<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/NCT01691976</url>
  </required_header>
  <id_info>
    <org_study_id>CRO2017</org_study_id>
    <nct_id>NCT01691976</nct_id>
  </id_info>
  <brief_title>Mild Cognitive Impairment in Men Following Androgen Deprivation</brief_title>
  <official_title>Mild Cognitive Impairment in Men Following Androgen Deprivation Therapy for Prostate Cancer: a Longitudinal fMRI and qEEG Pilot Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Imperial College London</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      MCI with ageing is thought in part to be related to reduced serum sex hormones which is&#xD;
      well-recognised, especially in females, but poorly understood. International studies&#xD;
      assessing hormone replacement therapy (HRT) to prevent/reduce MCI are ongoing. MCI leads to&#xD;
      morbidity, reduced quality of life and substantial healthcare costs. The commonest&#xD;
      therapeutically induced reduction in sex hormone level in men is treatment of prostate cancer&#xD;
      (PCa). PCa is androgen dependent and androgen-deprivation therapy (ADT) suppressing&#xD;
      testosterone to castrate levels is key therapy for advanced disease. About one million men&#xD;
      worldwide have received ADT for PCa, mostly using luteinising hormone releasing-hormone&#xD;
      agonists (LHRHa) although oral oestrogens were used in the past; eventually perhaps 4% of&#xD;
      Caucasians may be castrated. MCI as a side-effect of castration in men remains poorly&#xD;
      researched. This pilot study will quantify the extent of MCI in men receiving ADT with LHRHa&#xD;
      and oestrogen to inform the design of a larger study to understand mechanisms, predict&#xD;
      affected patients and determine ways of reducing MCI. Researching relationships of sex&#xD;
      hormones and MCI should improve understanding and interventions for slowing/preventing MCI in&#xD;
      PCa survivors. HRT in women slows MCI. Alternatives for ADT include parenteral oestrogen. The&#xD;
      PATCH clinical trial comparing transdermal oestrogen with LHRHa offers an opportunity to&#xD;
      assess oestrogen as preventative for male MCI. Functional magnetic resonance imaging (fMRI),&#xD;
      quantitative electroencephalography (qEEG) and neuropsychological tests will be used to test&#xD;
      this hypothesis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Changes in cognitive function related to altered serum sex hormone levels are well-recognised&#xD;
      but poorly understood. Mild cognitive impairment (MCI) with aging is thought in part to be&#xD;
      related to reduction in serum androgen level and international studies are on-going to&#xD;
      prevent age-related MCI using androgen replacement therapy. Reduction in cognitive function&#xD;
      often leads to morbidity and reduction in quality of life. The commonest therapeutically&#xD;
      induced reduction in sex hormone level in men is in the treatment of prostate cancer. As&#xD;
      prostate cancer is androgen dependent for growth, androgen-deprivation therapy (ADT) to&#xD;
      suppress serum testosterone level to castration levels (&lt; 1.7mM) is the key therapeutic&#xD;
      intervention for advanced disease. Up to 1 million men worldwide are estimated to have been&#xD;
      prescribed ADT for prostate cancer, mostly using luteinising hormone releasing hormone&#xD;
      agonists (LHRHa). ADT is now also used to treat some early prostate cancer and as early&#xD;
      asymptomatic prostate cancer is increasingly being diagnosed and treated following screening&#xD;
      with serum PSA measurement, estimates suggest that eventually up to 4% of all Caucasians will&#xD;
      be castrated.&#xD;
&#xD;
      MCI is a recognized side effect of ADT but little work has been done to quantify the effect,&#xD;
      understand the mechanism, predict which patients will be affected and determine ways of&#xD;
      reducing this side effect. Researching relationships of sex hormones and MCI should improve&#xD;
      understanding and interventions for slowing/preventing MCI in PCa survivors. Hormone&#xD;
      replacement therapy (HRT) in women slows the development of MCI. Alternatives for ADT include&#xD;
      parenteral oestrogens. The PATCH clinical trial comparing transdermal oestrogen with LHRHa&#xD;
      offers an opportunity to assess oestrogen as preventative for male MCI. Functional magnetic&#xD;
      resonance imaging (fMRI), quantitative electroencephalography (qEEG) and neuropsychological&#xD;
      tests will be used to test this hypothesis. Insight into the effect of changes in serum sex&#xD;
      hormones on MCI may provide a guide to improving MCI in aging and improve the quality of life&#xD;
      of prostate cancer survivors.&#xD;
&#xD;
      This study aims to (i) measure cognitive changes in prostate cancer patients receiving ADT&#xD;
      with either LHRHa or transdermal oestrogen and (ii) relate MCI to changes in serum hormone&#xD;
      levels. Simultaneous high-resolution fMRI of the brain and 64-channel qEEG will be used for&#xD;
      the first time in this patient group. MCI will be investigated by assessing changes in&#xD;
      parietal lobe activation to mental rotation tasks and changes in global resting-state fMRI&#xD;
      and qEEG activity and comparisons will be made with the cognitive assessment carried out by&#xD;
      neuropsychological tests.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No one recruited due to resource limitations. Issues with how complicated the study could be&#xD;
    for patients so the study was later modified and turned into a different study.&#xD;
  </why_stopped>
