Intranasal Treatment of HIV-associated Neurocognitive Disorders

June 9, 2020 updated by: John Gill, University of Calgary

HAND IN Insulin-001: Intranasal Treatment of HIV-associated Neurocognitive Disorders

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 If the dose is not tolerated due to hypoglycemia then the participant will be withdrawn from the study.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

Interventional

Enrollment (Actual)

4

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2R 0X7
        • Southern Alberta Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: IN insulin 40 IU
Drug: IN insulin Dosage form: intranasal Dose: 40 IU Frequency: bid Duration: 16 weeks
Biological: IN insulin
IN insulin twice daily taken after breakfast and again after dinner using the nasal delivery device.
Other Names:
  • Intranasal Humulin R
Placebo Comparator: IN Sterile Saline
Drug: Sterile Saline Dosage form: intranasal Frequency: bid Duration: 16 weeks
Biological: Sterile Saline placebo
Sterile Saline placebo twice daily taken after breakfast and again after dinner using the nasal delivery device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
18 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
18 weeks
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).
18 weeks
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).
18 weeks
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.
18 weeks
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
18 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in HQoL questionnaire score
Time Frame: 18 weeks
Change from baseline in health-related quality of life (HQoL) questionnaire score
18 weeks
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.
18 weeks
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.
16 weeks
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.
16 weeks
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.
16 weeks
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.
16 weeks
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.
16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Calgary

Collaborators

Canadian Institutes of Health Research (CIHR)
University of Alberta
Epidemiology Coordinating and Research Centre, Canada

Investigators

  • Principal Investigator: Christopher Power, MD, FRCPC, University of Alberta
  • Principal Investigator: Michael J Gill, MBChB FACP, University of Calgary

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2018

Primary Completion (Actual)

April 21, 2019

Study Completion (Actual)

April 21, 2019

Study Registration Dates

First Submitted

August 28, 2017

First Submitted That Met QC Criteria

September 6, 2017

First Posted (Actual)

September 8, 2017

Study Record Updates

Last Update Posted (Actual)

June 11, 2020

Last Update Submitted That Met QC Criteria

June 9, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • REB17-0104
  • Control# 204512 (Other Identifier: Health Canada)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on HIV Associated Neurocognitive Disorder (HAND)

Clinical Trials on IN insulin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Slovakia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe