<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/NCT03277222</url>
  </required_header>
  <id_info>
    <org_study_id>REB17-0104</org_study_id>
    <secondary_id>Control# 204512</secondary_id>
    <nct_id>NCT03277222</nct_id>
  </id_info>
  <brief_title>Intranasal Treatment of HIV-associated Neurocognitive Disorders</brief_title>
  <official_title>HAND IN Insulin-001: Intranasal Treatment of HIV-associated Neurocognitive Disorders</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Calgary</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Canadian Institutes of Health Research (CIHR)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Alberta</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Epidemiology Coordinating and Research Centre, Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Calgary</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>
      This study aims to see whether intranasal insulin is an effective treatment for problems with&#xD;
      memory, concentration, slowed thinking, or any other cognitive function in people living with&#xD;
      HIV/AIDS. This group of signs and symptoms are called 'HIV-associated neurocognitive&#xD;
      disorders' or HAND. HAND can affect people living with HIV/AIDS even when they receive potent&#xD;
      anti-HIV treatments. Treatment of HAND by specific medication or other means is not yet&#xD;
      available. Intranasal insulin treatment has virtually no side-effects, and has already been&#xD;
      tested in people with Alzheimer's disease, where it showed beneficial effects on memory, mood&#xD;
      and quality of life&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is designed as a prospective, double-blinded pilot study of intranasal (IN)&#xD;
      insulin versus placebo in people with HAND (n = 20) on stable ART medication. Participants&#xD;
      will be randomly assigned to one of two groups: 40 IU IN insulin R twice daily, or&#xD;
      matched-volume placebo, which will be administered twice daily, taken after breakfast and&#xD;
      again after dinner using a nasal delivery device. Serum glucose will be tested for&#xD;
      hypoglycemia one hour after the initial administration of IN insulin or placebo and after&#xD;
      administration at Weeks 1, 2, and 3. If the dose is tolerated and no side effects are&#xD;
      reported the participant will continue in the study. If the dose is not tolerated due to&#xD;
      hypoglycemia then the participant will be withdrawn from the study.&#xD;
&#xD;
      The objectives of this study are as follows:&#xD;
&#xD;
      Primary: Determine if IN insulin treatment administered twice daily for 4 months reduces&#xD;
      overall neurocognitive deficits (based on the global z-score in people with HAND).&#xD;
&#xD;
      Secondary: Measure effects of IN insulin on individual neuropsychological domains (e.g.,&#xD;
      memory, processing speed, executive functions, motor functions) and on HAND disease&#xD;
      progression; Define impacts of IN insulin on quality of life and mood in people with HAND;&#xD;
      Investigate IN insulin's effects on HAND biomarker profiles in urine and blood.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Unable to find further eligible participants&#xD;
  </why_stopped>
  <start_date type="Actual">November 1, 2018</start_date>
  <completion_date type="Actual">April 21, 2019</completion_date>
  <primary_completion_date type="Actual">April 21, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Arm 1: Drug: IN insulin Dose: Twice daily IN insulin R at 40 IU (n=10) twice daily using a nasal delivery device. IN insulin R will be administered twice daily.&#xD;
Arm 2: Drug: Sterile Saline placebo Dose: Placebo (Sterile Saline placebo, matched volume; (n=10) twice daily using nasal delivery device.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>This is a prospective dose-ranging double-blinded pilot study over 4 months. At enrolment, participants and their physicians will be blinded to treatment.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Global Neurocognitive Performance from Baseline</measure>
    <time_frame>18 weeks</time_frame>
    <description>Change in overall neurocognitive function as measured by the global z score. The global z score is one measurement calculated as the average of z scores from each domain tested.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Neurocognitive Performance: Memory</measure>
    <time_frame>18 weeks</time_frame>
    <description>Change from baseline in the overall z score for the memory domain, calculated as the average of z scores from: Hopkins Verbal Learning Test, Logical Memory Test, and Brief Visual Memory Test (immediate and delayed recall).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Neurocognitive Performance: Executive Function</measure>
