<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/NCT03253120</url>
  </required_header>
  <id_info>
    <org_study_id>2017-01368</org_study_id>
    <nct_id>NCT03253120</nct_id>
  </id_info>
  <brief_title>Alterations of Attention in POTS Depending on Body Position and Hydration</brief_title>
  <official_title>Alterations of Attention in Patients With Postural Tachycardia Syndrome and Healthy Controls Depending on Body Position and Hydration</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Insel Gruppe AG, University Hospital Bern</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Insel Gruppe AG, University Hospital Bern</source>
  <oversight_info>
    <has_dmc>No</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 Postural Tachycardia-Syndrome (POTS) is a form of autonomic dysregulation, typically&#xD;
      accompanied by symptoms of orthostatic intolerance (OI). OI is defined by the inability to&#xD;
      tolerate the upright position and is improved by lying down. POTS is considered a syndrome&#xD;
      that may include a number of several disorders. Symptoms should be persistent for at least 6&#xD;
      months to reach a diagnosis. It is characterized by a sustained heart rate (HR) increment of&#xD;
      30 beats/min or more within 10 min of standing or head-up tilt (HUT) in adults, in the&#xD;
      absence of orthostatic hypotension and with the presence of symptoms of OI. In children and&#xD;
      adolescents a diagnosis requests a HR increment of at least 40 beats/min. The increment in HR&#xD;
      when moving to an upright posture is often a response to a reduction in venous return,&#xD;
      causing excessive blood pooling in the lower limbs. The symptoms present in POTS vary&#xD;
      greatly. Typical symptoms are lightheadedness, dizziness, blurred vision, mental clouding&#xD;
      (&quot;brain fog&quot;) or cognitive dysfunction. Other symptoms may present as palpitations or chest&#xD;
      pain. Additional symptoms consist of postural headaches, nausea, sleep disturbances, fatigue&#xD;
      and gastrointestinal dysfunction. The manifestation of symptoms in POTS varies in severity,&#xD;
      frequency and combination, resulting in POTS being a very heterogenous and subjective&#xD;
      disorder. Symptoms can be severe and often make simple daily activities difficult to an&#xD;
      extent that compromises the patients quality of life. Typically symptoms exacerbate in the&#xD;
      mornings, after physical activity, after eating and during menstruation.&#xD;
&#xD;
      This study objective is to examine the occurrence, mechanisms and causes of impaired&#xD;
      attention in POTS as well as to test the effect of acute water ingestion for attention in&#xD;
      POTS. The investigators therefore conduct a study including patients with POTS and healthy&#xD;
      volunteers.&#xD;
&#xD;
      All participants will receive a dossier of five self-assessment questionnaires after giving&#xD;
      informed consent. Clinical examination includes 2 HUT-tests while standing for 15 minutes,&#xD;
      conventional measuring of blood pressure, continuous recording of NIRS signals during&#xD;
      testing, determination of pupil size, the diameter of the optic nerve and Neuropsychological&#xD;
      testing (Test of Attentional Performance, mobility version&quot; (TAP-M), Go/NoGo Test, Divided&#xD;
      Attention Test)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background&#xD;
&#xD;
      Postural Tachycardia Syndrome (POTS) is a form of autonomic dysregulation, typically&#xD;
      accompanied by symptoms of orthostatic intolerance (OI). OI is defined by the inability to&#xD;
      tolerate the upright position and is improved by lying down. POTS is considered a syndrome&#xD;
      that may include a number of several disorders. Symptoms should be persistent for at least 6&#xD;
      months to reach a diagnosis. It is characterized by a sustained heart rate (HR) increment of&#xD;
      30 beats/min or more within 10 min of standing or head-up tilt (HUT) in adults, in the&#xD;
      absence of orthostatic hypotension and with the presence of symptoms of OI. In children and&#xD;
      adolescents diagnosis requests a HR increment of at least 40 beats/min. The increment in HR&#xD;
      when moving to an upright posture is often caused by a reduction in venous return because of&#xD;
      excessive blood pooling in the lower limbs. Clinical symptoms present in POTS vary greatly.&#xD;
      Typical symptoms are palpitations, lightheadedness, dizziness, blurred vision, mental&#xD;
      clouding (&quot;brain fog&quot;) or cognitive dysfunction . Additional symptoms consist of postural&#xD;
      headaches, nausea, but also non-orthostatic symptoms such as sleep disturbances, fatigue and&#xD;
      gastrointestinal dysfunction. The manifestation of symptoms in POTS varies in severity,&#xD;
      frequency and combination, resulting in POTS being a very heterogenous and subjective&#xD;
      disorder. Symptoms can be severe and make simple daily activities difficult. Typically&#xD;
      symptoms exacerbate in the mornings, after physical activity, after eating and during&#xD;
      menstruation. The onset of the syndrome is associated with a variety of possible causes, e.g.&#xD;
      a recent viral illness or autonomic neuropathy.&#xD;
&#xD;
      As mentioned above, some of the most frequent reported symptoms are concentration- and&#xD;
      attentional problems so called &quot;brain fog&quot; or &quot;mental clouding&quot;. Previous research indicates&#xD;
      an actual deficit in cognitive functioning, which is, same as other POTS symptoms, exclusive&#xD;
      to the upright position. However, there is no overall accepted and recognized definition of&#xD;
      what &quot;brain fog&quot; is or what components it consists of. The majority of studies examined,&#xD;
      amongst other things, aspects of attention and working memory. Ross et al. compared it to&#xD;
      mental fatigue and showed that 67% of all POTS patients experience this symptom on a daily&#xD;
      basis, which indicates that routine daily activities and consequent quality of life are&#xD;
      reduced even further.&#xD;
&#xD;
      Conservative therapy in POTS consists in a high intake of water (2-3L) and salt on a daily&#xD;
      basis, wearing compression stockings and regular endurance training. Severely affected&#xD;
      patients may profit from additional drug treatment. A previous research group of the&#xD;
      investigators' unit showed in 2010 the improvement of OI in POTS after acute water and clear&#xD;
      soup intake.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      The purpose of this study is to examine the occurrence, mechanisms and causes of impaired&#xD;
      attention in POTS as well as to test the effect of acute water ingestion for attention in&#xD;
      POTS.&#xD;
&#xD;
      The study consists of four different assessments&#xD;
&#xD;
      Methode:&#xD;
&#xD;
      All participants will receive a dossier of five self-assessment questionnaires after giving&#xD;
      informed consent. The dossier consists of: Beck's Depression Inventory II (BDI-II) for&#xD;
      assessing depression, Short Form (36) Health Survey (SF-36) for assessing health-related&#xD;
      quality of life, Pittsburgh Sleep Quality Index (PSQI) for assessing sleep quality,&#xD;
      International Physical Activity Questionnaire (IPAQ) for assessing personal physical activity&#xD;
      and a questionnaire designed to measure specific symptoms in POTS (POTS Questionnaire) to&#xD;
      assess and objectify the symptomatology of POTS patients. The completion is expected to take&#xD;
      approximately one hour.&#xD;
&#xD;
      The study consists of four different assessments. For the examination all POTS medication&#xD;
      will be stopped prior to the examination. All participants have no dietary restrictions&#xD;
      during the days before the study, but will have to ingest nil by mouth after midnight.&#xD;
&#xD;
      For autonomic function testing, beat-to-beat BP and HR are measured (with the Finometer&#xD;
      device). At the beginning of each assessment, intermittent brachial BP and HR values will be&#xD;
      simultaneously recorded (using an automated Dinamap Pro 100 sphygmomanometer) on the right&#xD;
      arm. In addition, continuous recording of NIRS signals during testing will be acquired.&#xD;
&#xD;
      The study will start with a supine rest on an electrical tilt table for at least 10 minutes,&#xD;
      whilst BP and HR settle and sufficient correlation between Finometer and Dinamap readings are&#xD;
      achieved. A baseline assessment of attention in supine position follows, before tilting the&#xD;
      participants to a 60°upright position. In the upright position participants will again&#xD;
      perform the same assessment of attention. Patients will be at a tilt angle of 60° for a&#xD;
      maximum of 20 minutes. HUT will be terminated earlier in case of pre-syncope. After a short&#xD;
      recovery in the supine position, participants will be asked to drink 5 dl of commercially&#xD;
      available still mineral water within 5 minutes. To facilitate rapid drinking, the upper body&#xD;
      will be transiently elevated for 45-60°. After drinking, participants will again be supine&#xD;
      for 20 minutes before a second assessment of attention in the supine position. Subsequently&#xD;
      participants will again be tilted to 60° and complete the second assessment of attention in&#xD;
      the upright posture. HUT will be terminated earlier in case of pre-syncope. The duration of&#xD;
      tolerated HUT at baseline and after fluid ingestion will be noted.&#xD;
&#xD;
      Patients will be asked to rate their experienced symptoms in the upright position both before&#xD;
      and after the intake of water.&#xD;
&#xD;
      Neuropsychological testing will consist of three subtests of the automated computer-based&#xD;
      test battery &quot;Test of Attentional Performance, mobility version&quot; (TAP-M). Second the&#xD;
      investigators will use the &quot;Go/NoGo&quot; task for assessing the specific ability of subjects to&#xD;
      suppress undesired responses. Reaction times and errors are recorded in a simple test with&#xD;
      two stimuli. Using the subtest of &quot;Divided Attention&quot;, deficits of divided attention will be&#xD;
      measured, which are frequently diagnosed in neuropsychological practice. This can be assessed&#xD;
      in a &quot;dual-task&quot; paradigm, in which two stimuli have to be attended to simultaneously. The&#xD;
      test battery is computer-based; the screen will be placed in a distance of 30 cm from the&#xD;
      participants face and the button for reaction responses will be held in the dominant hand.&#xD;
