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/NCT05974293</url>
    </required_header>
    <id_info>
      <org_study_id>sens_nmo_001</org_study_id>
      <nct_id>NCT05974293</nct_id>
    </id_info>
    <brief_title>A Phase IIb Study of Nabiximols for Spasticity Due to Neuromyelitis Optica Spectrum Disorders</brief_title>
    <acronym>SENS-NMO</acronym>
    <official_title>A Phase IIb Study of the Safety and Efficacy of Nabiximols in Subjects With Spasticity Due to Neuromyelitis Optica Spectrum Disorders: A Double-blind, Randomized, Placebo-Controlled, Crossover Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Michael, Levy M.D.,Ph.D.</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Jazz Pharmaceuticals</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Massachusetts General Hospital</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this clinical trial is to evaluate the safety and efficacy of nabiximols, a&#xD;
        cannabinoid spray, for the treatment of moderate to severe spasticity in adult patients with&#xD;
        AQP4-IgG positive and antibody-negative NMOSD. The main question it aims to answer is whether&#xD;
        treatment with nabiximols improves patient-reported spasticity ratings compared to treatment&#xD;
        with a placebo. This trial will also answer whether nabiximols impact pain, spasm frequency,&#xD;
        mood, walking ability, and sleep. Participants will be mailed the treatments and placebo&#xD;
        treatments, and will be asked to complete study visits and questionnaires remotely. There is&#xD;
        also an optional sub-study that involves in-person visits with ultrasound imaging and&#xD;
        in-person neurologic exams.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Patients with NMOSD often have medication-resistant and severe spasticity due to&#xD;
        longitudinally extensive spinal cord lesions. Existing treatments are limited by their&#xD;
        efficacy and tolerability. Cannabinoids have been shown to quantitatively improve spasticity&#xD;
        in mouse models of neuroinflammation, and nabiximols, a cannabinoid-based oromucosal spray,&#xD;
        have demonstrated efficacy for medication-resistant spasticity in multiple sclerosis.&#xD;
        However, no studies have as yet explored the use of nabiximols specifically in NMOSD, and&#xD;
        there is a significant unmet need for new symptomatic treatments in this patient population.&#xD;
        The goal of this study is to evaluate the safety and efficacy of nabiximols spray, for the&#xD;
        treatment of moderate to severe spasticity in adult patients with AQP4-IgG positive and&#xD;
        seronegative NMOSD. This study is designed as a phase IIb, single-site, double-blind,&#xD;
        randomized, placebo-controlled 2x2 crossover clinical trial, with a 2-week washout period&#xD;
        between treatment periods. After randomization, each participant enters into Period 1, which&#xD;
        begins with a 2-week dose escalation period with a pre-defined dose escalation scheme,&#xD;
        followed by a 4-week stable treatment period. After completion of Period 1, all participants&#xD;
        have a 2-week washout period and then enter Period 2, where they again complete a 2-week dose&#xD;
        escalation period and 4-week constant treatment period. The patient-reported 0-10 numeric&#xD;
        rating scale for spasticity (NRS-S) is the primary outcome measure. All key study procedures&#xD;
        are performed virtually, including a weekly electronic study diary, additional weekly&#xD;
        surveys, and 8 virtual video-based study visits including a screening visit and safety follow&#xD;
        up visit. Additional optional in-person assessments of spasticity (neurologic exam, modified&#xD;
        Ashworth Scale and muscle ultrasound elastography) will be performed for a selection of local&#xD;
        participants. In total, the study has a 20-week duration per participant, from the screening&#xD;
        visit to the final study completion for safety follow-up visit, including 12 weeks of&#xD;
        on-treatment time.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">April 2024</start_date>
    <completion_date type="Anticipated">September 2026</completion_date>
    <primary_completion_date type="Anticipated">April 2026</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Crossover Assignment</intervention_model>
      <intervention_model_description>This is a phase II, single-site, double-blind, randomized, placebo-controlled 2 by 2 crossover clinical trial designed to evaluate the efficacy of nabiximols compared to placebo for the treatment of NMOSD-related spasticity.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change in mean Numeric Rating Scale - Spasticity (NRS-S) scores from pre-treatment to post-treatment</measure>
      <time_frame>Baseline; Up to week 18</time_frame>
      <description>Numeric Rating Scale - Spasticity (NRS-S) score is a 0-10 point, patient-reported scale indicating spasticity severity.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Proportion of participants with NRS-S response corresponding to a minimal clinically important difference (MCID) (&gt;18% difference) from pre-treatment to post-treatment</measure>
      <time_frame>Baseline; Up to week 18</time_frame>
      <description>Numeric Rating Scale - Spasticity (NRS-S) score is a 0-10 point, patient-reported, single item scale indicating spasticity severity.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of participants with NRS-S response corresponding to a clinically important difference (CID) (&gt;30% difference) from pre-treatment to post-treatment</measure>
      <time_frame>Baseline; Up to week 18</time_frame>
      <description>Numeric Rating Scale - Spasticity (NRS-S) score is a 0-10 point, patient-reported scale indicating spasticity severity.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Penn Spasm Frequency Scale (PSFS) score from pre-treatment to post-treatment</measure>
      <time_frame>Baseline; Up to week 18</time_frame>
      <description>The Penn Spasm Frequency Scale (PSFS) is a 2-item patient-reported scale indicating spasm frequency and severity</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in mean PROMIS NRS v1.0 - Pain Intensity 3a scores from pre-treatment to post-treatment</measure>
      <time_frame>Baseline; Up to week 18</time_frame>
      <description>The PROMIS NRS v1.0 - Pain Intensity 3a form is a 3-item patient-reported scale indicating worst pain, average pain, and current pain in the prior week</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in mean PROMIS SF v1.1 - Pain Interference 8a scores from pre-treatment to post-treatment</measure>
      <time_frame>Baseline; Up to week 18</time_frame>
      <description>The PROMIS SF v1.1-Pain Interference 8a form is an 8-item scale indicating the degree to which pain interferes with functioning</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in mean Multiple Sclerosis Spasticity Scale - 88 (MSSS-88) sub-scale 2 (pain and discomfort) scores from pre-treatment to post-treatment</measure>
      <time_frame>Baseline; Up to week 18</time_frame>
      <description>The Multiple Sclerosis Spasticity Scale - 88 (MSSS-88) form sub-scale 2 (pain and discomfort) is a 9-item patient-reported scale indicating the impact of spasticity on pain and discomfort</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Floodlight-5 U-Turn Test (5-UTT) from pre-treatment to post-treatment</measure>
      <time_frame>Baseline; Up to week 18</time_frame>
      <description>The Floodlight-5 U-Turn Test (5-UTT) is a smartphone application-based test that evaluates ambulation, and specifically turn speed in seconds</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Floodlight-2 Minute Walk Test (2MWT) from pre-treatment to post-treatment</measure>
      <time_frame>Baseline; Up to week 18</time_frame>
      <description>The Floodlight-2 Minute Walk Test (2MWT) is is a smartphone application-based test that evaluates ambulation speed in seconds</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in mean Multiple Sclerosis Spasticity Scale - 88 (MSSS-88) sub-scale 5 (walking) scores from pre-treatment to post-treatment</measure>
      <time_frame>Baseline; Up to week 18</time_frame>
      <description>The Multiple Sclerosis Spasticity Scale - 88 (MSSS-88) form sub-scale 2 (pain and discomfort) is a 10-item patient-reported scale indicating the impact of spasticity on walking</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in PROMIS SF v1.0 - Sleep Disturbance 4A from pre-treatment to post-treatment</measure>
      <time_frame>Baseline; Up to week 18</time_frame>
      <description>The PROMIS SF v1.0 - Sleep Disruption 4A is a 4-item patient-reported scale indicating sleep quality</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Numeric Rating Scale-Sleep Disruption (NRS-SD) from pre-treatment to post-treatment</measure>
      <time_frame>Baseline; Up to week 18</time_frame>
      <description>The Numeric Rating Scale-Sleep Disruption (NRS-SD) is a single-item 0-10 scale where participants can indicate the degree to which spasticity impacts sleep</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of participants reporting 'very much improved,' 'much improved,' and 'slightly improved' symptoms in the Global Impression of Change (GIC) by subject (SGIC) scores from pre-treatment to post-treatment</measure>
      <time_frame>Baseline; Up to week 18</time_frame>
      <description>The Global Impression of Change (GIC) by subject (SGIC) is a 7-point, single-item scale indicating the direction and degree of change that participants experience</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Visual Analogue Scale - Quality of Life (VAS-QL) from pre-treatment to post-treatment</measure>
      <time_frame>Baseline; Up to week 18</time_frame>
      <description>The Visual Analogue Scale - Quality of Life (VAS-QL) is a 100mm visual analog scale ranging from 0 (very low) to 100 (very high) on which respondents record their perception of quality of life</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of participants who are tolerant of treatment</measure>
      <time_frame>Screening; Up to week 18</time_frame>
      <description>Tolerance is defined as not discontinuing study drug and at least 50% compliance</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of participants who are tolerant of treatment</measure>
      <time_frame>Screening; Up to week 20</time_frame>
      <description>Tolerance is defined as not discontinuing study drug and at least 50% compliance</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with treatment-emergent adverse events while on each treatment</measure>
      <time_frame>Screening; Up to week 20</time_frame>
      <description>Treatment-emergent adverse events will be tabulated for each arm during each study period and compared between treatment and placebo</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Screening and at each subsequent time-point with reference to the last assessment</measure>
      <time_frame>Screening; Up to week 20</time_frame>
      <description>The Columbia-Suicide Severity Rating Scale is assessment tool that evaluates suicidal ideation and behavior</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Change in mean Patient Health Questionnaire-8 (PHQ-8) scores from pre-treatment to post-treatment</measure>
      <time_frame>Screening; Up to week 20</time_frame>
      <description>The Patient Health Questionnaire-8 is an 8-item self-administered depression scale</description>
    </other_outcome>
    <other_outcome>
      <measure>Change in mean PROMIS SF v1.0 - Anxiety 4a scores from pre-treatment to post-treatment</measure>
      <time_frame>Screening; Up to week 20</time_frame>
      <description>The PROMIS SF v1.0 - Anxiety 4a scale is a 4-item self-administered anxiety questionnaire</description>
    </other_outcome>
    <other_outcome>
      <measure>Change in mean Floodlight-Pinching Test (PT) scores from pre-treatment to post-treatment</measure>
      <time_frame>Screening; Up to week 18</time_frame>
      <description>The Floodlight-Pinching Test (PT) is a smartphone application-based test assessing hand and arm function</description>
    </other_outcome>
    <other_outcome>
      <measure>Change in mean Floodlight-Draw a Shape Test (DaS) scores from pre-treatment to post-treatment</measure>
      <time_frame>Screening; Up to week 18</time_frame>
      <description>The Floodlight-Draw a Shape Test (DaS) is a smartphone application-based test assessing hand and arm function</description>
    </other_outcome>
    <other_outcome>
      <measure>Change in mean Floodlight-e-Symbol Digit Modalities Test (eSDMT) scores from pre-treatment to post-treatment</measure>
      <time_frame>Screening; Up to week 18</time_frame>
      <description>The Floodlight-Draw a Shape Test (DaS) is a smartphone application-based test assessing cognition</description>
    </other_outcome>
    <other_outcome>
      <measure>Change in Lower Limb Muscle Tone-6 (LLMT-6) scores as measured by the modified Ashworth Scale scores from pre-treatment to post-treatment</measure>
      <time_frame>Screening; Up to week 18</time_frame>
      <description>LLMT-6 is defined as the average of the 6 individual Modified Ashworth Scale (MAS) transformed scores of knee flexors, knee extensors, and plantar flexors on both sides of the body</description>
    </other_outcome>
    <other_outcome>
      <measure>Change in muscle shear wave speed from pre-treatment to post-treatment</measure>
      <time_frame>Screening; Up to week 18</time_frame>
      <description>Muscle shear wave speed is measured using shear wave elastography, an ultrasound-based technique to assess muscle stiffness</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">44</enrollment>
    <condition>NMO Spectrum Disorder</condition>
    <condition>Spasticity, Muscle</condition>
    <arm_group>
      <arm_group_label>Nabiximols, then Placebo</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>During Period 1, participants receive daily nabiximols spray, delivered by a pump action oromucosal spray. The first 2 weeks of Period 1 are the titration period with participants following pre-specified uptitration schedule, until they reach their individualized optimum daily dosage, with a maximum of 12 daily sprays. Following these 2 weeks, they continue the optimum dose for 4 weeks. Then, they undergo a 2-week washout period, and then, enter Period 2 where they receive the matched placebo spray and again undergo a 2-week titration period, and a 4-week consistent daily dosage period.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo, then Nabiximols</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>During Period 1, participants receive daily matched placebo spray, delivered by a pump action oromucosal spray. The first 2 weeks of Period 1 are the titration period with participants following pre-specified uptitration schedule, until they reach their individualized optimum daily dosage, with a maximum of 12 daily sprays. Following these 2 weeks, they continue the optimum dose for 4 weeks. Then, they undergo a 2-week washout period, and then, enter Period 2 where they receive the active nabiximols spray and again undergo a 2-week titration period, and a 4-week consistent daily dosage period.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Nabiximols</intervention_name>
      <description>Nabiximols is is a yellow-brown oromucosal spray solution containing 27 mg/mL of THC and 25 mg/mL of CBD.</description>
      <arm_group_label>Nabiximols, then Placebo</arm_group_label>
      <arm_group_label>Placebo, then Nabiximols</arm_group_label>
      <other_name>Sativex</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>The placebo is a matching oromucosal spray that is identical to the investigational study product in terms of packaging, labelling, schedule of administration, dosing instructions, and appearance.</description>
      <arm_group_label>Nabiximols, then Placebo</arm_group_label>
      <arm_group_label>Placebo, then Nabiximols</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Confirmed diagnosis of NMOSD, meeting the International Panel for NMO Diagnosis (IPND)&#xD;
               NMOSD criteria (Appendix 1), including NMOSD with AQP4-IgG, and NMOSD without AQP4-IgG&#xD;
  &#xD;
            -  Aged between 18 years or older, at the time of signing the informed consent&#xD;
  &#xD;
            -  Willing and able to give informed consent and to participate in all study procedures&#xD;
  &#xD;
            -  Moderate to severe spasticity, as defined by a score of &gt; 3 on the 0-10 numerical&#xD;
               rating scale for spasticity (NRS-S) at the time of screening&#xD;
  &#xD;
            -  Reports NMOSD-related spasticity symptoms ongoing for at least 6 months&#xD;
  &#xD;
            -  Spasticity is determined to be causally related to an NMOSD attack in the opinion of&#xD;
               the investigator&#xD;
  &#xD;
            -  No relapses, and otherwise stable disease (i.e. no significant recovery from relapse&#xD;
               or other change in disability) for at least 6 months, in the opinion of the&#xD;
               investigator&#xD;
  &#xD;
            -  Anti-spasticity regimen, if on medications, maintained at a stable dose for the 30&#xD;
               days prior to enrollment without adequate relief of spasticity symptoms.&#xD;
  &#xD;
            -  Willing to maintain a stable dose of non-study-related anti-spasticity medication for&#xD;
               the duration of the study, barring significant changes to their medical condition.&#xD;
  &#xD;
            -  Willing to allow his or her primary care doctor and primary neurologist, if&#xD;
               appropriate, to be notified of participation in the study.&#xD;
  &#xD;
            -  Documentation of negative MOG-IgG, if diagnosis is NMOSD without AQP4-IgG positive&#xD;
               status. Participant with presumptive diagnosis of NMOSD without AQP4-IgG and no prior&#xD;
               MOG IgG testing can have MOG testing sent, and be eligible for participation if this&#xD;
               is negative.&#xD;
  &#xD;
            -  For women of childbearing potential: participants who are not lactating, not pregnant,&#xD;
               and not planning to become pregnant in the next 8 months and who agree to remain&#xD;
               abstinent (refrain from heterosexual intercourse) or use adequate contraception during&#xD;
               the treatment period and for at least 3 months after the final dose of nabiximols.&#xD;
  &#xD;
            -  For males with partners who are females of childbearing potential: participants who&#xD;
               agree to remain abstinent (refrain from heterosexual intercourse) or use adequate&#xD;
               contraception during the treatment period and for at least 3 months after the final&#xD;
               dose of nabiximols.&#xD;
  &#xD;
            -  Able to use the necessary electronic applications (either via smartphone, tablet, or&#xD;
               desktop) and has an email address.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Consumption of cannabis herb or other cannabinoid-based drugs within 30 days prior to&#xD;
               study entry.&#xD;
  &#xD;
            -  Unwillingness to abstain from consumption of cannabis herb or other cannabinoid-based&#xD;
               drugs for the duration of the study.&#xD;
  &#xD;
            -  Known or suspected hypersensitivity or adverse reaction (including psychiatric adverse&#xD;
               reactions) to cannabinoids or cannabinoid products, ethanol, peppermint oil or&#xD;
               propylene glycol.&#xD;
  &#xD;
            -  Currently receiving a prohibited medication and unwilling or unable to stop for the&#xD;
               duration of the study. Prohibited medications include: CYP3A4 inhibitors:&#xD;
               clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir,&#xD;
               verapamil, etc.; CYP3A4 inducers: rifampicin, phenobarbital, phenytoin, St. John's&#xD;
               Wort. Of note, the CYP3A4 inducer carbamazepine is permitted, but a stable dosage must&#xD;
               be maintained throughout the study (no as needed dosing permitted). Other prohibited&#xD;
               medications: regular levodopa (Sinemet, Sinemet Plus, Levodopa, L-dopa, Madopar,&#xD;
               Benserazide), sildenafil (Viagra), fentanyl, or antiarrhythmic medications.&#xD;
  &#xD;
            -  Receipt of an investigational medicinal product or participation in a therapeutic&#xD;
               clinical trial within 30 days prior to the initial visit&#xD;
  &#xD;
            -  Received a Botulinum Toxin injection within four months prior to the screening visit&#xD;
               or unwillingness to stop receiving Botulinum Toxin injections for the relief of&#xD;
               spasticity for the duration of the study.&#xD;
  &#xD;
            -  Personal medical history of schizophrenia, severe personality disorders, other major&#xD;
               psychotic disorders, or other major psychiatric disorders other than depression and&#xD;
               anxiety.&#xD;
  &#xD;
            -  Family history in 1st degree relatives of schizophrenia or other psychotic disorders.&#xD;
  &#xD;
            -  Hospitalization for depression or anxiety within the 2 years prior to the screening&#xD;
               visit.&#xD;
  &#xD;
            -  A documented history of attempted suicide or suicidal ideation of category 4 or 5&#xD;
               according to the Columbia Suicide Severity Rating Scale (C-SSRS) screening, OR if in&#xD;
               the Investigator's judgment, the participant is at risk for a suicide attempt.&#xD;
  &#xD;
            -  Known or suspected history of a substance use disorder or heavy alcohol consumption&#xD;
               excluding tobacco use disorder or cannabis use not meeting criteria for cannabis use&#xD;
               disorder.&#xD;
  &#xD;
            -  History of myocardial infarction or clinically significant ischemic heart disease,&#xD;
               arrhythmias (other than well controlled atrial fibrillation), poorly controlled&#xD;
               hypertension or severe heart failure. .&#xD;
  &#xD;
            -  Significant renal or hepatic impairment, either in the opinion of the investigator, or&#xD;
               by the following laboratory screening values: AST or ALT &gt; 2 × upper limit of normal&#xD;
               (ULN); Total bilirubin &gt; 2 × ULN (unless due to Gilbert's syndrome); BUN &gt; 2 × upper&#xD;
               limit of normal (ULN)&#xD;
  &#xD;
            -  History of epilepsy or recurrent seizures.&#xD;
  &#xD;
            -  Concomitant disease or disorder that has symptoms of spasticity, and that in the&#xD;
               opinion of the Investigator may influence the study outcome and endpoint assessment.&#xD;
  &#xD;
            -  Any other significant medical or psychiatric condition which, in the opinion of the&#xD;
               investigator, may either put the participant at risk because of participation in the&#xD;
               study, or may influence the result of the study or the participant's ability to&#xD;
               participate in the study.&#xD;
  &#xD;
            -  Scheduled elective surgery or other procedures which require general anesthesia during&#xD;
               the study period.&#xD;
  &#xD;
            -  Intention to donate blood during the study.&#xD;
  &#xD;
            -  Intention to travel internationally during the study.&#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>Michael Levy, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Massachusetts General Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Anastasia Vishnevetsky, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Massachusetts General Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Anastasia Vishnevetsky, MD</last_name>
      <phone>2034309425</phone>
      <email>avishnevetsky@partners.org</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Rebecca Salky</last_name>
      <email>rsalky@mgh.harvard.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Massachusetts General Hospital</name>
        <address>
          <city>Boston</city>
          <state>Massachusetts</state>
          <zip>02114</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Anastasia Vishnevetsky, MD</last_name>
        <email>avishnevetsky@partners.org</email>
      </contact>
      <contact_backup>
        <last_name>Rebecca Salky</last_name>
        <email>rsalky@mgh.harvard.edu</email>
      </contact_backup>
      <investigator>
        <last_name>Michael Levy, MD, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Anastasia Vishnevetsky, MD, MPH</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Sarah Eby, MD, MPH</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Phillipe-Antoine Bilodeau, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 26, 2023</study_first_submitted>
    <study_first_submitted_qc>August 2, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 3, 2023</study_first_posted>
    <last_update_submitted>August 2, 2023</last_update_submitted>
    <last_update_submitted_qc>August 2, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 3, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
      <investigator_full_name>Michael, Levy M.D.,Ph.D.</investigator_full_name>
      <investigator_title>Associate Professor of Neurology at Massachusetts General Hospital</investigator_title>
    </responsible_party>
    <keyword>Neuromyelitis Optica Spectrum Disorders</keyword>
    <keyword>Nabiximols</keyword>
    <keyword>Cannabinoid</keyword>
    <keyword>Sativex</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Muscle Spasticity</mesh_term>
      <mesh_term>Neuromyelitis Optica</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Nabiximols</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>No specific plan to share individual participant data with other researchers.</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/NCT05974293
  org study id: sens_nmo_001
  nct id: NCT05974293
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  The goal of this clinical trial is to evaluate the safety and efficacy of nabiximols, a
        cannabinoid spray, for the treatment of moderate to severe spasticity in adult patients with
        AQP4-IgG positive and antibody-negative NMOSD. The main question it aims to answer is whether
        treatment with nabiximols improves patient-reported spasticity ratings compared to treatment
        with a placebo. This trial will also answer whether nabiximols impact pain, spasm frequency,
        mood, walking ability, and sleep. Participants will be mailed the treatments and placebo
        treatments, and will be asked to complete study visits and questionnaires remotely. There is
        also an optional sub-study that involves in-person visits with ultrasound imaging and
        in-person neurologic exams.
  Patients with NMOSD often have medication-resistant and severe spasticity due to
        longitudinally extensive spinal cord lesions. Existing treatments are limited by their
        efficacy and tolerability. Cannabinoids have been shown to quantitatively improve spasticity
        in mouse models of neuroinflammation, and nabiximols, a cannabinoid-based oromucosal spray,
        have demonstrated efficacy for medication-resistant spasticity in multiple sclerosis.
        However, no studies have as yet explored the use of nabiximols specifically in NMOSD, and
        there is a significant unmet need for new symptomatic treatments in this patient population.
        The goal of this study is to evaluate the safety and efficacy of nabiximols spray, for the
        treatment of moderate to severe spasticity in adult patients with AQP4-IgG positive and
        seronegative NMOSD. This study is designed as a phase IIb, single-site, double-blind,
        randomized, placebo-controlled 2x2 crossover clinical trial, with a 2-week washout period
        between treatment periods. After randomization, each participant enters into Period 1, which
        begins with a 2-week dose escalation period with a pre-defined dose escalation scheme,
        followed by a 4-week stable treatment period. After completion of Period 1, all participants
        have a 2-week washout period and then enter Period 2, where they again complete a 2-week dose
        escalation period and 4-week constant treatment period. The patient-reported 0-10 numeric
        rating scale for spasticity (NRS-S) is the primary outcome measure. All key study procedures
        are performed virtually, including a weekly electronic study diary, additional weekly
        surveys, and 8 virtual video-based study visits including a screening visit and safety follow
        up visit. Additional optional in-person assessments of spasticity (neurologic exam, modified
        Ashworth Scale and muscle ultrasound elastography) will be performed for a selection of local
        participants. In total, the study has a 20-week duration per participant, from the screening
        visit to the final study completion for safety follow-up visit, including 12 weeks of
        on-treatment time.
  allocation: Randomized
  intervention model: Crossover Assignment
  intervention model description: This is a phase II, single-site, double-blind, randomized, placebo-controlled 2 by 2 crossover clinical trial designed to evaluate the efficacy of nabiximols compared to placebo for the treatment of NMOSD-related spasticity.
  primary purpose: Treatment
  masking: Triple (Participant, Investigator, Outcomes Assessor)
  measure: Change in mean Numeric Rating Scale - Spasticity (NRS-S) scores from pre-treatment to post-treatment
  time frame: Baseline; Up to week 18
  description: Numeric Rating Scale - Spasticity (NRS-S) score is a 0-10 point, patient-reported scale indicating spasticity severity.
  measure: Proportion of participants with NRS-S response corresponding to a minimal clinically important difference (MCID) (>18% difference) from pre-treatment to post-treatment
  time frame: Baseline; Up to week 18
  description: Numeric Rating Scale - Spasticity (NRS-S) score is a 0-10 point, patient-reported, single item scale indicating spasticity severity.
  measure: Proportion of participants with NRS-S response corresponding to a clinically important difference (CID) (>30% difference) from pre-treatment to post-treatment
  time frame: Baseline; Up to week 18
  description: Numeric Rating Scale - Spasticity (NRS-S) score is a 0-10 point, patient-reported scale indicating spasticity severity.