    <time_frame>18 weeks</time_frame>
    <description>Change from baseline in the overall z score for the executive function domain, calculated as the average of z scores from: D-KEFS Trail-making Task (Letter-Switching) and Color-Word Interference (Stroop).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Neurocognitive Performance: Attention</measure>
    <time_frame>18 weeks</time_frame>
    <description>Change from baseline in the overall z score for the attention domain, calculated as the average of z scores from: Symbol Digit Modalities Test, D-KEFS Trail-making Test (Number), and Color-Word Interference (Color and Word Reading).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Neurocognitive Performance: Motor Function</measure>
    <time_frame>18 weeks</time_frame>
    <description>Change from baseline in the overall z score for the motor function domain, calculated as the average of z scores from: grooved pegboard completion times for dominant and non-dominant hands.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Neurocognitive Performance: Language</measure>
    <time_frame>18 weeks</time_frame>
    <description>Change from baseline in the overall z score for the language domain, calculated as the average of z scores from: D-KEFS Letter and Category Verbal Fluency Tasks</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change from baseline in HQoL questionnaire score</measure>
    <time_frame>18 weeks</time_frame>
    <description>Change from baseline in health-related quality of life (HQoL) questionnaire score</description>
  </other_outcome>
  <other_outcome>
    <measure>Change from baseline in the PHQ-9 Questionnaire score</measure>
    <time_frame>18 weeks</time_frame>
    <description>Change in the Patient Health Questionnaire-9 (PHQ-9) depressive symptoms score.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change from Baseline in the Frailty Index Score - questionnaire and clinic assessment</measure>
    <time_frame>16 weeks</time_frame>
    <description>Change in the overall Frailty Index score measured from baseline to Week 8.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change from Baseline HAND inflammasome biomarker laboratory result profile</measure>
    <time_frame>16 weeks</time_frame>
    <description>Change in inflammasome biomarker laboratory result profile between baseline and week 16.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change from Baseline HAND metabolomics biomarker laboratory result profile</measure>
    <time_frame>16 weeks</time_frame>
    <description>Change in metabolomics biomarker laboratory result profile between baseline and week 16.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change from Baseline plasma HIV-1 viral load laboratory result</measure>
    <time_frame>16 weeks</time_frame>
    <description>Change in plasma HIV-1 viral load between baseline and week 16.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change from Baseline blood CD4 T-cell count laboratory result</measure>
    <time_frame>16 weeks</time_frame>
    <description>Change in blood CD4 T-cell count between baseline and week 16.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>HIV Associated Neurocognitive Disorder (HAND)</condition>
  <arm_group>
    <arm_group_label>IN insulin 40 IU</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Drug: IN insulin Dosage form: intranasal Dose: 40 IU Frequency: bid Duration: 16 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IN Sterile Saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Drug: Sterile Saline Dosage form: intranasal Frequency: bid Duration: 16 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>IN insulin</intervention_name>
    <description>IN insulin twice daily taken after breakfast and again after dinner using the nasal delivery device.</description>
    <arm_group_label>IN insulin 40 IU</arm_group_label>
    <other_name>Intranasal Humulin R</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Sterile Saline placebo</intervention_name>
    <description>Sterile Saline placebo twice daily taken after breakfast and again after dinner using the nasal delivery device.</description>
    <arm_group_label>IN Sterile Saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Documented HIV-1 infection&#xD;
&#xD;
          -  Maintained on stable ART for ≥6 months (defined as undetectable viral load)&#xD;
&#xD;
          -  HAND-MND or -ANI diagnosis with evidence of clinical onset or progression within the&#xD;
             prior 2 years, based on established criteria&#xD;
&#xD;
          -  Currently followed at the Southern Alberta Clinic (SAC; Calgary, AB, Canada)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  HAND with a) changed dose of any medication for HIV-1 infection with a corresponding&#xD;