      For capturing a possible decrease in attentional performance participants will complete the&#xD;
      sequence of the three subtests two times in two respective blocks, resulting in a total&#xD;
      duration time of 15 minutes.&#xD;
&#xD;
      The diameter of the optic nerve is measured with a 7-15 MHz linear array transducer in&#xD;
      transorbital B-mode ultrasound.&#xD;
&#xD;
      The investigators expect a study duration of approximately four hours.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 11, 2017</start_date>
  <completion_date type="Actual">July 5, 2022</completion_date>
  <primary_completion_date type="Actual">April 14, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Patients will drink 5dl of water. Healthy volunteers will drink 5dl of water.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Numerical variables reaction time and/or hits resp. misses in the subtests &quot;alertness&quot; from the automated test battery &quot;Test of Attentional Performance, mobility version&quot;</measure>
    <time_frame>After change body position and 5dl of water, up to 30 minutes</time_frame>
    <description>&quot;Alertness&quot; is designed to assess tonic alertness, which is defined as the ability to maintain a high level of responsiveness in anticipation of a test stimulus. The alertness test measures the simple reaction time in response to a visual stimulus (a cross presented on the monitor)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Numerical variables reaction time and/or hits resp. misses in the subtest &quot;Go/NoGo&quot; from the automated test battery &quot;Test of Attentional Performance, mobility version&quot;</measure>
    <time_frame>After change body position and 5dl of water, up to 30 minutes</time_frame>
    <description>The &quot;Go/NoGo&quot; task for assessing the specific ability of subjects to suppress undesired responses. Reaction times and errors are recorded in a simple test with two stimuli</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Numerical variables reaction time and/or hits resp. misses in the subtest &quot;divided attention&quot; from the automated test battery &quot;Test of Attentional Performance, mobility version&quot;</measure>
    <time_frame>After change body position and 5dl of water, up to 30 minutes</time_frame>
    <description>In the Test of Attentional Performance a visual and an auditory task must be processed in parallel</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Diameter of the optic nerve</measure>
    <time_frame>After change body position and 5dl of water, up to 30 minutes</time_frame>
    <description>The diameter of the optic nerve is measured with a 7-15 MHz linear array transducer in transorbital B-mode ultrasound .</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brain perfusion measured with NIRS</measure>
    <time_frame>After change body position and 5dl of water, up to 30 minutes</time_frame>
    <description>All parameters of brain perfusion will be assessed using NIRS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate</measure>
    <time_frame>After change body position and 5dl of water, up to 30 minutes</time_frame>
    <description>For autonomic function testing, beat-to-beat BP and HR are measured with the Finometer device.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>After change body position and 5dl of water, up to 30 minutes</time_frame>
    <description>For autonomic function testing, beat-to-beat BP and HR are measured with the Finometer device.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pupil diameter</measure>
    <time_frame>After change body position and 5dl of water, up to 30 minutes</time_frame>
    <description>Determination of pupil size will be performed with a rubber cup covering the measured eye and the operator's hand covering the nonmeasured eye. A brief 2- to 3-second pause allows the pupil to dilate briefly at which time the measurement will be taken. Pupil size is the average diameter for the entire measurement time, which is typically 3 to 4 seconds.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Scores of the questionnaires (composite endpoint)</measure>
    <time_frame>Through study completion an average of 1 day</time_frame>
    <description>Beck's Depression Inventory II (BDI-II) for assessing depression, Short Form (36) Health Survey (SF-36) for assessing health-related quality of life, Pittsburgh Sleep Quality Index (PSQI) for assessing sleep quality, International Physical Activity Questionaire</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Postural Tachycardia Syndrome</condition>
  <arm_group>
    <arm_group_label>Patient</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients will drink 5dl of water.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy volunteer</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Healthy volunteers will drink 5dl of water.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Water</intervention_name>
    <description>Patient/ Healthy volunteer will drink 5dl of Water</description>
    <arm_group_label>Healthy volunteer</arm_group_label>
    <arm_group_label>Patient</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        For patients:&#xD;
&#xD;
          -  Informed consent&#xD;
&#xD;
          -  Patients with diagnosed POTS (for criteria, see above)&#xD;
&#xD;
          -  Age: ≥18 years and ≤ 60 years&#xD;
&#xD;
        For healthy volunteers:&#xD;
