xml: <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/NCT06008249</url>
    </required_header>
    <id_info>
      <org_study_id>MAGNET</org_study_id>
      <nct_id>NCT06008249</nct_id>
    </id_info>
    <brief_title>Platform Trial to Assess the Efficacy of Multiple Drugs in Amyotrophic Lateral Sclerosis (ALS)</brief_title>
    <official_title>A Multi-arm, Adaptive, Group-sequential Trial NETwork to Evaluate Drug Efficacy in Patients With Amyotrophic Lateral Sclerosis (ALS)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Stichting TRICALS Foundation</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Stichting ALS Nederland</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Fight MND</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Research Foundation Flanders</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>MNDA</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Thierry Latran Foundation</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Ulla-Carin Lindquist Foundation</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Luzon Foundation</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Alan Davidson Foundation</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>My name'5 Doddie Foundation</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Stichting TRICALS Foundation</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>
        The objective of this phase III, placebo-controlled platform study is to investigate the&#xD;
        efficacy of drugs for patients with ALS (Amyotrophic lateral sclerosis).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study uses an innovative multi-arm, adaptive trial design to investigate the efficacy of&#xD;
        multiple treatments simultaneously. Currently one study-arm is active, investigating the&#xD;
        efficacy and safety of lithium carbonate versus placebo in patients with ALS. Only patients&#xD;
        with a specific UNC13A genotype (approximately 1 in 6 ALS patients) are eligible to&#xD;
        participate.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 9, 2021</start_date>
    <completion_date type="Anticipated">June 2026</completion_date>
    <primary_completion_date type="Anticipated">June 2026</primary_completion_date>
    <phase>Phase 3</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>
      <intervention_model_description>Participants will be randomised in a 2:1 ratio to receive either lithium carbonate or placebo</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
      <masking_description>Double-blind</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Overall survival, defined as time to death from any cause or respiratory insufficiency (DRI; defined as tracheostomy or the use of non-invasive ventilation for ≥22 h per day for ≥10 consecutive days)</measure>
      <time_frame>endpoint or 24 months</time_frame>
      <description>A tracheostomy for ventilation is meant here</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Composite endpoint evaluating daily functioning and survival based on the joint model framework of survival and longitudinal ALSFRS-R total scores</measure>
      <time_frame>endpoint or 24 months</time_frame>
      <description>The ALSFRS-R (Amyotrophic Lateral Sclerosis Rating Scale-revised) is a 12 item participant self-report measure that monitors ALS disease progression, where a higher score reflects a better outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Daily functioning, defined as mean change from baseline in ALSFRS-R total score.</measure>
      <time_frame>endpoint or 24 months</time_frame>
      <description>The ALSFRS-R (Amyotrophic Lateral Sclerosis Rating Scale-revised) is a 12 item participant self-report measure that monitors ALS disease progression, where a higher score reflects a better outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Respiratory function, defined as mean change from baseline in SVC (%predicted of normal according to the GLI-2012 reference standard)</measure>
      <time_frame>endpoint or 24 months</time_frame>
      <description>Slow vital capacity (SVC) is measured in litres, and as a % of predicted. A higher score reflects a better outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Quality of life, defined as change from baseline on the EQ-5D Visual Analogue Scale (single-item scale)</measure>
      <time_frame>endpoint or 24 months</time_frame>
      <description>The EQ-5D-5L (EuroQol 5 Dimension 5 Level) questionnaire is a standardised measure of health-related Quality of Life, using a Visual Analogue Scale. A higher score relates to a better outcome</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Quality of life, defined as change from baseline on the EQ-5D</measure>
      <time_frame>endpoint or 24 months</time_frame>
      <description>The EQ-5D-5L (EuroQol 5 Dimension 5 Level) questionnaire is a standardised measure of health-related Quality of Life. A lower score relates to a better outcome</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Neuropsychological status, defined as change from baseline on the ECAS</measure>
      <time_frame>endpoint or 24 months</time_frame>
      <description>ECAS (Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis Screen) is a multidomain assessment questionnaire used in ALS to assess cognitive and behavioural changes where a higher score relates to a better outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Neuropsychological status, defined as change from baseline on the ALS-FTD-Q.</measure>
