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/NCT06027567</url>
    </required_header>
    <id_info>
      <org_study_id>IIH:DUAL</org_study_id>
      <nct_id>NCT06027567</nct_id>
    </id_info>
    <brief_title>The Effect of an Anti-obesity Drug, Semaglutide, as Treatment in New-onset Idiopathic Intracranial Hypertension (IIH) Compared to Standard Weight Management (Dietician) With Regards to Change in Weight and Intracranial Pressure</brief_title>
    <acronym>IIH:DUAL</acronym>
    <official_title>Glucagon-like Peptide-1 Receptor (GLP-1R) Analogue Assisted Rapid Weight Loss Program as Treatment of Idiopathic Intracranial Hypertension</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Rigmor Højland Jensen</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Rigshospitalet, Denmark</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Odense University Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>University of Copenhagen</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Danish Headache Center</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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        50 patients with verified new-onset Idiopathic Intracranial Hypertension are randomly&#xD;
        allocated to standard weight management (dietician counselling) or trial intervention&#xD;
        consisting of subcutaneous injections with Semaglutide for 10 months combined, in the initial&#xD;
        8 weeks following diagnosis, with a Very Low Calorie-Diet (max 800 kcal/day)&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Idiopathic Intracranial Hypertension is primarily observed in obese female and weight&#xD;
        management promotes disease control by yet unsettled mechanisms. Effective, fast and lasting&#xD;
        weight loss is crucial, however, hard to achieve. Current weight management strategy in IIH&#xD;
        in Denmark is counselling by a dietician. This study investigates whether an initial Very Low&#xD;
        Calorie Diet (max 800 kcal/day) for 8 weeks following the diagnosis combined with GLP1-RA&#xD;
        treatment throughout 10 months is tolerated and more efficient in achieving substantial&#xD;
        weight loss and reduction of intracranial pressure. Furthermore, a number of secondary&#xD;
        outcomes are measured including headache burden, quality of life, structure and function of&#xD;
        the optic nerve, non-invasive surrogate markers of intracranial pressure, body fat mass, bone&#xD;
        health, fatty liver disease and a range of cerebrospinal-, blood- and urine markers of i.a.&#xD;
        the hormonal, inflammatory, metabolic, and headache biomarker profile.&#xD;
  &#xD;
        The intervention may candidate as a future first-line treatment regime.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">September 2, 2022</start_date>
    <completion_date type="Anticipated">December 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">March 31, 2025</primary_completion_date>
    <phase>Phase 4</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>Open label randomized controlled clinical treatment trial Patients are randomly assigned 1:1 to standard-of-care or intervention</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Weight</measure>
      <time_frame>8 weeks</time_frame>
      <description>Weight change (%)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Intracranial pressure</measure>
      <time_frame>8 weeks</time_frame>
      <description>Change in lumbar opening pressure in cm cerebrospinal fluid measured by manometry</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Intracranial pressure</measure>
      <time_frame>8 weeks</time_frame>
      <description>Change in lumbar opening pressure (%)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Weight</measure>
      <time_frame>10 months</time_frame>
      <description>Weight change (%)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Intracranial Pressure</measure>
      <time_frame>10 months</time_frame>
      <description>Change in lumbar opening pressure in cm cerebrospinal fluid measured by manometry</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Intracranial Pressure</measure>
      <time_frame>10 months</time_frame>
      <description>Change in lumbar opening pressure (%)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Quality of Life</measure>
      <time_frame>8 weeks + 10 months</time_frame>
      <description>Change in total score of Quality of Life (psychological, social, physical, environmental) assessed by the World Health Organization Quality of Life Brief Version Questionnaire (0-100; 0 worst, 100 best)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Headache burden measured by HURT questionnaire</measure>
      <time_frame>8 weeks + 10 months</time_frame>
      <description>Change in summation of scores in the questionnaire &quot;Headache Under Response to Treatment Questionnaire&quot; (HURT); 0-24 points were higher numbers are worse outcome</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Papilledema</measure>
