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Intranasal Treatment of HIV-associated Neurocognitive Disorders

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ClinicalTrials.gov Identifier: NCT03277222
Recruitment Status : Terminated (Unable to find further eligible participants)
First Posted : September 8, 2017
Last Update Posted : June 11, 2020
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
University of Alberta
Epidemiology Coordinating and Research Centre, Canada
Information provided by (Responsible Party):
John Gill, University of Calgary

Tracking Information
First Submitted Date  ICMJE August 28, 2017
First Posted Date  ICMJE September 8, 2017
Last Update Posted Date June 11, 2020
Actual Study Start Date  ICMJE November 1, 2018
Actual Primary Completion Date April 21, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 6, 2017)
Change in Global Neurocognitive Performance from Baseline [ Time Frame: 18 weeks ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 6, 2017)
  • Change from Baseline in Neurocognitive Performance: Memory [ Time Frame: 18 weeks ]
    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).
  • Change from Baseline in Neurocognitive Performance: Executive Function [ Time Frame: 18 weeks ]
    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).
  • Change from Baseline in Neurocognitive Performance: Attention [ Time Frame: 18 weeks ]
    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).
  • Change from Baseline in Neurocognitive Performance: Motor Function [ Time Frame: 18 weeks ]
    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.
  • Change from Baseline in Neurocognitive Performance: Language [ Time Frame: 18 weeks ]
    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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 25, 2017)
  • Change from baseline in HQoL questionnaire score [ Time Frame: 18 weeks ]
    Change from baseline in health-related quality of life (HQoL) questionnaire score
  • Change from baseline in the PHQ-9 Questionnaire score [ Time Frame: 18 weeks ]
    Change in the Patient Health Questionnaire-9 (PHQ-9) depressive symptoms score.
  • Change from Baseline in the Frailty Index Score - questionnaire and clinic assessment [ Time Frame: 16 weeks ]
    Change in the overall Frailty Index score measured from baseline to Week 8.
  • Change from Baseline HAND inflammasome biomarker laboratory result profile [ Time Frame: 16 weeks ]
    Change in inflammasome biomarker laboratory result profile between baseline and week 16.
  • Change from Baseline HAND metabolomics biomarker laboratory result profile [ Time Frame: 16 weeks ]
    Change in metabolomics biomarker laboratory result profile between baseline and week 16.
  • Change from Baseline plasma HIV-1 viral load laboratory result [ Time Frame: 16 weeks ]
    Change in plasma HIV-1 viral load between baseline and week 16.
  • Change from Baseline blood CD4 T-cell count laboratory result [ Time Frame: 16 weeks ]
    Change in blood CD4 T-cell count between baseline and week 16.
Original Other Pre-specified Outcome Measures
 (submitted: September 6, 2017)
  • Change from baseline in HQoL [ Time Frame: 18 weeks ]
    Change from baseline in health-related quality of life (HQoL)
  • Change from baseline in the PHQ-9 score [ Time Frame: 18 weeks ]
    Change in the Patient Health Questionnaire-9 (PHQ-9) depressive symptoms score.
  • Change from Baseline in the Frailty Index Score [ Time Frame: 16 weeks ]
    Change in the overall Frailty Index score measured from baseline to Week 8.
  • Change from Baseline HAND inflammasome biomarker profile [ Time Frame: 16 weeks ]
    Change in inflammasome biomarker profile between baseline and week 16.
  • Change from Baseline HAND metabolomics biomarker profile [ Time Frame: 16 weeks ]
    Change in metabolomics biomarker profile between baseline and week 16.
  • Change from Baseline plasma HIV-1 viral load [ Time Frame: 16 weeks ]
    Change in plasma HIV-1 viral load between baseline and week 16.
  • Change from Baseline blood CD4 T-cell count [ Time Frame: 16 weeks ]
    Change in blood CD4 T-cell count between baseline and week 16.
 
Descriptive Information
Brief Title  ICMJE Intranasal Treatment of HIV-associated Neurocognitive Disorders
Official Title  ICMJE HAND IN Insulin-001: Intranasal Treatment of HIV-associated Neurocognitive Disorders
Brief Summary 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
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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.

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.
Primary Purpose: Treatment
Condition  ICMJE HIV Associated Neurocognitive Disorder (HAND)
Intervention  ICMJE
  • Biological: IN insulin
    IN insulin twice daily taken after breakfast and again after dinner using the nasal delivery device.
    Other Name: Intranasal Humulin R
  • Biological: Sterile Saline placebo
    Sterile Saline placebo twice daily taken after breakfast and again after dinner using the nasal delivery device.
Study Arms  ICMJE
  • Active Comparator: IN insulin 40 IU
    Drug: IN insulin Dosage form: intranasal Dose: 40 IU Frequency: bid Duration: 16 weeks
    Intervention: Biological: IN insulin
  • Placebo Comparator: IN Sterile Saline
    Drug: Sterile Saline Dosage form: intranasal Frequency: bid Duration: 16 weeks
    Intervention: Biological: Sterile Saline placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 9, 2020)
4
Original Estimated Enrollment  ICMJE
 (submitted: September 6, 2017)
45
Actual Study Completion Date  ICMJE April 21, 2019
Actual Primary Completion Date April 21, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Documented HIV-1 infection
  • Maintained on stable ART for ≥6 months (defined as undetectable viral load)
  • HAND-MND or -ANI diagnosis with evidence of clinical onset or progression within the prior 2 years, based on established criteria
  • Currently followed at the Southern Alberta Clinic (SAC; Calgary, AB, Canada)

Exclusion Criteria:

  • HAND with a) changed dose of any medication for HIV-1 infection with a corresponding increase in viral load (e.g., ART), or b) secondary therapies for HAND (e.g., memantine, amphetamines).
  • Advanced liver, renal or lung disease, cancer or diabetes requiring insulin
  • Secondary diagnosis of neurocognitive impairment or other major neuropsychiatric illness such as epilepsy, Alzheimer's or Parkinson's diseases, major depression (PHQ-9 score >10), or schizophrenia
  • Central nervous system lesion (diagnosed by neuroimaging) that may impair cognition
  • Previous allergic reaction to insulin or any of the carrier components.
  • Education < 9 years or inability to read and write English fluently
  • Uncontrolled HIV-1 or hepatitis C co-infection
  • Inability to perform NP or questionnaire measures, functional illiteracy
  • Past or current substance abuse that could interfere with the study assessments as determined by the PI
  • Marijuana use on the day of NP testing
  • Uncontrolled cardiovascular disease (hypertension, coronary or peripheral artery disease)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03277222
Other Study ID Numbers  ICMJE REB17-0104
Control# 204512 ( Other Identifier: Health Canada )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party John Gill, University of Calgary
Study Sponsor  ICMJE University of Calgary
Collaborators  ICMJE
  • Canadian Institutes of Health Research (CIHR)
  • University of Alberta
  • Epidemiology Coordinating and Research Centre, Canada
Investigators  ICMJE
Principal Investigator: Christopher Power, MD, FRCPC University of Alberta
Principal Investigator: Michael J Gill, MBChB FACP University of Calgary
PRS Account University of Calgary
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP