine clinic visit for up to 5 years
      from the end of the first part of the study. There will be no extra visits for this part of
      the study beyond routine ALS clinic visits.

      The information collected during this part of the study will be used to compare the
      progression of ALS, after the clinical trial is completed, among the two treatment types
      (Placebo or 2 mg per day). By analyzing this information, the researchers conducting this
      study hope to determine if Pimozide may help to slow the progression of ALS. To participate
      in this part of the study consent must be provided to join the CNDR. A subject who hasn't
      already provided their CNDR consent, and wishes to participate in this part of the study will
      be given a CNDR consent form to review and sign in addition to this consent form. A subject
      already participating in the CNDR will just need to sign the main study consent form.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in ALS Functional Rating Scale-Revised (ALSFRS-R)
time frame: Change from Baseline (week 2), at visit each of visit weeks 4, 8,12,16,20, week 24 Final Study visit, and week 26 follow-up phone call. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit.
description: The Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) consists of a 12 item questionnaire which asks about function in certain daily activities. Takes around 5-10 mins with a study staff member.
measure: Change in Slow Vital Capacity (SVC)
time frame: Change from screen, at each of visit weeks 8, week 16, and week 24 Final Study visit. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit.
description: The SVC is the maximum volume of air which can be exhaled after a deep breath in, during a slow/steady maneuver. A nose clip will be placed on the nose during the testing.
measure: Change in Decremental responses on repetitive nerve stimulation (DRRNS)
time frame: Change from Baseline (week 2) at week 24 Final Study visit. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit.
description: Repetitive Nerve Stimulation is where electrical stimulation is applied to a motor nerve repeatedly several times per second. This will involve testing each thumb.
measure: Change in Motor Power - the MRC (Medical Research Council) Sum Score
time frame: Change from screen, at each of week 8, week 16, and week 24 Final Study visit. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit.
description: Assessment of Muscle Strength
measure: Change in Common Terminology Criteria for Adverse Events (CTCAE) will be entered for each visit for adverse effect profile analysis
time frame: Change from Baseline (week 2), at each of weeks 4,8,12,16,20, week 24 Final Study visit, and week 26 follow-up phone call. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit.
description: Adverse events will be assessed.
measure: Change in ALS-Specific QOL -Revised
time frame: Change from Baseline (week 2), at week 24 Final Study visit. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit.
description: The Amyotrophic Lateral Sclerosis Specific Quality of Life - Revised (ALSSQOL-R) questionnaire consists of 50 items regarding quality of life. Takes approximately 15 minutes to complete
measure: Change in Cramp Frequency and Severity
time frame: Change from Baseline (week 2), at each of weeks 4,8,12,16,20, and week 24 Final Study visit. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit
description: Consists of 2 questions asking if subject has had cramps in the last 24 hours, how bad and how severe they were. Takes 1 or 2 minutes to complete.
arm group label: Group 1 Pimozide 2 mg (current) or 4 mg/day (study initiation)
arm group type: Experimental
description: Pimozide will be initiated at 2 mg once daily. The maximum dose will then be administered for a target period of 22 weeks.
arm group label: Group 2 Placebo
arm group type: Placebo Comparator
description: Placebo tablets will be utilized and administered in an identical manner for subjects in Group 1
intervention type: Drug
intervention name: Pimozide 2mg/day (current) or 4 mg/day (study initiation)
description: Pimozide 2mg tablets will be taken once daily.
arm group label: Group 1 Pimozide 2 mg (current) or 4 mg/day (study initiation)
intervention type: Drug
intervention name: Placebo Oral Tablet
description: Identical matching placebo lactose tablets
arm group label: Group 2 Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lawrence Korngut, M.D.
role: Principal Investigator
affiliation: University of Calgary and Alberta Health Services
last name: Pim2 Study
phone: 403-210-7006
email: Pimozide2@ucalgary.ca
last name: Janet Petrillo, M.Sc.
phone: 403-210-7006
email: japetril@ucalgary.ca
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: University of Calgary
investigator full name: DR. LAWRENCE KORNGUT
investigator title: M.D. Director Calgary ALS and Motor Neuron Disease Clinic
mesh term: Motor Neuron Disease
mesh term: Amyotrophic Lateral Sclerosis
mesh term: Sclerosis
mesh term: Pimozide
sharing ipd: No