      <time_frame>8 weeks + 10 months</time_frame>
      <description>Change in Frisén Grade (0-5, 0 minimal, 5 worst)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Visual fields</measure>
      <time_frame>8 weeks + 10 months</time_frame>
      <description>Perimetric mean deviation (decibel) by Humphrey automated perimetry</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>EDI-OCT</measure>
      <time_frame>8 weeks + 10 months</time_frame>
      <description>Change in Papillary thickness (um) measured by Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Optic disc elevation</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Optic disc elevation (mm) measured by transorbital ultrasonography, (average of 3 scans of each eye with papilledema)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Remission</measure>
      <time_frame>8 weeks + 10 months</time_frame>
      <description>Proportion of patients with abscence of papilledema with or without intracranial pressure &lt;25 cm cerebrospinal fluid</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in fat mass</measure>
      <time_frame>8 weeks + 10 months</time_frame>
      <description>Change in body fat percentage measured by Dual Energy X-ray Absorptiometry compared to baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Total fat mass</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Body fat percentage measured by Dual Energy X-ray Absorptiometry</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Feasibility</measure>
      <time_frame>8 weeks + 10 months</time_frame>
      <description>Drop-out rate (proportion of patients withdrawing from participation)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Need of intracranial pressure-lowering medication_1</measure>
      <time_frame>8 weeks + 10 months</time_frame>
      <description>Dose (mg) of intracranial pressure-lowering medication needed (Acetazolamide, Topiramate, diuretics)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Fatty liver prevalence</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Prevalence of non-alcoholic fatty liver disease evaluated by ultrasonography (subjectively assessed density of liver parenchyma compared to hepatic perivascular density and renal density), assessed by an experienced radiologist with specialization in ultrasonography</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Monthly headache days</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Number of days with headache for the past 30 days preceding visit</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Headche severity</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Number of days with mild, moderate, and severy headache, respectively, in the past 30 days preceding visit</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Headache medication - Acute analgesic use</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Number of days with need of acute analgesic treatment for headache</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Headache medication - preventive medication</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Need of preventive medical treatment for headache</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Optic nerve sheath diameter</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Optic nerve sheath diameter (mm) measured by transorbital ultrasonography (average of 3 scans of each eye with papilledema)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Peripapillary capillary density</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Change in peripapillary capillary density (ratio of pixels of perpapillary vessels and pixels in the foveal area evaluated by Optic Coherence Tomography Angiography</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Peripapillary artery-to-venule ratio</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Change in peripapillary artery-to-venule diameter ratio measured by confocal Scanning Laser Ophtalmoscopy</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Truncal fat</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Change in percentage of truncal adiposity measured by Dual Energy X-ray Absorptiometry</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Android-gynoid-ratio</measure>
      <time_frame>Baseline + 8 weeks and 10 months</time_frame>
      <description>Change in ratio of Android versus gynoid fat percentage using Dual Energy X-ray Absorptiometry</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse events</measure>
      <time_frame>8 weeks + 10 months</time_frame>
      <description>Number of adverse events overall, and sub-categorized into adverse events (AE) (any event happening during attachment to the project) and severe adverse events (SAE) in case of the following conditions: Hospitalization or prolongation of hospitalization, death, life-threatening or significant disability/incapacity</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Need of intracranial pressure-lowering medication_2</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Number of patients in need of any intracranial pressure-lowering drug (Acetazolamide, Topiramate, diuretics)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Insulin like-Growth-Factor-1</measure>