      <time_frame>endpoint or 24 months</time_frame>
      <description>ALS-FTD-Q (Amyotrophic Lateral Sclerosis-Frontotemporal Dementia-Questionnaire) is a validated instrument for the screening of behavioral disturbances in ALS.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clinical disease stage, defined as mean time spent in each stage of the King's and ALS Milano-Torino staging systems.</measure>
      <time_frame>endpoint or 24 months</time_frame>
      <description>The King's Staging Scale is a clinical staging system defining four stages of ALS assessed by way of a semi-structured interview with the participant.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in laboratory parameters: Urinary P75ECD (ectodomain of neurotrophin receptor p75), Neurofilament light and heavy chain, Plasma creatinine</measure>
      <time_frame>endpoint or 24 months</time_frame>
      <description>Plasma creatinine is assessed to monitor kidney function</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Tolerability defined as time-to-discontinuation of assigned treatment since randomization</measure>
      <time_frame>endpoint or 24 months</time_frame>
      <description>the number of participants who discontinue study medication will be assessed to assess tolerability</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety based on the safety assessments including neurological examinations, clinical laboratory evaluations, vital signs and frequency of adverse events (AEs) or serious adverse events (SAEs).</measure>
      <time_frame>endpoint or 24 months</time_frame>
      <description>(S)AEs will be categorized according to the Common Terminology Criteria for Adverse Events and will be rated for severity and association with study drug.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">171</enrollment>
    <condition>Amyotrophic Lateral Sclerosis</condition>
    <arm_group>
      <arm_group_label>Lithium carbonate</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Lithium carbonate 400 mg capsules will be taken once daily, starting with one capsule (400 mg daily) initially titrated up to two or three capsules daily, depending on blood lithium levels. The target range for the lithium plasma level will be between ≥0.4 mmol/l and ≤ 0.8 mmol/l. Maximum duration is 24 months.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Patients start with 1 capsule to be taken once daily, with subsequent sham dose adjustments made to patients on placebo to maintain blinding in clinical sites.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Lithium Carbonate 400 MG</intervention_name>
      <description>Lithium carbonate vs placebo (2:1)</description>
      <arm_group_label>Lithium carbonate</arm_group_label>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. ≥ 18 years at the time of screening.&#xD;
  &#xD;
            2. Diagnosis of ALS according to the revised El Escorial criteria (possible,&#xD;
               probable-laboratory supported, probable or definite).&#xD;
  &#xD;
            3. Capable of providing informed consent and complying with trial procedures, including&#xD;
               randomization to sub-studies.&#xD;
  &#xD;
            4. TRICALS risk profile &gt; -6.0 and &lt; -2.0 **&#xD;
  &#xD;
            5. The use of riluzole will be permitted during the study. Subjects taking riluzole must&#xD;
               be on a stable dose for at least 30 days prior to the baseline visit, or stopped&#xD;
               taking riluzole at least 30 days prior to the baseline visit.&#xD;
  &#xD;
            6. Women of childbearing potential* must have a negative pregnancy test at baseline and&#xD;
               be non-lactating.&#xD;
  &#xD;
            7. Men must agree to practice contraception for the duration of the trial and for at&#xD;
               least 3 months after last dose of study drug.&#xD;
  &#xD;
            8. Men must not plan to father a child or to provide sperm for donation for the duration&#xD;
               of the trial and 3 months after the last dose of study drug.&#xD;
  &#xD;
            9. Women must not be able to become pregnant (e.g. post-menopausal***, surgically sterile&#xD;
               or using effective birth control methods) for the duration of the study. Effective&#xD;
               contraceptives are defined as having a failure rate of less than 1% per year when used&#xD;
               consistently and correctly and, when applicable, in accordance with the product label,&#xD;
               including: abstinence, hormonal contraception, intrauterine device in place for ≥ 3&#xD;
               months Appendix 1). Women of childbearing potential must have a negative pregnancy&#xD;
               test at baseline, and be non-lactating. Women who are pregnant or are actively seeking&#xD;
               to become pregnant, and women of reproductive potential who are not using effective&#xD;
               contraceptives are excluded.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Laboratory Criteria at baseline:&#xD;
  &#xD;
                 -  ALT (alanine transaminase) ≥ 5 times upper limit of normal (ULN)&#xD;
  &#xD;
                 -  AST (aspartate aminotransferase) ≥ 3 times ULN&#xD;
