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/NCT05990491</url>
    </required_header>
    <id_info>
      <org_study_id>A-05-PGI/IMP/87/2023</org_study_id>
      <nct_id>NCT05990491</nct_id>
    </id_info>
    <brief_title>Pituitary Function After Recovery From Septic Shock Among ICU Survivors</brief_title>
    <official_title>Pituitary Function After Recovery From Septic Shock Among ICU Survivors: A Prospective, Observational Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sanjay Gandhi Postgraduate Institute of Medical Sciences</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Sanjay Gandhi Postgraduate Institute of Medical Sciences</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>
        Prolonged circulatory shock is associated with marked disturbances in vascular supply to the&#xD;
        brain, and endothelial dysfunction which can lead to disseminated intravascular coagulation&#xD;
        and microvascular thrombosis. Pituitary dysfunction is documented following post-partum&#xD;
        hemorrhage, traumatic brain injury and subarachnoid hemorrhage, which also affect blood flow&#xD;
        to the pituitary. However, there are no studies assessing pituitary function in the aftermath&#xD;
        of recovery from shock. This will be a prospective observational study of patients admitted&#xD;
        in Critical Care Medicine (CCM) ICU who have recovered from prolonged septic shock (Lasting&#xD;
        for a period of &gt; 24 hours). Blood samples of the participants will be estimated at the time&#xD;
        of discharge from the ICU and at 6 months post discharge. Investigators will estimate fasting&#xD;
        serum cortisol, TSH, Free T4, Testosterone (in males), Oestrogen (in females), LH, FSH,&#xD;
        Prolactin, IGF-1 and plasma ACTH in all participants at both time points (at the time of ICU&#xD;
        discharge and at 6-months follow-up). Participants who have borderline serum cortisol values&#xD;
        (138-400 nmol/l) will be subjected to 250ug ACTH stimulation test. Expected outcome of the&#xD;
        proposed study is to know proportion of patients having pituitary hormone axis dysfunction.&#xD;
        Investigators will also look for pituitary dysfunction persist or revert, or there are new&#xD;
        onset dysfunction at 6 month follow up. This would have major implications in the follow up&#xD;
        and management of ICU survivors.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The pituitary gland receives its arterial blood supply from the superior and inferior&#xD;
        hypophyseal arteries, which arise from the internal carotid artery. The infundibulum, the&#xD;
        median eminence and the pars tuberalis are supplied by the superior hypophyseal artery and&#xD;
        the posterior lobe by the inferior hypophyseal artery. By contrast, the pars distalis&#xD;
        (anterior pituitary) is mainly supplied by the venous system. The long portal system, arising&#xD;
        from the capillary plexus around the median eminence, and the short portal system arising&#xD;
        from the posterior pituitary account for 70% and 30% respectively, of the total blood supply&#xD;
        to the anterior pituitary gland. This unique circulation allows the pars distalis to receive&#xD;
        humoral signals from the hypothalamus and the posterior pituitary; however, it renders the&#xD;
        pituitary susceptible to ischemia due to hypotension, hypovolemia and vascular thrombosis.&#xD;
  &#xD;
        The prototype illness where pituitary necrosis leads to pituitary dysfunction is post-partum&#xD;
        pituitary necrosis (Sheehan syndrome). The pituitary gland becomes vulnerable to changes in&#xD;
        blood flow during and shortly after pregnancy owing to the increased size of the gland,&#xD;
        leading to both increased demand and compression of the vasculature of the gland. In&#xD;
        addition, pregnancy is a thrombophilic state which increases risk for intravascular&#xD;
        thrombosis. Hypotension secondary to post-partum hemorrhage causes pituitary necrosis and&#xD;
        leads to hypopituitarism. Vascular insults to the pituitary are also implicated in other&#xD;
        forms of pituitary damage, such as following traumatic brain injury, following snakebite&#xD;
        envenomation, subarachnoid hemorrhage and hemorrhagic shock.&#xD;
  &#xD;
        Circulatory shock replicates many of the pathophysiological processes described above.&#xD;
        Clinical classifications of shock include hypovolemic, cardiogenic, distributive (septic),&#xD;
        and obstructive types. While the pathophysiology of each type of shock is different and&#xD;
        complex, the final common pathway is poor perfusion, anaerobic metabolism, lactic acidosis,&#xD;