&#xD;
          -  Informed consent&#xD;
&#xD;
          -  Age: ≥18 years and ≤ 60 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        For patients:&#xD;
&#xD;
          -  Pregnancy and Breastfeeding&#xD;
&#xD;
          -  Due to clinical reasons the current medication for POTS can not be discontinued&#xD;
&#xD;
        For healthy volunteers:&#xD;
&#xD;
          -  Pregnancy and Breastfeeding&#xD;
&#xD;
          -  Intake of vasoactive medication or known, non-treated arterial hypertension&#xD;
&#xD;
          -  Known vasovagal syncope in medical history&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Werner Z'Graggen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Inselspital Bern, Department of Neurosurgery and Neurology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Inselspital Bern</name>
      <address>
        <city>Bern</city>
        <zip>3010</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <reference>
    <citation>Anderson JW, Lambert EA, Sari CI, Dawood T, Esler MD, Vaddadi G, Lambert GW. Cognitive function, health-related quality of life, and symptoms of depression and anxiety sensitivity are impaired in patients with the postural orthostatic tachycardia syndrome (POTS). Front Physiol. 2014 Jun 25;5:230. doi: 10.3389/fphys.2014.00230. eCollection 2014.</citation>
    <PMID>25009504</PMID>
  </reference>
  <reference>
    <citation>Arnold AC, Haman K, Garland EM, Raj V, Dupont WD, Biaggioni I, Robertson D, Raj SR. Cognitive dysfunction in postural tachycardia syndrome. Clin Sci (Lond). 2015 Jan;128(1):39-45. doi: 10.1042/CS20140251.</citation>
    <PMID>25001527</PMID>
  </reference>
  <reference>
    <citation>Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, Cheshire WP, Chelimsky T, Cortelli P, Gibbons CH, Goldstein DS, Hainsworth R, Hilz MJ, Jacob G, Kaufmann H, Jordan J, Lipsitz LA, Levine BD, Low PA, Mathias C, Raj SR, Robertson D, Sandroni P, Schatz I, Schondorff R, Stewart JM, van Dijk JG. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res. 2011 Apr;21(2):69-72. doi: 10.1007/s10286-011-0119-5. No abstract available.</citation>
    <PMID>21431947</PMID>
  </reference>
  <reference>
    <citation>Lambert E, Lambert GW. Sympathetic dysfunction in vasovagal syncope and the postural orthostatic tachycardia syndrome. Front Physiol. 2014 Jul 28;5:280. doi: 10.3389/fphys.2014.00280. eCollection 2014.</citation>
    <PMID>25120493</PMID>
  </reference>
  <reference>
    <citation>Ocon AJ, Messer ZR, Medow MS, Stewart JM. Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome. Clin Sci (Lond). 2012 Mar;122(5):227-38. doi: 10.1042/CS20110241.</citation>
    <PMID>21919887</PMID>
  </reference>
  <reference>
    <citation>Raj SR. Postural tachycardia syndrome (POTS). Circulation. 2013 Jun 11;127(23):2336-42. doi: 10.1161/CIRCULATIONAHA.112.144501. No abstract available.</citation>
    <PMID>23753844</PMID>
  </reference>
  <reference>
    <citation>Z'Graggen WJ, Hess CW, Humm AM. Acute fluid ingestion in the treatment of orthostatic intolerance - important implications for daily practice. Eur J Neurol. 2010 Nov;17(11):1370-6. doi: 10.1111/j.1468-1331.2010.03030.x.</citation>
    <PMID>20412295</PMID>
  </reference>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 17, 2017</study_first_posted>
  <last_update_submitted>July 5, 2022</last_update_submitted>
  <last_update_submitted_qc>July 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 6, 2022</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>Postural Orthostatic Tachycardia Syndrome</mesh_term>
    <mesh_term>Tachycardia</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03253120
org study id: 2017-01368
nct id: NCT03253120
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The Postural Tachycardia-Syndrome (POTS) is a form of autonomic dysregulation, typically
      accompanied by symptoms of orthostatic intolerance (OI). OI is defined by the inability to
      tolerate the upright position and is improved by lying down. POTS is considered a syndrome
      that may include a number of several disorders. Symptoms should be persistent for at least 6
      months to reach a diagnosis. It is characterized by a sustained heart rate (HR) increment of
      30 beats/min or more within 10 min of standing or head-up tilt (HUT) in adults, in the
      absence of orthostatic hypotension and with the presence of symptoms of OI. In children and
      adolescents a diagnosis requests a HR increment of at least 40 beats/min. The increment in HR
      when moving to an upright posture is often a response to a reduction in venous return,
      causing excessive blood pooling in the lower limbs. The symptoms present in POTS vary
      greatly. Typical symptoms are lightheadedness, dizziness, blurred vision, mental clouding
      ("brain fog") or cognitive dysfunction. Other symptoms may present as palpitations or chest
      pain. Additional symptoms consist of postural headaches, nausea, sleep disturbances, fatigue
      and gastrointestinal dysfunction. The manifestation of symptoms in POTS varies in severity,
      frequency and combination, resulting in POTS being a very heterogenous and subjective
      disorder. Symptoms can be severe and often make simple daily activities difficult to an
      extent that compromises the patients quality of life. Typically symptoms exacerbate in the
      mornings, after physical activity, after eating and during menstruation.