  &#xD;
                 -  Bilirubin ≥ 1.5 times ULN&#xD;
  &#xD;
                 -  Estimated glomerular filtration rate (eGFR) &lt; 50 mL / min / 1.73 m2 based on&#xD;
                    Cystatin C, if not available eGFR can also be calculated based on creatinine&#xD;
                    clearance.&#xD;
  &#xD;
                 -  Platelet concentration of &lt; 100 x109 per L&#xD;
  &#xD;
                 -  Absolute neutrophil count of &lt; 1x109 per L&#xD;
  &#xD;
                 -  Haemoglobin &lt; 100 g/L (&lt;6.2 mmol/L)&#xD;
  &#xD;
                 -  Amylase &amp; lipase ≥ 2 times ULN (suspected pancreatitis)&#xD;
  &#xD;
                 -  Lactate ≥ 2 times ULN (suspected lactate acidosis)&#xD;
  &#xD;
            2. Moderate to severe hepatic impairment according to Child-Pugh classification (Class B&#xD;
               or higher; score ≥ 7). Child-Pugh classification is based on bilirubin, albumin,&#xD;
               International Normalized Ratio (INR) and presence of encephalopathy or ascites.&#xD;
  &#xD;
            3. Participation in any other investigational drug trial or using investigational drug&#xD;
               (within 30 days prior to screening).&#xD;
  &#xD;
            4. Hypothyroidism unresponsive to thyroid hormone supplementation.&#xD;
  &#xD;
            5. Subjects using non-invasive ventilation (NIV, ≥22 h per day) or having a tracheostomy.&#xD;
  &#xD;
            6. Subjects taking edaravone within 30 days prior to screening. Edaravone is approved by&#xD;
               the FDA, but remains an investigational product in Europe and Australia.&#xD;
  &#xD;
            7. Clinically significant history of unstable or severe cardiac (e.g. congestive heart&#xD;
               failure, coronary insufficiency and arrhythmias), oncological, hepatic or renal&#xD;
               disease, neuromuscular diseases, significant pulmonary disorder or other medically&#xD;
               significant illness.&#xD;
  &#xD;
            8. Drug or alcohol abuse.&#xD;
  &#xD;
            9. Unstable psychiatric illness defined as psychosis or untreated major depression within&#xD;
               90 days of the screening visit. This exclusion criterion is based on a prior&#xD;
               psychiatric diagnosis that is unstable as determined by the subject's treating&#xD;
               Psychiatrist.&#xD;
  &#xD;
           10. Presence of frontotemporal dementia which prevents informed consent.&#xD;
  &#xD;
          Lithium carbonate study-specific exclusion criteria:&#xD;
  &#xD;
            1. Patients heterozygous or homozygous for the A-allele of rs12608932 (UNC13A)&#xD;
  &#xD;
            2. Known allergy or hypersensitivity to lithium, or its excipients, or to the components&#xD;
               of the placebo.&#xD;
  &#xD;
            3. Brain injury with posttraumatic epilepsy or neurologic deficit, excluding a concussion&#xD;
               in the medical history. Brain infarction is an exclusion criterion, a transient&#xD;
               ischemic attack is not.&#xD;
  &#xD;
            4. Addison disease.&#xD;
  &#xD;
            5. Patients with the following co-medication: antipsychotics, digoxin and calcium&#xD;
               antagonists, carbamazepine, methyldopa, verapamil and diltiazem.&#xD;
  &#xD;
            6. Brugada Syndrome or family history of Brugada Syndrome.&#xD;
  &#xD;
            7. Plasma sodium &lt;120 mmol/L&#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>Leonard Van den Berg, MD</last_name>
      <role>Study Chair</role>
      <affiliation>TRICALS Foundation</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Roel Vink, PhD</last_name>
      <phone>+31 6 50177777</phone>
      <email>magnet@tricals.org</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Leonard van den Berg, MD</last_name>
      <phone>0887557939</phone>
      <phone_ext>0031</phone_ext>
      <email>L.H.vandenBerg@umcutrecht.nl</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Flinders Medical Centre</name>
        <address>
          <city>Adelaide</city>
          <zip>SA 5042</zip>
          <country>Australia</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Eleanor Ramsey</last_name>
        <email>eleanor.ramsey@sydney.edu.au</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Royal Brisbane and Women's Hospital</name>
        <address>
          <city>Brisbane</city>
          <zip>QLD 4029</zip>
          <country>Australia</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Eleanor Ramsey</last_name>
        <email>eleanor.ramsey@sydney.edu.au</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Calvary Health Care Bethlehem</name>
        <address>
          <city>Parkdale</city>
          <zip>VIC 3195</zip>
          <country>Australia</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Eleanor Ramsey</last_name>
        <email>eleanor.ramsey@sydney.edu.au</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Perron Institute</name>
        <address>
          <city>Perth</city>
          <zip>WA 6009</zip>
          <country>Australia</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Eleanor Ramsey</last_name>
        <email>eleanor.ramsey@sydney.edu.au</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>The University of Sydney (Royal prince Alfred hospital)</name>
        <address>