        and release of inflammatory mediators with resultant tissue damage. Sepsis and septic shock&#xD;
        are often complicated by Disseminated Intravascular Coagulation (DIC) which leads to&#xD;
        widespread microvascular thrombosis. Hypotension leads to reduced blood flow to the&#xD;
        hypothalamo-pituitary unit and all these factors may lead on to ischemia and infarction of&#xD;
        the hypothalamo-pituitary unit. Patients who recovered post cardiac arrest suffer an extreme&#xD;
        form of this insult where blood flow to the brain is almost entirely cut off for a period of&#xD;
        time, followed by reperfusion.&#xD;
  &#xD;
        Post ICU Care Syndrome (PICS) is estimated to occur in 30-80% of patients post discharge from&#xD;
        the intensive care unit. Many of the manifestations of Post ICU Care Syndrome (PICS), such as&#xD;
        fatigue, cognitive dysfunction, neuromuscular weakness, amenorrhea and sexual dysfunction&#xD;
        overlap with those seen in hypopituitarism. However, there is no literature describing the&#xD;
        role of pituitary dysfunction in these patients.&#xD;
  &#xD;
        Based on the above evidence, we hypothesize that patients who recover from severe shock may&#xD;
        have hypothalamic-pituitary damage leading to hypopituitarism. Due to the current lack of&#xD;
        literature on this topic, we propose to study pituitary function in ICU survivors who&#xD;
        recovered from the septic shock.&#xD;
  &#xD;
        The primary objective is to study the prevalence of dysfunction of various pituitary hormone&#xD;
        axes at the time of ICU discharge in participants who recovered from the septic shock. The&#xD;
        secondary objective is to look for the recovery of pituitary function or new onset pituitary&#xD;
        dysfunction at 6 months post-discharge from the ICU, in these included participants.&#xD;
  &#xD;
        This will be a prospective, observational study of participants undergoing treatment for&#xD;
        septic shock in the Department of Critical Care Medicine (CCM), SGPGIMS, Lucknow.&#xD;
  &#xD;
        Details of premorbid conditions, precipitating illness, clinical parameters and treatments&#xD;
        provided to the participants will be recorded. Levels of pituitary hormones [Cortisol (Basal&#xD;
        and stimulated), ACTH, IGF-1, LH, FSH, Testosterone (in males), Estradiol (in females),&#xD;
        Prolactin, TSH and free T4] will be assessed in fasting state, prior to discharge from the&#xD;
        ICU. Participants will be interviewed telephonically at 3 months post-discharge to assess&#xD;
        quality of life using the SF-36 questionnaire and for symptoms suggestive of hypopituitarism.&#xD;
        At 6 months post-discharge, the various pituitary hormone levels [Cortisol (Basal and&#xD;
        stimulated), ACTH, IGF-1, LH, FSH, Testosterone (in males), Estradiol (in females),&#xD;
        Prolactin, TSH and free T4] will be assessed again along with assessment of quality of life&#xD;
        using SF-36. Any pituitary hormone deficiency identified on testing will be evaluated and&#xD;
        managed as per standard practice.&#xD;
  &#xD;
        Investigators aim to include 90 participants in the study. Continuous variables will be&#xD;
        presented in mean and standard deviation (SD) or median (interquartile range) depending upon&#xD;
        normality status. Independent samples t test (for independent groups) / Paired t test (paired&#xD;
        groups) or their non-parametric counterparts will be used to compare the means or medians&#xD;
        between the groups, respectively. Categorical variables will be presented in number (%) and&#xD;
        will be compared by Chi square test / Fisher exact test, as appropriate. One-way Repeated&#xD;
        Measures ANOVA or Friedman test will be used to compare the means or medians over the time as&#xD;
        appropriate. Binary logistic regression analysis will be used to assess the factors&#xD;
        associated with pituitary dysfunction among the study participants.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 28, 2023</start_date>
    <completion_date type="Anticipated">August 2025</completion_date>
    <primary_completion_date type="Anticipated">August 2025</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Pituitary dysfunction at discharge</measure>
      <time_frame>Immediately before the ICU discharge</time_frame>
      <description>Frequency of dysfunction of various hypothalamo-pituitary hormone axes</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Pituitary dysfunction at 6 months</measure>
      <time_frame>Six months after the ICU discharge</time_frame>
      <description>Frequency of dysfunction of various hypothalamo-pituitary hormone axes on follow up</description>
    </secondary_outcome>
    <enrollment type="Anticipated">90</enrollment>
    <condition>Shock, Septic</condition>
    <condition>Pituitary Dysfunction</condition>
    <condition>Hypopituitarism</condition>
    <biospec_retention>Samples With DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        Blood samples (8-10 ml) collected at the time of recruitment and at 6 months follow-up.&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          Consecutive patients admitted to critical care medicine intensive care unit at Sanjay&#xD;
          Gandhi Postgraduate Institute of Medical Sciences, Lucknow who meet the inclusion and&#xD;
          exclusion criteria&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients 18-80 years of age who meet the definition of septic shock.&#xD;
  &#xD;
            -  Vasopressor requirement should be maintained for a period &gt; 24 hours and should&#xD;
               require ICU stay for a duration of &gt; 7 days.&#xD;
  &#xD;
            -  Patient should recover from shock and be planned for discharge from the ICU.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients who refuse to provide consent.&#xD;
  &#xD;
            -  Age &lt;18 years or &gt; 80 years of age.&#xD;
  &#xD;
            -  Pregnancy or immediate post-partum (&lt; 6 months post-delivery).&#xD;
  &#xD;
            -  Chronic kidney disease (Stage 5), chronic liver disease (CHILD B or C), severe Chronic&#xD;
               obstructive pulmonary disease, Chronic heart failure.&#xD;
  &#xD;
            -  Patients with pre-existing hypopituitarism on replacement.&#xD;
  &#xD;
            -  Past history of severe post-partum hemorrhage requiring blood transfusion, traumatic&#xD;
               brain injury, subarachnoid hemorrhage, pituitary tumor/surgery, snake bite&#xD;
               envenomation and meningo-encephalitis.&#xD;
  &#xD;
            -  Patients who have been on &gt; 5 mg prednisolone equivalent for a period of more than 2&#xD;
               weeks at any time in the previous 6 months before admission.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Subhash Yadav</last_name>
      <role>Principal Investigator</role>
      <affiliation>Sanjay Gandhi Postgraduate Institute of Medical Sciences</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Mohan Gurjar</last_name>
      <role>Principal Investigator</role>
      <affiliation>Sanjay Gandhi Postgraduate Institute of Medical Sciences</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Jayakrishnan C, DM</last_name>
      <role>Principal Investigator</role>
      <affiliation>Sanjay Gandhi Postgraduate Institute of Medical Sciences</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Harilal K, MD</last_name>
      <phone>+91-8089728532</phone>
      <email>hari2012686@gmail.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Jayakrishnan C, DM</last_name>
      <phone>+91-8281868653</phone>
      <email>jake3129@gmail.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Department of Critical Care Medicine, SGPGIMS</name>
        <address>
          <city>Lucknow</city>
          <state>UP</state>
          <zip>226014</zip>
          <country>India</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Mohan Gurjar, MD, PDCC</last_name>
        <phone>915222495403</phone>
        <email>m.gurjar@rediffmail.com</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Department of Endocrinology, SGPGIMS</name>
        <address>
          <city>Lucknow</city>
          <state>Uttar Pradesh</state>
          <zip>226014</zip>
          <country>India</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Harilal K, MD</last_name>
        <phone>+91-8089728532</phone>
        <email>hari2012686@gmail.com</email>
      </contact>
      <contact_backup>
        <last_name>Jayakrishnan C, DM</last_name>
        <phone>+91-8281868653</phone>
        <email>jake3129@gmail.com</email>
      </contact_backup>
      <investigator>
        <last_name>Subhash Yadav, MD, DM</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>India</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 30, 2023</study_first_submitted>
    <study_first_submitted_qc>August 5, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 28, 2023</last_update_submitted>
    <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 29, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Sanjay Gandhi Postgraduate Institute of Medical Sciences</investigator_affiliation>
      <investigator_full_name>Mohan Gurjar</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <keyword>Septic shock</keyword>
    <keyword>Post intensive care syndrome</keyword>
    <keyword>Hypopituitarism</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Shock, Septic</mesh_term>
      <mesh_term>Pituitary Diseases</mesh_term>
      <mesh_term>Hypopituitarism</mesh_term>
      <mesh_term>Shock</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/NCT05990491
  org study id: A-05-PGI/IMP/87/2023
  nct id: NCT05990491
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Prolonged circulatory shock is associated with marked disturbances in vascular supply to the
        brain, and endothelial dysfunction which can lead to disseminated intravascular coagulation
        and microvascular thrombosis. Pituitary dysfunction is documented following post-partum
        hemorrhage, traumatic brain injury and subarachnoid hemorrhage, which also affect blood flow
        to the pituitary. However, there are no studies assessing pituitary function in the aftermath
        of recovery from shock. This will be a prospective observational study of patients admitted
        in Critical Care Medicine (CCM) ICU who have recovered from prolonged septic shock (Lasting
        for a period of > 24 hours). Blood samples of the participants will be estimated at the time
        of discharge from the ICU and at 6 months post discharge. Investigators will estimate fasting
        serum cortisol, TSH, Free T4, Testosterone (in males), Oestrogen (in females), LH, FSH,
        Prolactin, IGF-1 and plasma ACTH in all participants at both time points (at the time of ICU
        discharge and at 6-months follow-up). Participants who have borderline serum cortisol values
        (138-400 nmol/l) will be subjected to 250ug ACTH stimulation test. Expected outcome of the
        proposed study is to know proportion of patients having pituitary hormone axis dysfunction.
        Investigators will also look for pituitary dysfunction persist or revert, or there are new
        onset dysfunction at 6 month follow up. This would have major implications in the follow up
        and management of ICU survivors.
  The pituitary gland receives its arterial blood supply from the superior and inferior
        hypophyseal arteries, which arise from the internal carotid artery. The infundibulum, the
        median eminence and the pars tuberalis are supplied by the superior hypophyseal artery and
        the posterior lobe by the inferior hypophyseal artery. By contrast, the pars distalis
        (anterior pituitary) is mainly supplied by the venous system. The long portal system, arising
        from the capillary plexus around the median eminence, and the short portal system arising
        from the posterior pituitary account for 70% and 30% respectively, of the total blood supply
        to the anterior pituitary gland. This unique circulation allows the pars distalis to receive
        humoral signals from the hypothalamus and the posterior pituitary; however, it renders the
        pituitary susceptible to ischemia due to hypotension, hypovolemia and vascular thrombosis.
  
        The prototype illness where pituitary necrosis leads to pituitary dysfunction is post-partum
        pituitary necrosis (Sheehan syndrome). The pituitary gland becomes vulnerable to changes in
        blood flow during and shortly after pregnancy owing to the increased size of the gland,
        leading to both increased demand and compression of the vasculature of the gland. In
        addition, pregnancy is a thrombophilic state which increases risk for intravascular
        thrombosis. Hypotension secondary to post-partum hemorrhage causes pituitary necrosis and
        leads to hypopituitarism. Vascular insults to the pituitary are also implicated in other
        forms of pituitary damage, such as following traumatic brain injury, following snakebite
        envenomation, subarachnoid hemorrhage and hemorrhagic shock.
  
        Circulatory shock replicates many of the pathophysiological processes described above.
        Clinical classifications of shock include hypovolemic, cardiogenic, distributive (septic),
        and obstructive types. While the pathophysiology of each type of shock is different and
        complex, the final common pathway is poor perfusion, anaerobic metabolism, lactic acidosis,
        and release of inflammatory mediators with resultant tissue damage. Sepsis and septic shock
        are often complicated by Disseminated Intravascular Coagulation (DIC) which leads to
        widespread microvascular thrombosis. Hypotension leads to reduced blood flow to the
        hypothalamo-pituitary unit and all these factors may lead on to ischemia and infarction of
        the hypothalamo-pituitary unit. Patients who recovered post cardiac arrest suffer an extreme
        form of this insult where blood flow to the brain is almost entirely cut off for a period of
        time, followed by reperfusion.