  <start_date type="Actual">October 2012</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">December 2013</primary_completion_date>
  <phase>N/A</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>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective evaluation of mild cognitive impairment on parietal fMRI signals</measure>
    <time_frame>6 months</time_frame>
    <description>The primary outcome measure is the development of MCI following ADT with LHRHa, as evaluated by fMRI. The group change in the parietal blood oxygen level-dependent echoplanar imaging (BOLD EPI) fMRI signal associated with a three-dimensional rotation cognitive activation task at six-month follow-up compared with baseline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective evaluation of mild cognitive impairment on non-parietal fMRI signals</measure>
    <time_frame>6 months</time_frame>
    <description>One of the secondary outcome measures is the development of MCI following ADT with LHRHa, as evaluated by the group change in non-parietal BOLD EPI fMRI signals associated with the three-dimensional rotation cognitive activation task at six-month follow-up compared with baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Electroencephalographic evaluation of mild cognitive impairment</measure>
    <time_frame>6 months</time_frame>
    <description>One of the secondary outcome measures is the development of MCI following ADT with LHRHa, as evaluated by the electroencephalographic frequency changes associated with the three-dimensional rotation cognitive activation task at six-month follow-up compared with baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjective evaluation of mild cognitive impairment by CANTAB</measure>
    <time_frame>6 months</time_frame>
    <description>One of the secondary outcome measures is the development of MCI following ADT with LHRHa, as evaluated by CANTAB changes associated with the three-dimensional rotation cognitive activation task at six-month follow-up compared with baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjective evaluation of mild cognitive impairment by ADAS-cog</measure>
    <time_frame>6 months</time_frame>
    <description>One of the secondary outcome measures is the development of MCI following ADT with LHRHa, as evaluated by ADAS-cog changes associated with the three-dimensional rotation cognitive activation task at six-month follow-up compared with baseline.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Serum testosterone levels</measure>
    <time_frame>6 months</time_frame>
    <description>Measurement of change in serum testosterone levels at baseline and after six months of ADT with LHRHa.</description>
  </other_outcome>
  <other_outcome>
    <measure>Serum oestradiol levels</measure>
    <time_frame>6 months</time_frame>
    <description>Measurement of change in serum oestradiol levels at baseline and after six months of ADT with LHRHa.</description>
  </other_outcome>
  <other_outcome>
    <measure>Serum luteinising hormone levels</measure>
    <time_frame>6 months</time_frame>
    <description>Measurement of change in serum luteinising hormone levels at baseline and after six months of ADT with LHRHa.</description>
  </other_outcome>
  <other_outcome>
    <measure>Serum follicle-stimulating hormone levels</measure>
    <time_frame>6 months</time_frame>
    <description>Measurement of change in serum follicle stimulating hormone levels at baseline and after six months of ADT with LHRHa.</description>
  </other_outcome>
  <other_outcome>
    <measure>Serum albumin</measure>
    <time_frame>6 months</time_frame>
    <description>Measurement of change in serum albumin concentration at baseline and after six months of ADT with LHRHa.</description>
  </other_outcome>
  <other_outcome>
    <measure>Serum sex hormone binding globulin</measure>
    <time_frame>6 months</time_frame>
    <description>Measurement of change in serum sex hormone binding globulin concentration at baseline and after six months of ADT with LHRHa.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Controls</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Age-matched male patients with benign prostatic hyperplasia, otherwise healthy, as controls</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LHRHa</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Prostate cancer patients receiving androgen deprivation therapy by luteinising hormone releasing-hormone agonists (LHRHa)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Oestrogen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Prostate cancer patients recruited from the Prostate Adenocarcinoma TransCutaneous Hormones (PATCH) Trial, randomised to receive ADT via transdermal oestrogen patches.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oestrogen Patches</intervention_name>
    <arm_group_label>Oestrogen</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LHRHa</intervention_name>
    <description>Luteinising hormone releasing-hormone agonists (LHRHa)</description>
    <arm_group_label>LHRHa</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male patients between the ages 50 to 90 years beginning ADT with LHRHa or PATCH&#xD;
             participants randomised to either LHRHa or transdermal oestrogen for either newly&#xD;
             diagnosed advanced prostate cancer or previously treated with radical radiotherapy or&#xD;
             surgery and now having a rising prostate specific antigen will be included in the&#xD;
             study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with a known history of dementia will be excluded as well as those patients&#xD;
             who have received any prior hormone therapy for localised prostate cancer.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paul D Abel, ChM, FRCS</last_name>
    <role>Study Chair</role>
    <affiliation>Imperial College London and Imperial College Healthcare NHS Trust</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Syed IA Shah, MBBS, MPhil</last_name>
    <role>Principal Investigator</role>
    <affiliation>Imperial College London and Imperial College Healthcare NHS Trust</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Adam Waldman</last_name>
    <role>Principal Investigator</role>
    <affiliation>Imperial College Healthcare NHS Trust</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Basant K Puri</last_name>
    <role>Principal Investigator</role>
    <affiliation>Imperial College Healthcare NHS Trust</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Pat Price</last_name>
    <role>Principal Investigator</role>
    <affiliation>Imperial College London</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Imperial College Healthcare NHS Trust</name>
      <address>
        <city>London</city>
        <zip>W12 0NN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>September 11, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2012</study_first_posted>
  <last_update_submitted>November 18, 2020</last_update_submitted>
  <last_update_submitted_qc>November 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 20, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Mild cognitive impairment</keyword>
  <keyword>Androgen deprivation therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Estrogens</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01691976
org study id: CRO2017
nct id: NCT01691976
lead sponsor: 
has dmc: No
MCI with ageing is thought in part to be related to reduced serum sex hormones which is
      well-recognised, especially in females, but poorly understood. International studies
      assessing hormone replacement therapy (HRT) to prevent/reduce MCI are ongoing. MCI leads to
      morbidity, reduced quality of life and substantial healthcare costs. The commonest
      therapeutically induced reduction in sex hormone level in men is treatment of prostate cancer
      (PCa). PCa is androgen dependent and androgen-deprivation therapy (ADT) suppressing
      testosterone to castrate levels is key therapy for advanced disease. About one million men
      worldwide have received ADT for PCa, mostly using luteinising hormone releasing-hormone
      agonists (LHRHa) although oral oestrogens were used in the past; eventually perhaps 4% of
      Caucasians may be castrated. MCI as a side-effect of castration in men remains poorly
      researched. This pilot study will quantify the extent of MCI in men receiving ADT with LHRHa
      and oestrogen to inform the design of a larger study to understand mechanisms, predict
      affected patients and determine ways of reducing MCI. Researching relationships of sex
      hormones and MCI should improve understanding and interventions for slowing/preventing MCI in
      PCa survivors. HRT in women slows MCI. Alternatives for ADT include parenteral oestrogen. The
      PATCH clinical trial comparing transdermal oestrogen with LHRHa offers an opportunity to
      assess oestrogen as preventative for male MCI. Functional magnetic resonance imaging (fMRI),
      quantitative electroencephalography (qEEG) and neuropsychological tests will be used to test
      this hypothesis.
Changes in cognitive function related to altered serum sex hormone levels are well-recognised
      but poorly understood. Mild cognitive impairment (MCI) with aging is thought in part to be
      related to reduction in serum androgen level and international studies are on-going to
      prevent age-related MCI using androgen replacement therapy. Reduction in cognitive function
      often leads to morbidity and reduction in quality of life. The commonest therapeutically
      induced reduction in sex hormone level in men is in the treatment of prostate cancer. As
      prostate cancer is androgen dependent for growth, androgen-deprivation therapy (ADT) to
      suppress serum testosterone level to castration levels (< 1.7mM) is the key therapeutic
      intervention for advanced disease. Up to 1 million men worldwide are estimated to have been
      prescribed ADT for prostate cancer, mostly using luteinising hormone releasing hormone
      agonists (LHRHa). ADT is now also used to treat some early prostate cancer and as early
      asymptomatic prostate cancer is increasingly being diagnosed and treated following screening
      with serum PSA measurement, estimates suggest that eventually up to 4% of all Caucasians will
      be castrated.

      MCI is a recognized side effect of ADT but little work has been done to quantify the effect,
      understand the mechanism, predict which patients will be affected and determine ways of
      reducing this side effect. Researching relationships of sex hormones and MCI should improve
      understanding and interventions for slowing/preventing MCI in PCa survivors. Hormone
      replacement therapy (HRT) in women slows the development of MCI. Alternatives for ADT include
      parenteral oestrogens. The PATCH clinical trial comparing transdermal oestrogen with LHRHa
      offers an opportunity to assess oestrogen as preventative for male MCI. Functional magnetic
      resonance imaging (fMRI), quantitative electroencephalography (qEEG) and neuropsychological
      tests will be used to test this hypothesis. Insight into the effect of changes in serum sex
      hormones on MCI may provide a guide to improving MCI in aging and improve the quality of life
      of prostate cancer survivors.