             increase in viral load (e.g., ART), or b) secondary therapies for HAND (e.g.,&#xD;
             memantine, amphetamines).&#xD;
&#xD;
          -  Advanced liver, renal or lung disease, cancer or diabetes requiring insulin&#xD;
&#xD;
          -  Secondary diagnosis of neurocognitive impairment or other major neuropsychiatric&#xD;
             illness such as epilepsy, Alzheimer's or Parkinson's diseases, major depression (PHQ-9&#xD;
             score &gt;10), or schizophrenia&#xD;
&#xD;
          -  Central nervous system lesion (diagnosed by neuroimaging) that may impair cognition&#xD;
&#xD;
          -  Previous allergic reaction to insulin or any of the carrier components.&#xD;
&#xD;
          -  Education &lt; 9 years or inability to read and write English fluently&#xD;
&#xD;
          -  Uncontrolled HIV-1 or hepatitis C co-infection&#xD;
&#xD;
          -  Inability to perform NP or questionnaire measures, functional illiteracy&#xD;
&#xD;
          -  Past or current substance abuse that could interfere with the study assessments as&#xD;
             determined by the PI&#xD;
&#xD;
          -  Marijuana use on the day of NP testing&#xD;
&#xD;
          -  Uncontrolled cardiovascular disease (hypertension, coronary or peripheral artery&#xD;
             disease)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christopher Power, MD, FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Alberta</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Michael J Gill, MBChB FACP</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Calgary</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Southern Alberta Clinic</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2R 0X7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <link>
    <url>https://www.ualberta.ca/department-of-medicine/powerlab</url>
    <description>The Brain Power Lab</description>
  </link>
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  <reference>
    <citation>Power C, Boisse L, Rourke S, Gill MJ. NeuroAIDS: an evolving epidemic. Can J Neurol Sci. 2009 May;36(3):285-95. doi: 10.1017/s0317167100007009.</citation>
    <PMID>19534327</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>August 28, 2017</study_first_submitted>
  <study_first_submitted_qc>September 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 8, 2017</study_first_posted>
  <last_update_submitted>June 9, 2020</last_update_submitted>
  <last_update_submitted_qc>June 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Calgary</investigator_affiliation>
    <investigator_full_name>John Gill</investigator_full_name>
    <investigator_title>Medical Director, Southern Alberta Clinic</investigator_title>
  </responsible_party>
  <keyword>Neurocognitive impairment</keyword>
  <keyword>HIV-1</keyword>
  <keyword>Intranasal insulin</keyword>
  <keyword>Neurocognitive Disorder</keyword>
  <keyword>Cognition</keyword>
  <keyword>Memory</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neurocognitive Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin</mesh_term>
  </intervention_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/NCT03277222
org study id: REB17-0104
secondary id: Control# 204512
nct id: NCT03277222
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study aims to see whether intranasal insulin is an effective treatment for problems with
      memory, concentration, slowed thinking, or any other cognitive function in people living with
      HIV/AIDS. This group of signs and symptoms are called 'HIV-associated neurocognitive
      disorders' or HAND. HAND can affect people living with HIV/AIDS even when they receive potent
      anti-HIV treatments. Treatment of HAND by specific medication or other means is not yet
      available. Intranasal insulin treatment has virtually no side-effects, and has already been
      tested in people with Alzheimer's disease, where it showed beneficial effects on memory, mood
      and quality of life
This study is designed as a prospective, double-blinded pilot study of intranasal (IN)
      insulin versus placebo in people with HAND (n = 20) on stable ART medication. Participants
      will be randomly assigned to one of two groups: 40 IU IN insulin R twice daily, or
      matched-volume placebo, which will be administered twice daily, taken after breakfast and
      again after dinner using a nasal delivery device. Serum glucose will be tested for
      hypoglycemia one hour after the initial administration of IN insulin or placebo and after
      administration at Weeks 1, 2, and 3. If the dose is tolerated and no side effects are
      reported the participant will continue in the study. If the dose is not tolerated due to
      hypoglycemia then the participant will be withdrawn from the study.