  
        Post ICU Care Syndrome (PICS) is estimated to occur in 30-80% of patients post discharge from
        the intensive care unit. Many of the manifestations of Post ICU Care Syndrome (PICS), such as
        fatigue, cognitive dysfunction, neuromuscular weakness, amenorrhea and sexual dysfunction
        overlap with those seen in hypopituitarism. However, there is no literature describing the
        role of pituitary dysfunction in these patients.
  
        Based on the above evidence, we hypothesize that patients who recover from severe shock may
        have hypothalamic-pituitary damage leading to hypopituitarism. Due to the current lack of
        literature on this topic, we propose to study pituitary function in ICU survivors who
        recovered from the septic shock.
  
        The primary objective is to study the prevalence of dysfunction of various pituitary hormone
        axes at the time of ICU discharge in participants who recovered from the septic shock. The
        secondary objective is to look for the recovery of pituitary function or new onset pituitary
        dysfunction at 6 months post-discharge from the ICU, in these included participants.
  
        This will be a prospective, observational study of participants undergoing treatment for
        septic shock in the Department of Critical Care Medicine (CCM), SGPGIMS, Lucknow.
  
        Details of premorbid conditions, precipitating illness, clinical parameters and treatments
        provided to the participants will be recorded. Levels of pituitary hormones [Cortisol (Basal
        and stimulated), ACTH, IGF-1, LH, FSH, Testosterone (in males), Estradiol (in females),
        Prolactin, TSH and free T4] will be assessed in fasting state, prior to discharge from the
        ICU. Participants will be interviewed telephonically at 3 months post-discharge to assess
        quality of life using the SF-36 questionnaire and for symptoms suggestive of hypopituitarism.
        At 6 months post-discharge, the various pituitary hormone levels [Cortisol (Basal and
        stimulated), ACTH, IGF-1, LH, FSH, Testosterone (in males), Estradiol (in females),
        Prolactin, TSH and free T4] will be assessed again along with assessment of quality of life
        using SF-36. Any pituitary hormone deficiency identified on testing will be evaluated and
        managed as per standard practice.
  
        Investigators aim to include 90 participants in the study. Continuous variables will be
        presented in mean and standard deviation (SD) or median (interquartile range) depending upon
        normality status. Independent samples t test (for independent groups) / Paired t test (paired
        groups) or their non-parametric counterparts will be used to compare the means or medians
        between the groups, respectively. Categorical variables will be presented in number (%) and
        will be compared by Chi square test / Fisher exact test, as appropriate. One-way Repeated
        Measures ANOVA or Friedman test will be used to compare the means or medians over the time as
        appropriate. Binary logistic regression analysis will be used to assess the factors
        associated with pituitary dysfunction among the study participants.
  observational model: Cohort
  time perspective: Prospective
  measure: Pituitary dysfunction at discharge
  time frame: Immediately before the ICU discharge
  description: Frequency of dysfunction of various hypothalamo-pituitary hormone axes
  measure: Pituitary dysfunction at 6 months
  time frame: Six months after the ICU discharge
  description: Frequency of dysfunction of various hypothalamo-pituitary hormone axes on follow up
  Blood samples (8-10 ml) collected at the time of recruitment and at 6 months follow-up.
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  healthy volunteers: No
  last name: Subhash Yadav
  role: Principal Investigator
  affiliation: Sanjay Gandhi Postgraduate Institute of Medical Sciences
  last name: Mohan Gurjar
  role: Principal Investigator
  affiliation: Sanjay Gandhi Postgraduate Institute of Medical Sciences
  last name: Jayakrishnan C, DM
  role: Principal Investigator
  affiliation: Sanjay Gandhi Postgraduate Institute of Medical Sciences
  last name: Harilal K, MD
  phone: +91-8089728532
  email: hari2012686@gmail.com
  last name: Jayakrishnan C, DM
  phone: +91-8281868653
  email: jake3129@gmail.com
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  country: India
  responsible party type: Principal Investigator
  investigator affiliation: Sanjay Gandhi Postgraduate Institute of Medical Sciences
  investigator full name: Mohan Gurjar
  investigator title: Professor
  mesh term: Shock, Septic
  mesh term: Pituitary Diseases
  mesh term: Hypopituitarism
  mesh term: Shock
  sharing ipd: No