      <time_frame>Baseline</time_frame>
      <description>Level of Insulin like-Growth-Factor-1 in serum (ug/L) in women not taking estrogen-containing contraceptives.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Insulinlike Growth Factor Binding Protein-3</measure>
      <time_frame>Baseline</time_frame>
      <description>Level of Insulinlike Growth Factor Binding Protein-3 in serum (ug/L) in women not taking estrogen-containing contraceptives.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Growth hormone</measure>
      <time_frame>Baseline</time_frame>
      <description>Level of growth hormone in serum ug(L) in women not taking estrogen-containing contraceptives.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Lutropin</measure>
      <time_frame>Baseline</time_frame>
      <description>Level of Lutropin in serum (IU/L) in women not taking estrogen-containing contraceptives.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Follitropin</measure>
      <time_frame>Baseline</time_frame>
      <description>Level of Follitropin in serum (IU/L) in women not taking estrogen-containing contraceptives.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Testosteron</measure>
      <time_frame>Baseline</time_frame>
      <description>Level of testosteron in serum (nmol/L) in women not taking estrogen-containing contraceptives.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Estradiol</measure>
      <time_frame>Baseline</time_frame>
      <description>Level of estradiol in serum (nmol/L) in women not taking estrogen-containing contraceptives.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Sex-Hormone Binding Globulin</measure>
      <time_frame>Baseline</time_frame>
      <description>Level of Sex-Hormone Binding Globulin in serum (nmol/L) in women not taking estrogen-containing contraceptives.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Anti-Müllerian Hormone</measure>
      <time_frame>Baseline</time_frame>
      <description>Level of Anti-Müllerian Hormone (pmol/L) in serum in women not taking estrogen-containing contraceptives.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dehydroepiandrosterone</measure>
      <time_frame>Baseline</time_frame>
      <description>Level of Dehydroepiandrosterone (DHEAS) in serum (umol/L) in women not taking estrogen-containing contraceptives.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Androstenedion</measure>
      <time_frame>Baseline</time_frame>
      <description>Level of androstenedion (nmol/L) in serum in women not taking estrogen-containing contraceptives.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>17-hydroxyprogesterone (mg/d)</measure>
      <time_frame>Baseline</time_frame>
      <description>Level of 17-hydroxyprogesterone (mg/d) in serum in women not taking estrogen-containing contraceptives.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cortisol 0 min</measure>
      <time_frame>Baseline</time_frame>
      <description>Level of cortisol (nmol/L) in serum in women not taking estrogen-containing contraceptives.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cortisol 30 min</measure>
      <time_frame>Baseline</time_frame>
      <description>Level of cortisol (nmol/L) in serum 30 minutes after stimulation with 0,25 mg SynACHTen in women not taking estrogen-containing contraceptives.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pituitary adenylate cyclase-activating peptide (PACAP) Pituitary adenylate cyclase-activating peptide Pituitary adenylate cyclase-activating peptide</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Level (picograms per milliliter in plasma and cerebrospinal fluid) of Pituitary adenylate cyclase-activating peptide (PACAP)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Calcitonin Gene Related Peptide</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Calcitonin Gene Related Peptide (CGRP) level pg/mL (picograms per milliliter in plasma and cerebrospinal fluid)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in bone marker (CTX)</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Change in carboxy-terminal collagen crosslinks (CTX) level (nanograms per liter)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in bone marker (PiNP)</measure>
      <time_frame>baseline + 8 weeks + 10 months</time_frame>
      <description>Change in procollagen type I N-propeptide (PiNP) level (micrograms per liter) compared to baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Regional bone density</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Change in regional bone density in grams/square cm (g/cm2) and T- and Z-scores of hip and spine measured by Dual Energy X-ray Absorptiometry compared to baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Androgen metabolism_1</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Ratio between Etiocholanolone and Androsterone (ng/mg) in 24-hour urine</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Androgen metabolism_2</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Ratio between 5-alpha-tetrahydrocortisol (5a-THF) and tetrahydrocortisol (THF) in 24-hour urine</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Androgen metabolism_3</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Level of testosterone in 24-hour urine (ng/L)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Androgen metabolism_4</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Level of 3-alpha-androstanediol in 24-hour urine (nmol/L)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Androgen metabolism_5</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Level of 11-oxygenated androgens (11-OHA4) (pg/L) in 24-hour urine</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Intrathecal Semaglutide</measure>
      <time_frame>10 months</time_frame>
      <description>Level of semaglutide in cerebrospinal fluid (picomol/L)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ammoniaemia_1</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Levels of plasma ammonium (umol/L)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ammoniaemia_2</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Correlation between plasma ammonium (umol/L) and presence of fatty liver disease as indicated by liver ultrasonography</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ketosis</measure>
      <time_frame>8 weeks + 10 months</time_frame>
      <description>Proportion of patients in ketosis measured by urine stix</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in metabolic parameters</measure>
      <time_frame>8 weeks + 10 months</time_frame>
      <description>Change in Homeostatic Model for Insulin Resistance (HOMA2IR) compared to baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in metabolic parameters</measure>
      <time_frame>8 weeks + 10 months</time_frame>
      <description>Change in glycated hemoglobin (mmol/mol) compared to baseline</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Omics</measure>
      <time_frame>Baseline + 8 weeks + 10 months</time_frame>
      <description>Metabolomic and proteomic profile, exploratory analyses</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">50</enrollment>
    <condition>Idiopathic Intracranial Hypertension</condition>
    <condition>Intracranial Pressure</condition>
    <condition>Obesity</condition>
    <condition>Pseudotumor Cerebri Syndrome</condition>
    <condition>Papilledema</condition>
    <condition>Weight Loss</condition>
    <arm_group>
      <arm_group_label>Semaglutide</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Semaglutide up-titration to 2.4 mg for 10 months initially combined with a Very Low Calorie Diet (800 kcal/day) for 8 weeks.&#xD;
  Counselling by dietician Standard medical treatment of intracranial hypertension</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Standard care (dietician)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Standard weight loss intervention Counselling by dietician Standard medical treatment of intracranial hypertension</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Semaglutide</intervention_name>
      <description>Subcutaneous once-weekly injections of Semaglutide uptitrating to a maximum of 2.4 mg</description>
      <arm_group_label>Semaglutide</arm_group_label>
      <other_name>Ozempic, Wegovy</other_name>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Very Low Calorie Diet</intervention_name>
      <description>Very Low Calorie Diet (max 800 kcal/day) using Nupo Diet meal replacement products</description>
      <arm_group_label>Semaglutide</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Dietician counselling</intervention_name>
      <description>Counselling by a dietician on weight loss through behavioural changes and life style intervention</description>
      <arm_group_label>Semaglutide</arm_group_label>
      <arm_group_label>Standard care (dietician)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Confirmed new onset definite IIH with papilledema and lumbar opening pressure ≥25 cm&#xD;
               cerebrospinal fluid according to Friedmann diagnostic criteria&#xD;
  &#xD;
            -  BMI ≥ 27&#xD;
  &#xD;
            -  Use of contraceptive methods with failure rates of less than 1 % throughout the study&#xD;
               period for group A and for at least an additional 2 months after cessation of&#xD;
               Semaglutide&#xD;
  &#xD;
            -  Written, informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Unable to provide written informed consent or participate&#xD;
  &#xD;
            -  Malignant IIH with visual threat that requires surgical intervention, i.e.,&#xD;
               cerebrospinal fluid diversion (shunting), optic nerve sheet fenestration or cerebral&#xD;
               venous sinus stenting&#xD;
  &#xD;
            -  Pregnancy or breastfeeding&#xD;
  &#xD;
            -  Treatment with antidiabetics, blood-thinners or medication that may increase the risk&#xD;