      The objectives of this study are as follows:

      Primary: Determine if IN insulin treatment administered twice daily for 4 months reduces
      overall neurocognitive deficits (based on the global z-score in people with HAND).

      Secondary: Measure effects of IN insulin on individual neuropsychological domains (e.g.,
      memory, processing speed, executive functions, motor functions) and on HAND disease
      progression; Define impacts of IN insulin on quality of life and mood in people with HAND;
      Investigate IN insulin's effects on HAND biomarker profiles in urine and blood.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Arm 1: Drug: IN insulin Dose: Twice daily IN insulin R at 40 IU (n=10) twice daily using a nasal delivery device. IN insulin R will be administered twice daily.
Arm 2: Drug: Sterile Saline placebo Dose: Placebo (Sterile Saline placebo, matched volume; (n=10) twice daily using nasal delivery device.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: This is a prospective dose-ranging double-blinded pilot study over 4 months. At enrolment, participants and their physicians will be blinded to treatment.
measure: Change in Global Neurocognitive Performance from Baseline
time frame: 18 weeks
description: Change in overall neurocognitive function as measured by the global z score. The global z score is one measurement calculated as the average of z scores from each domain tested.
measure: Change from Baseline in Neurocognitive Performance: Memory
time frame: 18 weeks
description: Change from baseline in the overall z score for the memory domain, calculated as the average of z scores from: Hopkins Verbal Learning Test, Logical Memory Test, and Brief Visual Memory Test (immediate and delayed recall).
measure: Change from Baseline in Neurocognitive Performance: Executive Function
time frame: 18 weeks
description: Change from baseline in the overall z score for the executive function domain, calculated as the average of z scores from: D-KEFS Trail-making Task (Letter-Switching) and Color-Word Interference (Stroop).
measure: Change from Baseline in Neurocognitive Performance: Attention
time frame: 18 weeks
description: Change from baseline in the overall z score for the attention domain, calculated as the average of z scores from: Symbol Digit Modalities Test, D-KEFS Trail-making Test (Number), and Color-Word Interference (Color and Word Reading).
measure: Change from Baseline in Neurocognitive Performance: Motor Function
time frame: 18 weeks
description: Change from baseline in the overall z score for the motor function domain, calculated as the average of z scores from: grooved pegboard completion times for dominant and non-dominant hands.
measure: Change from Baseline in Neurocognitive Performance: Language
time frame: 18 weeks
description: Change from baseline in the overall z score for the language domain, calculated as the average of z scores from: D-KEFS Letter and Category Verbal Fluency Tasks
measure: Change from baseline in HQoL questionnaire score
time frame: 18 weeks
description: Change from baseline in health-related quality of life (HQoL) questionnaire score
measure: Change from baseline in the PHQ-9 Questionnaire score
time frame: 18 weeks
description: Change in the Patient Health Questionnaire-9 (PHQ-9) depressive symptoms score.
measure: Change from Baseline in the Frailty Index Score - questionnaire and clinic assessment
time frame: 16 weeks
description: Change in the overall Frailty Index score measured from baseline to Week 8.
measure: Change from Baseline HAND inflammasome biomarker laboratory result profile
time frame: 16 weeks
description: Change in inflammasome biomarker laboratory result profile between baseline and week 16.
measure: Change from Baseline HAND metabolomics biomarker laboratory result profile
time frame: 16 weeks
description: Change in metabolomics biomarker laboratory result profile between baseline and week 16.
measure: Change from Baseline plasma HIV-1 viral load laboratory result
time frame: 16 weeks
description: Change in plasma HIV-1 viral load between baseline and week 16.
measure: Change from Baseline blood CD4 T-cell count laboratory result
time frame: 16 weeks
description: Change in blood CD4 T-cell count between baseline and week 16.
arm group label: IN insulin 40 IU
arm group type: Active Comparator
description: Drug: IN insulin Dosage form: intranasal Dose: 40 IU Frequency: bid Duration: 16 weeks
arm group label: IN Sterile Saline
arm group type: Placebo Comparator
description: Drug: Sterile Saline Dosage form: intranasal Frequency: bid Duration: 16 weeks
intervention type: Biological
intervention name: IN insulin
description: IN insulin twice daily taken after breakfast and again after dinner using the nasal delivery device.
arm group label: IN insulin 40 IU
other name: Intranasal Humulin R
intervention type: Biological
intervention name: Sterile Saline placebo
description: Sterile Saline placebo twice daily taken after breakfast and again after dinner using the nasal delivery device.
arm group label: IN Sterile Saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Christopher Power, MD, FRCPC
role: Principal Investigator
affiliation: University of Alberta
last name: Michael J Gill, MBChB FACP
role: Principal Investigator
affiliation: University of Calgary
facility: 
country: Canada
url: https://www.ualberta.ca/department-of-medicine/powerlab
description: The Brain Power Lab
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PMID: 17914061
citation: Pandya R, Krentz HB, Gill MJ, Power C. HIV-related neurological syndromes reduce health-related quality of life. Can J Neurol Sci. 2005 May;32(2):201-4. doi: 10.1017/s0317167100003978.
PMID: 16018155
citation: Yeung H, Krentz HB, Gill MJ, Power C. Neuropsychiatric disorders in HIV infection: impact of diagnosis on economic costs of care. AIDS. 2006 Oct 24;20(16):2005-9. doi: 10.1097/01.aids.0000247565.80633.d2.
PMID: 17053346
citation: Vivithanaporn P, Heo G, Gamble J, Krentz HB, Hoke A, Gill MJ, Power C. Neurologic disease burden in treated HIV/AIDS predicts survival: a population-based study. Neurology. 2010 Sep 28;75(13):1150-8. doi: 10.1212/WNL.0b013e3181f4d5bb. Epub 2010 Aug 25.
PMID: 20739646
citation: Mamik MK, Asahchop EL, Chan WF, Zhu Y, Branton WG, McKenzie BA, Cohen EA, Power C. Insulin Treatment Prevents Neuroinflammation and Neuronal Injury with Restored Neurobehavioral Function in Models of HIV/AIDS Neurodegeneration. J Neurosci. 2016 Oct 12;36(41):10683-10695. doi: 10.1523/JNEUROSCI.1287-16.2016.
PMID: 27733618
citation: Boisse L, Gill MJ, Power C. HIV infection of the central nervous system: clinical features and neuropathogenesis. Neurol Clin. 2008 Aug;26(3):799-819, x. doi: 10.1016/j.ncl.2008.04.002.
PMID: 18657727
citation: Fujiwara, E., Gill, J.M. & Power, C. Risk Factors for HIV-Associated Neurocognitive Disorders (HAND) in a Canadian Cohort (P1.321). Neurology 86 P1.321 (2016).
citation: McCombe JA, Vivithanaporn P, Gill MJ, Power C. Predictors of symptomatic HIV-associated neurocognitive disorders in universal health care. HIV Med. 2013 Feb;14(2):99-107. doi: 10.1111/j.1468-1293.2012.01043.x. Epub 2012 Sep 20.
PMID: 22994556
citation: Grant I, Franklin DR Jr, Deutsch R, Woods SP, Vaida F, Ellis RJ, Letendre SL, Marcotte TD, Atkinson JH, Collier AC, Marra CM, Clifford DB, Gelman BB, McArthur JC, Morgello S, Simpson DM, McCutchan JA, Abramson I, Gamst A, Fennema-Notestine C, Smith DM, Heaton RK; CHARTER Group. Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline. Neurology. 2014 Jun 10;82(23):2055-62. doi: 10.1212/WNL.0000000000000492. Epub 2014 May 9.