      This study objective is to examine the occurrence, mechanisms and causes of impaired
      attention in POTS as well as to test the effect of acute water ingestion for attention in
      POTS. The investigators therefore conduct a study including patients with POTS and healthy
      volunteers.

      All participants will receive a dossier of five self-assessment questionnaires after giving
      informed consent. Clinical examination includes 2 HUT-tests while standing for 15 minutes,
      conventional measuring of blood pressure, continuous recording of NIRS signals during
      testing, determination of pupil size, the diameter of the optic nerve and Neuropsychological
      testing (Test of Attentional Performance, mobility version" (TAP-M), Go/NoGo Test, Divided
      Attention Test)
Background

      Postural Tachycardia Syndrome (POTS) is a form of autonomic dysregulation, typically
      accompanied by symptoms of orthostatic intolerance (OI). OI is defined by the inability to
      tolerate the upright position and is improved by lying down. POTS is considered a syndrome
      that may include a number of several disorders. Symptoms should be persistent for at least 6
      months to reach a diagnosis. It is characterized by a sustained heart rate (HR) increment of
      30 beats/min or more within 10 min of standing or head-up tilt (HUT) in adults, in the
      absence of orthostatic hypotension and with the presence of symptoms of OI. In children and
      adolescents diagnosis requests a HR increment of at least 40 beats/min. The increment in HR
      when moving to an upright posture is often caused by a reduction in venous return because of
      excessive blood pooling in the lower limbs. Clinical symptoms present in POTS vary greatly.
      Typical symptoms are palpitations, lightheadedness, dizziness, blurred vision, mental
      clouding ("brain fog") or cognitive dysfunction . Additional symptoms consist of postural
      headaches, nausea, but also non-orthostatic symptoms such as sleep disturbances, fatigue and
      gastrointestinal dysfunction. The manifestation of symptoms in POTS varies in severity,
      frequency and combination, resulting in POTS being a very heterogenous and subjective
      disorder. Symptoms can be severe and make simple daily activities difficult. Typically
      symptoms exacerbate in the mornings, after physical activity, after eating and during
      menstruation. The onset of the syndrome is associated with a variety of possible causes, e.g.
      a recent viral illness or autonomic neuropathy.

      As mentioned above, some of the most frequent reported symptoms are concentration- and
      attentional problems so called "brain fog" or "mental clouding". Previous research indicates
      an actual deficit in cognitive functioning, which is, same as other POTS symptoms, exclusive
      to the upright position. However, there is no overall accepted and recognized definition of
      what "brain fog" is or what components it consists of. The majority of studies examined,
      amongst other things, aspects of attention and working memory. Ross et al. compared it to
      mental fatigue and showed that 67% of all POTS patients experience this symptom on a daily
      basis, which indicates that routine daily activities and consequent quality of life are
      reduced even further.

      Conservative therapy in POTS consists in a high intake of water (2-3L) and salt on a daily
      basis, wearing compression stockings and regular endurance training. Severely affected
      patients may profit from additional drug treatment. A previous research group of the
      investigators' unit showed in 2010 the improvement of OI in POTS after acute water and clear
      soup intake.

      Objective:

      The purpose of this study is to examine the occurrence, mechanisms and causes of impaired
      attention in POTS as well as to test the effect of acute water ingestion for attention in
      POTS.

      The study consists of four different assessments

      Methode:

      All participants will receive a dossier of five self-assessment questionnaires after giving
      informed consent. The dossier consists of: Beck's Depression Inventory II (BDI-II) for
      assessing depression, Short Form (36) Health Survey (SF-36) for assessing health-related
      quality of life, Pittsburgh Sleep Quality Index (PSQI) for assessing sleep quality,
      International Physical Activity Questionnaire (IPAQ) for assessing personal physical activity
      and a questionnaire designed to measure specific symptoms in POTS (POTS Questionnaire) to
      assess and objectify the symptomatology of POTS patients. The completion is expected to take
      approximately one hour.

      The study consists of four different assessments. For the examination all POTS medication
      will be stopped prior to the examination. All participants have no dietary restrictions
      during the days before the study, but will have to ingest nil by mouth after midnight.

      For autonomic function testing, beat-to-beat BP and HR are measured (with the Finometer
      device). At the beginning of each assessment, intermittent brachial BP and HR values will be
      simultaneously recorded (using an automated Dinamap Pro 100 sphygmomanometer) on the right
      arm. In addition, continuous recording of NIRS signals during testing will be acquired.