               of adverse events&#xD;
  &#xD;
            -  Diabetes, congestive heart failure, severe vascular disease, pancreatitis, severe&#xD;
               ophthalmological disorders other than IIH (e.g. retinopathy)&#xD;
  &#xD;
            -  History or family history of thyroid carcinomas or Multiple Endocrine Neoplasias&#xD;
               (MEN1/MEN2)&#xD;
  &#xD;
            -  History of bariatric surgery&#xD;
  &#xD;
            -  Known hypersensitivity to any contents of Semaglutide®&#xD;
  &#xD;
            -  Other severe/uncontrolled mental or physical disease&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Rigmor H Jensen, Professor</last_name>
      <role>Study Director</role>
      <affiliation>Danish Headache Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Rigmor H Jensen, Professor</last_name>
      <phone>0045-38633059</phone>
      <email>rigmor.jensen@regionh.dk</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Nadja Skadkær Hansen, MD</last_name>
      <phone>0045-38633553</phone>
      <email>nadja.skadkaer.hansen@regionh.dk</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Danish Headache Center, Department of Neurology, Rigshospitalet</name>
        <address>
          <city>Glostrup</city>
          <zip>2600</zip>
          <country>Denmark</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Nadja S Hansen, MD</last_name>
        <phone>0045-38633553</phone>
        <email>nadja.skadkaer.hansen@regionh.dk</email>
      </contact>
      <contact_backup>
        <last_name>Rigmor H Jensen, Professor</last_name>
        <phone>0045-38633059</phone>
        <email>rigmor.jensen@regionh.dk</email>
      </contact_backup>
      <investigator>
        <last_name>Nadja S Hansen, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Headache clinic, Department of Neurology, Odense University Hospital</name>
        <address>
          <city>Odense</city>
          <zip>5000</zip>
          <country>Denmark</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Dagmar Beier, MD</last_name>
        <phone>0045-65415604</phone>
        <email>dagmar.beier@rsyd.dk</email>
      </contact>
      <investigator>
        <last_name>Dagmar Beier, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Denmark</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>February 23, 2023</study_first_submitted>
    <study_first_submitted_qc>September 6, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 7, 2023</study_first_posted>
    <last_update_submitted>September 7, 2023</last_update_submitted>
    <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Danish Headache Center</investigator_affiliation>
      <investigator_full_name>Rigmor Højland Jensen</investigator_full_name>
      <investigator_title>Professor in Neurology</investigator_title>
    </responsible_party>
    <keyword>Idiopathic Intracranial Hypertension</keyword>
    <keyword>Papilledema</keyword>
    <keyword>Weight loss</keyword>
    <keyword>Obesity</keyword>
    <keyword>Pseudotumor Cerebri Syndrome</keyword>
    <keyword>Intracranial Pressure</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Intracranial Hypertension</mesh_term>
      <mesh_term>Pseudotumor Cerebri</mesh_term>
      <mesh_term>Papilledema</mesh_term>
      <mesh_term>Hypertension</mesh_term>
      <mesh_term>Obesity</mesh_term>
      <mesh_term>Body Weight</mesh_term>
      <mesh_term>Weight Loss</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </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/NCT06027567
  org study id: IIH:DUAL
  nct id: NCT06027567
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  50 patients with verified new-onset Idiopathic Intracranial Hypertension are randomly
        allocated to standard weight management (dietician counselling) or trial intervention
        consisting of subcutaneous injections with Semaglutide for 10 months combined, in the initial
        8 weeks following diagnosis, with a Very Low Calorie-Diet (max 800 kcal/day)
  Idiopathic Intracranial Hypertension is primarily observed in obese female and weight
        management promotes disease control by yet unsettled mechanisms. Effective, fast and lasting
        weight loss is crucial, however, hard to achieve. Current weight management strategy in IIH
        in Denmark is counselling by a dietician. This study investigates whether an initial Very Low
        Calorie Diet (max 800 kcal/day) for 8 weeks following the diagnosis combined with GLP1-RA
        treatment throughout 10 months is tolerated and more efficient in achieving substantial
        weight loss and reduction of intracranial pressure. Furthermore, a number of secondary
        outcomes are measured including headache burden, quality of life, structure and function of
        the optic nerve, non-invasive surrogate markers of intracranial pressure, body fat mass, bone
        health, fatty liver disease and a range of cerebrospinal-, blood- and urine markers of i.a.
        the hormonal, inflammatory, metabolic, and headache biomarker profile.