PMID: 24814848
citation: Sacktor N, Skolasky RL, Seaberg E, Munro C, Becker JT, Martin E, Ragin A, Levine A, Miller E. Prevalence of HIV-associated neurocognitive disorders in the Multicenter AIDS Cohort Study. Neurology. 2016 Jan 26;86(4):334-40. doi: 10.1212/WNL.0000000000002277. Epub 2015 Dec 30.
PMID: 26718568
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PMID: 25316020
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PMID: 18195140
citation: Hyun E, Ramachandran R, Hollenberg MD, Vergnolle N. Mechanisms behind the anti-inflammatory actions of insulin. Crit Rev Immunol. 2011;31(4):307-40. doi: 10.1615/critrevimmunol.v31.i4.30.
PMID: 21899513
citation: Benedict C, Hallschmid M, Hatke A, Schultes B, Fehm HL, Born J, Kern W. Intranasal insulin improves memory in humans. Psychoneuroendocrinology. 2004 Nov;29(10):1326-34. doi: 10.1016/j.psyneuen.2004.04.003.
PMID: 15288712
citation: Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, Arbuckle M, Callaghan M, Tsai E, Plymate SR, Green PS, Leverenz J, Cross D, Gerton B. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol. 2012 Jan;69(1):29-38. doi: 10.1001/archneurol.2011.233. Epub 2011 Sep 12.
PMID: 21911655
citation: Rosenbloom MH, Barclay TR, Pyle M, Owens BL, Cagan AB, Anderson CP, Frey WH 2nd, Hanson LR. A single-dose pilot trial of intranasal rapid-acting insulin in apolipoprotein E4 carriers with mild-moderate Alzheimer's disease. CNS Drugs. 2014 Dec;28(12):1185-9. doi: 10.1007/s40263-014-0214-y.
PMID: 25373630
citation: Claxton A, Baker LD, Wilkinson CW, Trittschuh EH, Chapman D, Watson GS, Cholerton B, Plymate SR, Arbuckle M, Craft S. Sex and ApoE genotype differences in treatment response to two doses of intranasal insulin in adults with mild cognitive impairment or Alzheimer's disease. J Alzheimers Dis. 2013;35(4):789-97. doi: 10.3233/JAD-122308.
PMID: 23507773
citation: Claxton A, Baker LD, Hanson A, Trittschuh EH, Cholerton B, Morgan A, Callaghan M, Arbuckle M, Behl C, Craft S. Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer's disease dementia. J Alzheimers Dis. 2015;44(3):897-906. doi: 10.3233/JAD-141791. Erratum In: J Alzheimers Dis. 2015;45(4):1269-70.
PMID: 25374101
citation: Reger MA, Watson GS, Green PS, Wilkinson CW, Baker LD, Cholerton B, Fishel MA, Plymate SR, Breitner JC, DeGroodt W, Mehta P, Craft S. Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology. 2008 Feb 5;70(6):440-8. doi: 10.1212/01.WNL.0000265401.62434.36. Epub 2007 Oct 17. Erratum In: Neurology. 2008 Sep 9;71(11):866.
PMID: 17942819
citation: Shemesh E, Rudich A, Harman-Boehm I, Cukierman-Yaffe T. Effect of intranasal insulin on cognitive function: a systematic review. J Clin Endocrinol Metab. 2012 Feb;97(2):366-76. doi: 10.1210/jc.2011-1802. Epub 2011 Dec 7.
PMID: 22162476
citation: Asahchop EL, Akinwumi SM, Branton WG, Fujiwara E, Gill MJ, Power C. Plasma microRNA profiling predicts HIV-associated neurocognitive disorder. AIDS. 2016 Aug 24;30(13):2021-31. doi: 10.1097/QAD.0000000000001160.
PMID: 27191977
citation: Lenart N, Brough D, Denes A. Inflammasomes link vascular disease with neuroinflammation and brain disorders. J Cereb Blood Flow Metab. 2016 Oct;36(10):1668-1685. doi: 10.1177/0271678X16662043. Epub 2016 Aug 2.