      The study will start with a supine rest on an electrical tilt table for at least 10 minutes,
      whilst BP and HR settle and sufficient correlation between Finometer and Dinamap readings are
      achieved. A baseline assessment of attention in supine position follows, before tilting the
      participants to a 60°upright position. In the upright position participants will again
      perform the same assessment of attention. Patients will be at a tilt angle of 60° for a
      maximum of 20 minutes. HUT will be terminated earlier in case of pre-syncope. After a short
      recovery in the supine position, participants will be asked to drink 5 dl of commercially
      available still mineral water within 5 minutes. To facilitate rapid drinking, the upper body
      will be transiently elevated for 45-60°. After drinking, participants will again be supine
      for 20 minutes before a second assessment of attention in the supine position. Subsequently
      participants will again be tilted to 60° and complete the second assessment of attention in
      the upright posture. HUT will be terminated earlier in case of pre-syncope. The duration of
      tolerated HUT at baseline and after fluid ingestion will be noted.

      Patients will be asked to rate their experienced symptoms in the upright position both before
      and after the intake of water.

      Neuropsychological testing will consist of three subtests of the automated computer-based
      test battery "Test of Attentional Performance, mobility version" (TAP-M). Second the
      investigators will use the "Go/NoGo" task for assessing the specific ability of subjects to
      suppress undesired responses. Reaction times and errors are recorded in a simple test with
      two stimuli. Using the subtest of "Divided Attention", deficits of divided attention will be
      measured, which are frequently diagnosed in neuropsychological practice. This can be assessed
      in a "dual-task" paradigm, in which two stimuli have to be attended to simultaneously. The
      test battery is computer-based; the screen will be placed in a distance of 30 cm from the
      participants face and the button for reaction responses will be held in the dominant hand.
      For capturing a possible decrease in attentional performance participants will complete the
      sequence of the three subtests two times in two respective blocks, resulting in a total
      duration time of 15 minutes.

      The diameter of the optic nerve is measured with a 7-15 MHz linear array transducer in
      transorbital B-mode ultrasound.