  
        The intervention may candidate as a future first-line treatment regime.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Open label randomized controlled clinical treatment trial Patients are randomly assigned 1:1 to standard-of-care or intervention
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Weight
  time frame: 8 weeks
  description: Weight change (%)
  measure: Intracranial pressure
  time frame: 8 weeks
  description: Change in lumbar opening pressure in cm cerebrospinal fluid measured by manometry
  measure: Intracranial pressure
  time frame: 8 weeks
  description: Change in lumbar opening pressure (%)
  measure: Weight
  time frame: 10 months
  description: Weight change (%)
  measure: Intracranial Pressure
  time frame: 10 months
  description: Change in lumbar opening pressure in cm cerebrospinal fluid measured by manometry
  measure: Intracranial Pressure
  time frame: 10 months
  description: Change in lumbar opening pressure (%)
  measure: Quality of Life
  time frame: 8 weeks + 10 months
  description: Change in total score of Quality of Life (psychological, social, physical, environmental) assessed by the World Health Organization Quality of Life Brief Version Questionnaire (0-100; 0 worst, 100 best)
  measure: Headache burden measured by HURT questionnaire
  time frame: 8 weeks + 10 months
  description: Change in summation of scores in the questionnaire "Headache Under Response to Treatment Questionnaire" (HURT); 0-24 points were higher numbers are worse outcome
  measure: Change in Papilledema
  time frame: 8 weeks + 10 months
  description: Change in Frisén Grade (0-5, 0 minimal, 5 worst)
  measure: Visual fields
  time frame: 8 weeks + 10 months
  description: Perimetric mean deviation (decibel) by Humphrey automated perimetry
  measure: EDI-OCT
  time frame: 8 weeks + 10 months
  description: Change in Papillary thickness (um) measured by Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT)
  measure: Optic disc elevation
  time frame: Baseline + 8 weeks + 10 months
  description: Optic disc elevation (mm) measured by transorbital ultrasonography, (average of 3 scans of each eye with papilledema)
  measure: Remission
  time frame: 8 weeks + 10 months
  description: Proportion of patients with abscence of papilledema with or without intracranial pressure <25 cm cerebrospinal fluid
  measure: Change in fat mass
  time frame: 8 weeks + 10 months
  description: Change in body fat percentage measured by Dual Energy X-ray Absorptiometry compared to baseline
  measure: Total fat mass
  time frame: Baseline + 8 weeks + 10 months
  description: Body fat percentage measured by Dual Energy X-ray Absorptiometry
  measure: Feasibility
  time frame: 8 weeks + 10 months
  description: Drop-out rate (proportion of patients withdrawing from participation)
  measure: Need of intracranial pressure-lowering medication_1
  time frame: 8 weeks + 10 months
  description: Dose (mg) of intracranial pressure-lowering medication needed (Acetazolamide, Topiramate, diuretics)
  measure: Fatty liver prevalence
  time frame: Baseline + 8 weeks + 10 months
  description: Prevalence of non-alcoholic fatty liver disease evaluated by ultrasonography (subjectively assessed density of liver parenchyma compared to hepatic perivascular density and renal density), assessed by an experienced radiologist with specialization in ultrasonography
  measure: Monthly headache days
  time frame: Baseline + 8 weeks + 10 months
  description: Number of days with headache for the past 30 days preceding visit
  measure: Headche severity
  time frame: Baseline + 8 weeks + 10 months
  description: Number of days with mild, moderate, and severy headache, respectively, in the past 30 days preceding visit
  measure: Headache medication - Acute analgesic use
  time frame: Baseline + 8 weeks + 10 months
  description: Number of days with need of acute analgesic treatment for headache
  measure: Headache medication - preventive medication
  time frame: Baseline + 8 weeks + 10 months
  description: Need of preventive medical treatment for headache
  measure: Optic nerve sheath diameter
  time frame: Baseline + 8 weeks + 10 months
  description: Optic nerve sheath diameter (mm) measured by transorbital ultrasonography (average of 3 scans of each eye with papilledema)
  measure: Peripapillary capillary density
  time frame: Baseline + 8 weeks + 10 months
  description: Change in peripapillary capillary density (ratio of pixels of perpapillary vessels and pixels in the foveal area evaluated by Optic Coherence Tomography Angiography
  measure: Peripapillary artery-to-venule ratio
  time frame: Baseline + 8 weeks + 10 months
  description: Change in peripapillary artery-to-venule diameter ratio measured by confocal Scanning Laser Ophtalmoscopy
  measure: Truncal fat
  time frame: Baseline + 8 weeks + 10 months
  description: Change in percentage of truncal adiposity measured by Dual Energy X-ray Absorptiometry
  measure: Android-gynoid-ratio
  time frame: Baseline + 8 weeks and 10 months
  description: Change in ratio of Android versus gynoid fat percentage using Dual Energy X-ray Absorptiometry
  measure: Adverse events
  time frame: 8 weeks + 10 months
  description: Number of adverse events overall, and sub-categorized into adverse events (AE) (any event happening during attachment to the project) and severe adverse events (SAE) in case of the following conditions: Hospitalization or prolongation of hospitalization, death, life-threatening or significant disability/incapacity
  measure: Need of intracranial pressure-lowering medication_2
  time frame: Baseline + 8 weeks + 10 months
  description: Number of patients in need of any intracranial pressure-lowering drug (Acetazolamide, Topiramate, diuretics)
  measure: Insulin like-Growth-Factor-1
  time frame: Baseline
  description: Level of Insulin like-Growth-Factor-1 in serum (ug/L) in women not taking estrogen-containing contraceptives.