          <city>Sydney</city>
          <zip>NSW 2050</zip>
          <country>Australia</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Eleanor Ramsey</last_name>
        <email>eleanor.ramsey@sydney.edu.au</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Concord hospital Sydney</name>
        <address>
          <city>Sydney</city>
          <zip>NSW 2139</zip>
          <country>Australia</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Eleanor Ramsey</last_name>
        <email>eleanor.ramsey@sydney.edu.au</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>University Hospital Leuven</name>
        <address>
          <city>Leuven</city>
          <zip>3000</zip>
          <country>Belgium</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Nikita Lamaire</last_name>
        <email>nikita.lamaire@uzleuven.be</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>University Medical Center Utrecht</name>
        <address>
          <city>Utrecht</city>
          <zip>3584 CX</zip>
          <country>Netherlands</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Valerie van Eck</last_name>
        <email>V.D.vanEck@umcutrecht.nl</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Bellvitge University Hospital</name>
        <address>
          <city>Barcelona</city>
          <zip>08907</zip>
          <country>Spain</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Monica Povedano, MD</last_name>
        <email>mpovedano@bellvitgehospital.cat</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Karolinska University Hospital</name>
        <address>
          <city>Stockholm</city>
          <zip>171 64</zip>
          <country>Sweden</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Charlotta Molin Edlund</last_name>
        <email>charlotta.molin-edlund@regionstockholm.se</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>King's College Hospital</name>
        <address>
          <city>London</city>
          <zip>SE5 9RS</zip>
          <country>United Kingdom</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Theresa Chiwera</last_name>
        <email>tchiwera@nhs.net</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>University College London Hospital NHS</name>
        <address>
          <city>London</city>
          <zip>WC1N 3BG</zip>
          <country>United Kingdom</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Andrea Malaspina, MD</last_name>
        <email>a.malaspina@nhs.net</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>University Hospitals of North Midlands NHS Trust</name>
        <address>
          <city>Stoke-on-Trent</city>
          <zip>ST4 6QG</zip>
          <country>United Kingdom</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Thomas Lambert, MD</last_name>
        <email>Thomas.Lambert@uhnm.nhs.uk</email>
      </contact>
    </location>
    <location_countries>
      <country>Australia</country>
      <country>Belgium</country>
      <country>Netherlands</country>
      <country>Spain</country>
      <country>Sweden</country>
      <country>United Kingdom</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 14, 2023</study_first_submitted>
    <study_first_submitted_qc>August 21, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 23, 2023</study_first_posted>
    <last_update_submitted>August 21, 2023</last_update_submitted>
    <last_update_submitted_qc>August 21, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 23, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <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>Lithium Carbonate</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
      <ipd_description>Pending on privacy regulations.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06008249
  org study id: MAGNET
  nct id: NCT06008249
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The objective of this phase III, placebo-controlled platform study is to investigate the
        efficacy of drugs for patients with ALS (Amyotrophic lateral sclerosis).
  This study uses an innovative multi-arm, adaptive trial design to investigate the efficacy of
        multiple treatments simultaneously. Currently one study-arm is active, investigating the
        efficacy and safety of lithium carbonate versus placebo in patients with ALS. Only patients
        with a specific UNC13A genotype (approximately 1 in 6 ALS patients) are eligible to
        participate.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Participants will be randomised in a 2:1 ratio to receive either lithium carbonate or placebo
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  masking description: Double-blind
  measure: Overall survival, defined as time to death from any cause or respiratory insufficiency (DRI; defined as tracheostomy or the use of non-invasive ventilation for ≥22 h per day for ≥10 consecutive days)
  time frame: endpoint or 24 months
  description: A tracheostomy for ventilation is meant here
  measure: Composite endpoint evaluating daily functioning and survival based on the joint model framework of survival and longitudinal ALSFRS-R total scores
  time frame: endpoint or 24 months
  description: The ALSFRS-R (Amyotrophic Lateral Sclerosis Rating Scale-revised) is a 12 item participant self-report measure that monitors ALS disease progression, where a higher score reflects a better outcome.