      The investigators expect a study duration of approximately four hours.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Patients will drink 5dl of water. Healthy volunteers will drink 5dl of water.
primary purpose: Treatment
masking: None (Open Label)
measure: Numerical variables reaction time and/or hits resp. misses in the subtests "alertness" from the automated test battery "Test of Attentional Performance, mobility version"
time frame: After change body position and 5dl of water, up to 30 minutes
description: "Alertness" is designed to assess tonic alertness, which is defined as the ability to maintain a high level of responsiveness in anticipation of a test stimulus. The alertness test measures the simple reaction time in response to a visual stimulus (a cross presented on the monitor)
measure: Numerical variables reaction time and/or hits resp. misses in the subtest "Go/NoGo" from the automated test battery "Test of Attentional Performance, mobility version"
time frame: After change body position and 5dl of water, up to 30 minutes
description: The "Go/NoGo" task for assessing the specific ability of subjects to suppress undesired responses. Reaction times and errors are recorded in a simple test with two stimuli
measure: Numerical variables reaction time and/or hits resp. misses in the subtest "divided attention" from the automated test battery "Test of Attentional Performance, mobility version"
time frame: After change body position and 5dl of water, up to 30 minutes
description: In the Test of Attentional Performance a visual and an auditory task must be processed in parallel
measure: Diameter of the optic nerve
time frame: After change body position and 5dl of water, up to 30 minutes
description: The diameter of the optic nerve is measured with a 7-15 MHz linear array transducer in transorbital B-mode ultrasound .
measure: Brain perfusion measured with NIRS
time frame: After change body position and 5dl of water, up to 30 minutes
description: All parameters of brain perfusion will be assessed using NIRS.
measure: Heart rate
time frame: After change body position and 5dl of water, up to 30 minutes
description: For autonomic function testing, beat-to-beat BP and HR are measured with the Finometer device.
measure: Blood pressure
time frame: After change body position and 5dl of water, up to 30 minutes
description: For autonomic function testing, beat-to-beat BP and HR are measured with the Finometer device.
measure: Pupil diameter
time frame: After change body position and 5dl of water, up to 30 minutes
description: Determination of pupil size will be performed with a rubber cup covering the measured eye and the operator's hand covering the nonmeasured eye. A brief 2- to 3-second pause allows the pupil to dilate briefly at which time the measurement will be taken. Pupil size is the average diameter for the entire measurement time, which is typically 3 to 4 seconds.
measure: Scores of the questionnaires (composite endpoint)
time frame: Through study completion an average of 1 day
description: Beck's Depression Inventory II (BDI-II) for assessing depression, Short Form (36) Health Survey (SF-36) for assessing health-related quality of life, Pittsburgh Sleep Quality Index (PSQI) for assessing sleep quality, International Physical Activity Questionaire
arm group label: Patient
arm group type: Other
description: Patients will drink 5dl of water.
arm group label: Healthy volunteer
arm group type: Other
description: Healthy volunteers will drink 5dl of water.
intervention type: Other
intervention name: Water
description: Patient/ Healthy volunteer will drink 5dl of Water
arm group label: Healthy volunteer
arm group label: Patient
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Werner Z'Graggen, MD
role: Principal Investigator
affiliation: Inselspital Bern, Department of Neurosurgery and Neurology
facility: 
country: Switzerland
citation: Anderson JW, Lambert EA, Sari CI, Dawood T, Esler MD, Vaddadi G, Lambert GW. Cognitive function, health-related quality of life, and symptoms of depression and anxiety sensitivity are impaired in patients with the postural orthostatic tachycardia syndrome (POTS). Front Physiol. 2014 Jun 25;5:230. doi: 10.3389/fphys.2014.00230. eCollection 2014.
PMID: 25009504
citation: Arnold AC, Haman K, Garland EM, Raj V, Dupont WD, Biaggioni I, Robertson D, Raj SR. Cognitive dysfunction in postural tachycardia syndrome. Clin Sci (Lond). 2015 Jan;128(1):39-45. doi: 10.1042/CS20140251.
PMID: 25001527
citation: Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, Cheshire WP, Chelimsky T, Cortelli P, Gibbons CH, Goldstein DS, Hainsworth R, Hilz MJ, Jacob G, Kaufmann H, Jordan J, Lipsitz LA, Levine BD, Low PA, Mathias C, Raj SR, Robertson D, Sandroni P, Schatz I, Schondorff R, Stewart JM, van Dijk JG. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res. 2011 Apr;21(2):69-72. doi: 10.1007/s10286-011-0119-5. No abstract available.
PMID: 21431947
citation: Lambert E, Lambert GW. Sympathetic dysfunction in vasovagal syncope and the postural orthostatic tachycardia syndrome. Front Physiol. 2014 Jul 28;5:280. doi: 10.3389/fphys.2014.00280. eCollection 2014.
PMID: 25120493
citation: Ocon AJ, Messer ZR, Medow MS, Stewart JM. Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome. Clin Sci (Lond). 2012 Mar;122(5):227-38. doi: 10.1042/CS20110241.
PMID: 21919887
citation: Raj SR. Postural tachycardia syndrome (POTS). Circulation. 2013 Jun 11;127(23):2336-42. doi: 10.1161/CIRCULATIONAHA.112.144501. No abstract available.
PMID: 23753844
citation: Z'Graggen WJ, Hess CW, Humm AM. Acute fluid ingestion in the treatment of orthostatic intolerance - important implications for daily practice. Eur J Neurol. 2010 Nov;17(11):1370-6. doi: 10.1111/j.1468-1331.2010.03030.x.
PMID: 20412295
responsible party type: Sponsor
mesh term: Postural Orthostatic Tachycardia Syndrome
mesh term: Tachycardia
mesh term: Syndrome
sharing ipd: No