  measure: Insulinlike Growth Factor Binding Protein-3
  time frame: Baseline
  description: Level of Insulinlike Growth Factor Binding Protein-3 in serum (ug/L) in women not taking estrogen-containing contraceptives.
  measure: Growth hormone
  time frame: Baseline
  description: Level of growth hormone in serum ug(L) in women not taking estrogen-containing contraceptives.
  measure: Lutropin
  time frame: Baseline
  description: Level of Lutropin in serum (IU/L) in women not taking estrogen-containing contraceptives.
  measure: Follitropin
  time frame: Baseline
  description: Level of Follitropin in serum (IU/L) in women not taking estrogen-containing contraceptives.
  measure: Testosteron
  time frame: Baseline
  description: Level of testosteron in serum (nmol/L) in women not taking estrogen-containing contraceptives.
  measure: Estradiol
  time frame: Baseline
  description: Level of estradiol in serum (nmol/L) in women not taking estrogen-containing contraceptives.
  measure: Sex-Hormone Binding Globulin
  time frame: Baseline
  description: Level of Sex-Hormone Binding Globulin in serum (nmol/L) in women not taking estrogen-containing contraceptives.
  measure: Anti-Müllerian Hormone
  time frame: Baseline
  description: Level of Anti-Müllerian Hormone (pmol/L) in serum in women not taking estrogen-containing contraceptives.
  measure: Dehydroepiandrosterone
  time frame: Baseline
  description: Level of Dehydroepiandrosterone (DHEAS) in serum (umol/L) in women not taking estrogen-containing contraceptives.
  measure: Androstenedion
  time frame: Baseline
  description: Level of androstenedion (nmol/L) in serum in women not taking estrogen-containing contraceptives.
  measure: 17-hydroxyprogesterone (mg/d)
  time frame: Baseline
  description: Level of 17-hydroxyprogesterone (mg/d) in serum in women not taking estrogen-containing contraceptives.
  measure: Cortisol 0 min
  time frame: Baseline
  description: Level of cortisol (nmol/L) in serum in women not taking estrogen-containing contraceptives.
  measure: Cortisol 30 min
  time frame: Baseline
  description: Level of cortisol (nmol/L) in serum 30 minutes after stimulation with 0,25 mg SynACHTen in women not taking estrogen-containing contraceptives.