PMID: 27486046
citation: Walsh JG, Muruve DA, Power C. Inflammasomes in the CNS. Nat Rev Neurosci. 2014 Feb;15(2):84-97. doi: 10.1038/nrn3638. Epub 2014 Jan 8.
PMID: 24399084
citation: Kim DH, Jewison DL, Milner GR, Rourke SB, Gill MJ, Power C. Neurocognitive symptoms and impairment in an HIV community clinic. Can J Neurol Sci. 2001 Aug;28(3):228-31. doi: 10.1017/s0317167100001372.
PMID: 11513341
citation: Koenig N, Fujiwara E, Gill MJ, Power C. Montreal Cognitive Assessment Performance in HIV/AIDS: Impact of Systemic Factors. Can J Neurol Sci. 2016 Jan;43(1):157-62. doi: 10.1017/cjn.2015.306. Epub 2015 Dec 4.
PMID: 26635008
citation: Fujiwara E, Tomlinson SE, Purdon SE, Gill MJ, Power C. Decision making under explicit risk is impaired in individuals with human immunodeficiency virus (HIV). J Clin Exp Neuropsychol. 2015;37(7):733-50. doi: 10.1080/13803395.2015.1057481. Epub 2015 Jul 24.
PMID: 26207583
citation: Justice AC, McGinnis KA, Atkinson JH, Heaton RK, Young C, Sadek J, Madenwald T, Becker JT, Conigliaro J, Brown ST, Rimland D, Crystal S, Simberkoff M; Veterans Aging Cohort 5-Site Study Project Team. Psychiatric and neurocognitive disorders among HIV-positive and negative veterans in care: Veterans Aging Cohort Five-Site Study. AIDS. 2004 Jan 1;18 Suppl 1:S49-59.
PMID: 15075498
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PMID: 16548713
citation: Power C, Gill MJ, Johnson RT. Progress in clinical neurosciences: The neuropathogenesis of HIV infection: host-virus interaction and the impact of therapy. Can J Neurol Sci. 2002 Feb;29(1):19-32. doi: 10.1017/s0317167100001682.
PMID: 11858531
citation: Van Marle G, Rourke SB, Zhang K, Silva C, Ethier J, Gill MJ, Power C. HIV dementia patients exhibit reduced viral neutralization and increased envelope sequence diversity in blood and brain. AIDS. 2002 Sep 27;16(14):1905-14. doi: 10.1097/00002030-200209270-00007.
PMID: 12351950
citation: Skinner S, Adewale AJ, DeBlock L, Gill MJ, Power C. Neurocognitive screening tools in HIV/AIDS: comparative performance among patients exposed to antiretroviral therapy. HIV Med. 2009 Apr;10(4):246-52. doi: 10.1111/j.1468-1293.2008.00679.x. Epub 2009 Jan 23.
PMID: 19187172
citation: McCombe JA, Auer RN, Maingat FG, Houston S, Gill MJ, Power C. Neurologic immune reconstitution inflammatory syndrome in HIV/AIDS: outcome and epidemiology. Neurology. 2009 Mar 3;72(9):835-41. doi: 10.1212/01.wnl.0000343854.80344.69.
PMID: 19255411
citation: Sacktor, N., et al. Paroxetine and Fluconazole Therapy for HAND: A Double-Blind, Placebo-Controlled Trial. Conference on retroviruses and opportunistic infections. 2016 Boston MA USA Sesssion O-12 Abstract 146(2016).
citation: Power C, Boisse L, Rourke S, Gill MJ. NeuroAIDS: an evolving epidemic. Can J Neurol Sci. 2009 May;36(3):285-95. doi: 10.1017/s0317167100007009.
PMID: 19534327
responsible party type: Principal Investigator
investigator affiliation: University of Calgary
investigator full name: John Gill
investigator title: Medical Director, Southern Alberta Clinic
mesh term: Neurocognitive Disorders
mesh term: Insulin
sharing ipd: No