  measure: Daily functioning, defined as mean change from baseline in ALSFRS-R total score.
  time frame: endpoint or 24 months
  description: The ALSFRS-R (Amyotrophic Lateral Sclerosis Rating Scale-revised) is a 12 item participant self-report measure that monitors ALS disease progression, where a higher score reflects a better outcome.
  measure: Respiratory function, defined as mean change from baseline in SVC (%predicted of normal according to the GLI-2012 reference standard)
  time frame: endpoint or 24 months
  description: Slow vital capacity (SVC) is measured in litres, and as a % of predicted. A higher score reflects a better outcome.
  measure: Quality of life, defined as change from baseline on the EQ-5D Visual Analogue Scale (single-item scale)
  time frame: endpoint or 24 months
  description: The EQ-5D-5L (EuroQol 5 Dimension 5 Level) questionnaire is a standardised measure of health-related Quality of Life, using a Visual Analogue Scale. A higher score relates to a better outcome
  measure: Quality of life, defined as change from baseline on the EQ-5D
  time frame: endpoint or 24 months
  description: The EQ-5D-5L (EuroQol 5 Dimension 5 Level) questionnaire is a standardised measure of health-related Quality of Life. A lower score relates to a better outcome
  measure: Neuropsychological status, defined as change from baseline on the ECAS
  time frame: endpoint or 24 months
  description: ECAS (Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis Screen) is a multidomain assessment questionnaire used in ALS to assess cognitive and behavioural changes where a higher score relates to a better outcome.
  measure: Neuropsychological status, defined as change from baseline on the ALS-FTD-Q.
  time frame: endpoint or 24 months
  description: ALS-FTD-Q (Amyotrophic Lateral Sclerosis-Frontotemporal Dementia-Questionnaire) is a validated instrument for the screening of behavioral disturbances in ALS.
  measure: Clinical disease stage, defined as mean time spent in each stage of the King's and ALS Milano-Torino staging systems.
  time frame: endpoint or 24 months
  description: The King's Staging Scale is a clinical staging system defining four stages of ALS assessed by way of a semi-structured interview with the participant.
  measure: Change from baseline in laboratory parameters: Urinary P75ECD (ectodomain of neurotrophin receptor p75), Neurofilament light and heavy chain, Plasma creatinine
  time frame: endpoint or 24 months
  description: Plasma creatinine is assessed to monitor kidney function
  measure: Tolerability defined as time-to-discontinuation of assigned treatment since randomization
  time frame: endpoint or 24 months
  description: the number of participants who discontinue study medication will be assessed to assess tolerability
  measure: Safety based on the safety assessments including neurological examinations, clinical laboratory evaluations, vital signs and frequency of adverse events (AEs) or serious adverse events (SAEs).
  time frame: endpoint or 24 months
  description: (S)AEs will be categorized according to the Common Terminology Criteria for Adverse Events and will be rated for severity and association with study drug.
  arm group label: Lithium carbonate
  arm group type: Experimental
  description: Lithium carbonate 400 mg capsules will be taken once daily, starting with one capsule (400 mg daily) initially titrated up to two or three capsules daily, depending on blood lithium levels. The target range for the lithium plasma level will be between ≥0.4 mmol/l and ≤ 0.8 mmol/l. Maximum duration is 24 months.
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Patients start with 1 capsule to be taken once daily, with subsequent sham dose adjustments made to patients on placebo to maintain blinding in clinical sites.
  intervention type: Drug
  intervention name: Lithium Carbonate 400 MG
  description: Lithium carbonate vs placebo (2:1)
  arm group label: Lithium carbonate
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Leonard Van den Berg, MD
  role: Study Chair
  affiliation: TRICALS Foundation
  last name: Roel Vink, PhD
  phone: +31 6 50177777
  email: magnet@tricals.org
  last name: Leonard van den Berg, MD
  phone: 0887557939
  phone ext: 0031
  email: L.H.vandenBerg@umcutrecht.nl
  facility: 
  status: Not yet recruiting
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  contact: 
  country: Australia
  country: Belgium
  country: Netherlands
  country: Spain
  country: Sweden
  country: United Kingdom
  responsible party type: Sponsor
  mesh term: Motor Neuron Disease
  mesh term: Amyotrophic Lateral Sclerosis
  mesh term: Sclerosis
  mesh term: Lithium Carbonate
  sharing ipd: Undecided
  ipd description: Pending on privacy regulations.