  measure: Pituitary adenylate cyclase-activating peptide (PACAP) Pituitary adenylate cyclase-activating peptide Pituitary adenylate cyclase-activating peptide
  time frame: Baseline + 8 weeks + 10 months
  description: Level (picograms per milliliter in plasma and cerebrospinal fluid) of Pituitary adenylate cyclase-activating peptide (PACAP)
  measure: Calcitonin Gene Related Peptide
  time frame: Baseline + 8 weeks + 10 months
  description: Calcitonin Gene Related Peptide (CGRP) level pg/mL (picograms per milliliter in plasma and cerebrospinal fluid)
  measure: Change in bone marker (CTX)
  time frame: Baseline + 8 weeks + 10 months
  description: Change in carboxy-terminal collagen crosslinks (CTX) level (nanograms per liter)
  measure: Change in bone marker (PiNP)
  time frame: baseline + 8 weeks + 10 months
  description: Change in procollagen type I N-propeptide (PiNP) level (micrograms per liter) compared to baseline
  measure: Regional bone density
  time frame: Baseline + 8 weeks + 10 months
  description: Change in regional bone density in grams/square cm (g/cm2) and T- and Z-scores of hip and spine measured by Dual Energy X-ray Absorptiometry compared to baseline
  measure: Androgen metabolism_1
  time frame: Baseline + 8 weeks + 10 months
  description: Ratio between Etiocholanolone and Androsterone (ng/mg) in 24-hour urine
  measure: Androgen metabolism_2
  time frame: Baseline + 8 weeks + 10 months
  description: Ratio between 5-alpha-tetrahydrocortisol (5a-THF) and tetrahydrocortisol (THF) in 24-hour urine
  measure: Androgen metabolism_3
  time frame: Baseline + 8 weeks + 10 months
  description: Level of testosterone in 24-hour urine (ng/L)
  measure: Androgen metabolism_4
  time frame: Baseline + 8 weeks + 10 months
  description: Level of 3-alpha-androstanediol in 24-hour urine (nmol/L)
  measure: Androgen metabolism_5
  time frame: Baseline + 8 weeks + 10 months
  description: Level of 11-oxygenated androgens (11-OHA4) (pg/L) in 24-hour urine
  measure: Intrathecal Semaglutide
  time frame: 10 months
  description: Level of semaglutide in cerebrospinal fluid (picomol/L)
  measure: Ammoniaemia_1
  time frame: Baseline + 8 weeks + 10 months
  description: Levels of plasma ammonium (umol/L)
  measure: Ammoniaemia_2
  time frame: Baseline + 8 weeks + 10 months
  description: Correlation between plasma ammonium (umol/L) and presence of fatty liver disease as indicated by liver ultrasonography
  measure: Ketosis
  time frame: 8 weeks + 10 months
  description: Proportion of patients in ketosis measured by urine stix
  measure: Change in metabolic parameters
  time frame: 8 weeks + 10 months
  description: Change in Homeostatic Model for Insulin Resistance (HOMA2IR) compared to baseline
  measure: Change in metabolic parameters
  time frame: 8 weeks + 10 months
  description: Change in glycated hemoglobin (mmol/mol) compared to baseline
  measure: Omics
  time frame: Baseline + 8 weeks + 10 months
  description: Metabolomic and proteomic profile, exploratory analyses
  arm group label: Semaglutide
  arm group type: Experimental
  description: Semaglutide up-titration to 2.4 mg for 10 months initially combined with a Very Low Calorie Diet (800 kcal/day) for 8 weeks.
  Counselling by dietician Standard medical treatment of intracranial hypertension
  arm group label: Standard care (dietician)
  arm group type: Active Comparator
  description: Standard weight loss intervention Counselling by dietician Standard medical treatment of intracranial hypertension
  intervention type: Drug
  intervention name: Semaglutide
  description: Subcutaneous once-weekly injections of Semaglutide uptitrating to a maximum of 2.4 mg
  arm group label: Semaglutide
  other name: Ozempic, Wegovy
  intervention type: Dietary Supplement
  intervention name: Very Low Calorie Diet
  description: Very Low Calorie Diet (max 800 kcal/day) using Nupo Diet meal replacement products
  arm group label: Semaglutide
  intervention type: Behavioral
  intervention name: Dietician counselling
  description: Counselling by a dietician on weight loss through behavioural changes and life style intervention
  arm group label: Semaglutide
  arm group label: Standard care (dietician)
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Rigmor H Jensen, Professor
  role: Study Director
  affiliation: Danish Headache Center
  last name: Rigmor H Jensen, Professor
  phone: 0045-38633059
  email: rigmor.jensen@regionh.dk
  last name: Nadja Skadkær Hansen, MD
  phone: 0045-38633553
  email: nadja.skadkaer.hansen@regionh.dk
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  facility: 
  status: Not yet recruiting
  contact: 
  investigator: 
  country: Denmark
  responsible party type: Sponsor-Investigator
  investigator affiliation: Danish Headache Center
  investigator full name: Rigmor Højland Jensen
  investigator title: Professor in Neurology
  mesh term: Intracranial Hypertension
  mesh term: Pseudotumor Cerebri
  mesh term: Papilledema
  mesh term: Hypertension
  mesh term: Obesity
  mesh term: Body Weight
  mesh term: Weight Loss
  sharing ipd: No