      This study aims to (i) measure cognitive changes in prostate cancer patients receiving ADT
      with either LHRHa or transdermal oestrogen and (ii) relate MCI to changes in serum hormone
      levels. Simultaneous high-resolution fMRI of the brain and 64-channel qEEG will be used for
      the first time in this patient group. MCI will be investigated by assessing changes in
      parietal lobe activation to mental rotation tasks and changes in global resting-state fMRI
      and qEEG activity and comparisons will be made with the cognitive assessment carried out by
      neuropsychological tests.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Objective evaluation of mild cognitive impairment on parietal fMRI signals
time frame: 6 months
description: The primary outcome measure is the development of MCI following ADT with LHRHa, as evaluated by fMRI. The group change in the parietal blood oxygen level-dependent echoplanar imaging (BOLD EPI) fMRI signal associated with a three-dimensional rotation cognitive activation task at six-month follow-up compared with baseline.
measure: Objective evaluation of mild cognitive impairment on non-parietal fMRI signals
time frame: 6 months
description: One of the secondary outcome measures is the development of MCI following ADT with LHRHa, as evaluated by the group change in non-parietal BOLD EPI fMRI signals associated with the three-dimensional rotation cognitive activation task at six-month follow-up compared with baseline.
measure: Electroencephalographic evaluation of mild cognitive impairment
time frame: 6 months
description: One of the secondary outcome measures is the development of MCI following ADT with LHRHa, as evaluated by the electroencephalographic frequency changes associated with the three-dimensional rotation cognitive activation task at six-month follow-up compared with baseline.
measure: Subjective evaluation of mild cognitive impairment by CANTAB
time frame: 6 months
description: One of the secondary outcome measures is the development of MCI following ADT with LHRHa, as evaluated by CANTAB changes associated with the three-dimensional rotation cognitive activation task at six-month follow-up compared with baseline.
measure: Subjective evaluation of mild cognitive impairment by ADAS-cog
time frame: 6 months
description: One of the secondary outcome measures is the development of MCI following ADT with LHRHa, as evaluated by ADAS-cog changes associated with the three-dimensional rotation cognitive activation task at six-month follow-up compared with baseline.
measure: Serum testosterone levels
time frame: 6 months
description: Measurement of change in serum testosterone levels at baseline and after six months of ADT with LHRHa.
measure: Serum oestradiol levels
time frame: 6 months
description: Measurement of change in serum oestradiol levels at baseline and after six months of ADT with LHRHa.
measure: Serum luteinising hormone levels
time frame: 6 months
description: Measurement of change in serum luteinising hormone levels at baseline and after six months of ADT with LHRHa.
measure: Serum follicle-stimulating hormone levels
time frame: 6 months
description: Measurement of change in serum follicle stimulating hormone levels at baseline and after six months of ADT with LHRHa.
measure: Serum albumin
time frame: 6 months
description: Measurement of change in serum albumin concentration at baseline and after six months of ADT with LHRHa.
measure: Serum sex hormone binding globulin
time frame: 6 months
description: Measurement of change in serum sex hormone binding globulin concentration at baseline and after six months of ADT with LHRHa.
arm group label: Controls
arm group type: No Intervention
description: Age-matched male patients with benign prostatic hyperplasia, otherwise healthy, as controls
arm group label: LHRHa
arm group type: Active Comparator
description: Prostate cancer patients receiving androgen deprivation therapy by luteinising hormone releasing-hormone agonists (LHRHa)
arm group label: Oestrogen
arm group type: Experimental
description: Prostate cancer patients recruited from the Prostate Adenocarcinoma TransCutaneous Hormones (PATCH) Trial, randomised to receive ADT via transdermal oestrogen patches.
intervention type: Drug
intervention name: Oestrogen Patches
arm group label: Oestrogen
intervention type: Drug
intervention name: LHRHa
description: Luteinising hormone releasing-hormone agonists (LHRHa)
arm group label: LHRHa
criteria: 
gender: Male
minimum age: 50 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Paul D Abel, ChM, FRCS
role: Study Chair
affiliation: Imperial College London and Imperial College Healthcare NHS Trust
last name: Syed IA Shah, MBBS, MPhil
role: Principal Investigator
affiliation: Imperial College London and Imperial College Healthcare NHS Trust
last name: Adam Waldman
role: Principal Investigator
affiliation: Imperial College Healthcare NHS Trust
last name: Basant K Puri
role: Principal Investigator
affiliation: Imperial College Healthcare NHS Trust
last name: Pat Price
role: Principal Investigator
affiliation: Imperial College London
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Cognitive Dysfunction
mesh term: Estrogens