  measure: Change in Penn Spasm Frequency Scale (PSFS) score from pre-treatment to post-treatment
  time frame: Baseline; Up to week 18
  description: The Penn Spasm Frequency Scale (PSFS) is a 2-item patient-reported scale indicating spasm frequency and severity
  measure: Change in mean PROMIS NRS v1.0 - Pain Intensity 3a scores from pre-treatment to post-treatment
  time frame: Baseline; Up to week 18
  description: The PROMIS NRS v1.0 - Pain Intensity 3a form is a 3-item patient-reported scale indicating worst pain, average pain, and current pain in the prior week
  measure: Change in mean PROMIS SF v1.1 - Pain Interference 8a scores from pre-treatment to post-treatment
  time frame: Baseline; Up to week 18
  description: The PROMIS SF v1.1-Pain Interference 8a form is an 8-item scale indicating the degree to which pain interferes with functioning
  measure: Change in mean Multiple Sclerosis Spasticity Scale - 88 (MSSS-88) sub-scale 2 (pain and discomfort) scores from pre-treatment to post-treatment
  time frame: Baseline; Up to week 18
  description: The Multiple Sclerosis Spasticity Scale - 88 (MSSS-88) form sub-scale 2 (pain and discomfort) is a 9-item patient-reported scale indicating the impact of spasticity on pain and discomfort
  measure: Change in Floodlight-5 U-Turn Test (5-UTT) from pre-treatment to post-treatment
  time frame: Baseline; Up to week 18
  description: The Floodlight-5 U-Turn Test (5-UTT) is a smartphone application-based test that evaluates ambulation, and specifically turn speed in seconds
  measure: Change in Floodlight-2 Minute Walk Test (2MWT) from pre-treatment to post-treatment
  time frame: Baseline; Up to week 18
  description: The Floodlight-2 Minute Walk Test (2MWT) is is a smartphone application-based test that evaluates ambulation speed in seconds
  measure: Change in mean Multiple Sclerosis Spasticity Scale - 88 (MSSS-88) sub-scale 5 (walking) scores from pre-treatment to post-treatment
  time frame: Baseline; Up to week 18
  description: The Multiple Sclerosis Spasticity Scale - 88 (MSSS-88) form sub-scale 2 (pain and discomfort) is a 10-item patient-reported scale indicating the impact of spasticity on walking
  measure: Change in PROMIS SF v1.0 - Sleep Disturbance 4A from pre-treatment to post-treatment
  time frame: Baseline; Up to week 18
  description: The PROMIS SF v1.0 - Sleep Disruption 4A is a 4-item patient-reported scale indicating sleep quality
  measure: Change in Numeric Rating Scale-Sleep Disruption (NRS-SD) from pre-treatment to post-treatment
  time frame: Baseline; Up to week 18
  description: The Numeric Rating Scale-Sleep Disruption (NRS-SD) is a single-item 0-10 scale where participants can indicate the degree to which spasticity impacts sleep
  measure: Proportion of participants reporting 'very much improved,' 'much improved,' and 'slightly improved' symptoms in the Global Impression of Change (GIC) by subject (SGIC) scores from pre-treatment to post-treatment
  time frame: Baseline; Up to week 18
  description: The Global Impression of Change (GIC) by subject (SGIC) is a 7-point, single-item scale indicating the direction and degree of change that participants experience
  measure: Change in Visual Analogue Scale - Quality of Life (VAS-QL) from pre-treatment to post-treatment
  time frame: Baseline; Up to week 18
  description: The Visual Analogue Scale - Quality of Life (VAS-QL) is a 100mm visual analog scale ranging from 0 (very low) to 100 (very high) on which respondents record their perception of quality of life
  measure: Proportion of participants who are tolerant of treatment
  time frame: Screening; Up to week 18
  description: Tolerance is defined as not discontinuing study drug and at least 50% compliance
  measure: Proportion of participants who are tolerant of treatment
  time frame: Screening; Up to week 20
  description: Tolerance is defined as not discontinuing study drug and at least 50% compliance
  measure: Number of participants with treatment-emergent adverse events while on each treatment
  time frame: Screening; Up to week 20
  description: Treatment-emergent adverse events will be tabulated for each arm during each study period and compared between treatment and placebo
  measure: Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Screening and at each subsequent time-point with reference to the last assessment
  time frame: Screening; Up to week 20
  description: The Columbia-Suicide Severity Rating Scale is assessment tool that evaluates suicidal ideation and behavior
  measure: Change in mean Patient Health Questionnaire-8 (PHQ-8) scores from pre-treatment to post-treatment
  time frame: Screening; Up to week 20
  description: The Patient Health Questionnaire-8 is an 8-item self-administered depression scale
  measure: Change in mean PROMIS SF v1.0 - Anxiety 4a scores from pre-treatment to post-treatment
  time frame: Screening; Up to week 20
  description: The PROMIS SF v1.0 - Anxiety 4a scale is a 4-item self-administered anxiety questionnaire
  measure: Change in mean Floodlight-Pinching Test (PT) scores from pre-treatment to post-treatment
  time frame: Screening; Up to week 18
  description: The Floodlight-Pinching Test (PT) is a smartphone application-based test assessing hand and arm function
  measure: Change in mean Floodlight-Draw a Shape Test (DaS) scores from pre-treatment to post-treatment
  time frame: Screening; Up to week 18
  description: The Floodlight-Draw a Shape Test (DaS) is a smartphone application-based test assessing hand and arm function
  measure: Change in mean Floodlight-e-Symbol Digit Modalities Test (eSDMT) scores from pre-treatment to post-treatment
  time frame: Screening; Up to week 18
  description: The Floodlight-Draw a Shape Test (DaS) is a smartphone application-based test assessing cognition
  measure: Change in Lower Limb Muscle Tone-6 (LLMT-6) scores as measured by the modified Ashworth Scale scores from pre-treatment to post-treatment
  time frame: Screening; Up to week 18
  description: LLMT-6 is defined as the average of the 6 individual Modified Ashworth Scale (MAS) transformed scores of knee flexors, knee extensors, and plantar flexors on both sides of the body
  measure: Change in muscle shear wave speed from pre-treatment to post-treatment
  time frame: Screening; Up to week 18
  description: Muscle shear wave speed is measured using shear wave elastography, an ultrasound-based technique to assess muscle stiffness
  arm group label: Nabiximols, then Placebo
  arm group type: Experimental
  description: During Period 1, participants receive daily nabiximols spray, delivered by a pump action oromucosal spray. The first 2 weeks of Period 1 are the titration period with participants following pre-specified uptitration schedule, until they reach their individualized optimum daily dosage, with a maximum of 12 daily sprays. Following these 2 weeks, they continue the optimum dose for 4 weeks. Then, they undergo a 2-week washout period, and then, enter Period 2 where they receive the matched placebo spray and again undergo a 2-week titration period, and a 4-week consistent daily dosage period.
  arm group label: Placebo, then Nabiximols
  arm group type: Experimental
  description: During Period 1, participants receive daily matched placebo spray, delivered by a pump action oromucosal spray. The first 2 weeks of Period 1 are the titration period with participants following pre-specified uptitration schedule, until they reach their individualized optimum daily dosage, with a maximum of 12 daily sprays. Following these 2 weeks, they continue the optimum dose for 4 weeks. Then, they undergo a 2-week washout period, and then, enter Period 2 where they receive the active nabiximols spray and again undergo a 2-week titration period, and a 4-week consistent daily dosage period.
  intervention type: Drug
  intervention name: Nabiximols
  description: Nabiximols is is a yellow-brown oromucosal spray solution containing 27 mg/mL of THC and 25 mg/mL of CBD.
  arm group label: Nabiximols, then Placebo
  arm group label: Placebo, then Nabiximols
  other name: Sativex
  intervention type: Drug
  intervention name: Placebo
  description: The placebo is a matching oromucosal spray that is identical to the investigational study product in terms of packaging, labelling, schedule of administration, dosing instructions, and appearance.
  arm group label: Nabiximols, then Placebo
  arm group label: Placebo, then Nabiximols
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Michael Levy, MD, PhD
  role: Principal Investigator
  affiliation: Massachusetts General Hospital
  last name: Anastasia Vishnevetsky, MD, PhD
  role: Principal Investigator
  affiliation: Massachusetts General Hospital
  last name: Anastasia Vishnevetsky, MD
  phone: 2034309425
  email: avishnevetsky@partners.org
  last name: Rebecca Salky
  email: rsalky@mgh.harvard.edu
  facility: 
  contact: 
  contact backup: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  country: United States
  responsible party type: Sponsor-Investigator
  investigator affiliation: Massachusetts General Hospital
  investigator full name: Michael, Levy M.D.,Ph.D.
  investigator title: Associate Professor of Neurology at Massachusetts General Hospital
  mesh term: Muscle Spasticity
  mesh term: Neuromyelitis Optica
  mesh term: Nabiximols
  sharing ipd: No
  ipd description: No specific plan to share individual participant data with other researchers.