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HIV Associated Neurocognitive Disorder (HAND)Phase 2NCT03277222

Intranasal Treatment of HIV-associated Neurocognitive Disorders

A Phase 2 study testing IN insulin in people with HIV Associated Neurocognitive Disorder (HAND), run by University of Calgary at 1 site in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
IN insulin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
4 participants
Where
1 siteCanada
Study dates
1 Nov 2018to 21 Apr 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 11Show fewer
  • 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)

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Southern Alberta Clinic

    Calgary, Alberta, T2R 0X7

Other trials in Canada

About this study

Official title: 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

Read the 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.

Being tested
IN insulin, Sterile Saline placebo
Keywords
Neurocognitive impairment, HIV-1, Intranasal insulin, Neurocognitive Disorder, Cognition, Memory
Medical subject headings
Neurocognitive Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IN insulinBiological

    Also called Intranasal Humulin R

    IN insulin twice daily taken after breakfast and again after dinner using the nasal delivery device.

  • Sterile Saline placeboBiological

    Sterile Saline placebo twice daily taken after breakfast and again after dinner using the nasal delivery device.

Study groups in NCT03277222
Study groupRoleWhat they receive
IN insulin 40 IUActive comparatorDrug: IN insulin Dosage form: intranasal Dose: 40 IU Frequency: bid Duration: 16 weeks
Receives: Biological: IN insulin
IN Sterile SalinePlacebo comparatorDrug: Sterile Saline Dosage form: intranasal Frequency: bid Duration: 16 weeks
Receives: Biological: Sterile Saline placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Global Neurocognitive Performance from Baseline

    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.

    Measured: 18 weeks

Secondary outcomes (5)

  1. Change from Baseline in Neurocognitive Performance: Memory

    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).

    Measured: 18 weeks

  2. Change from Baseline in Neurocognitive Performance: Executive Function

    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).

    Measured: 18 weeks

  3. Change from Baseline in Neurocognitive Performance: Attention

    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).

    Measured: 18 weeks

  4. Change from Baseline in Neurocognitive Performance: Motor Function

    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.

    Measured: 18 weeks

  5. Change from Baseline in Neurocognitive Performance: Language

    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

    Measured: 18 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Sep 2017
  2. Study start1 Nov 2018
  3. Primary completion21 Apr 2019
  4. Study completion21 Apr 2019

Why it stopped: Unable to find further eligible participants

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
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 blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03277222
Sponsor's protocol ID
REB17-0104
Other IDs
Control# 204512
Status last verified
Jun 2020
First submitted
28 Aug 2017
Last updated
11 Jun 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007 Oct 30;69(18):1789-99. doi: 10.1212/01.WNL.0000287431.88658.8b. Epub 2007 Oct 3.

    PubMed 17914061

  • 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.

    PubMed 16018155

  • 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.

    PubMed 17053346

  • 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.

    PubMed 20739646

  • 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.

    PubMed 27733618

  • 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.

    PubMed 18657727

  • 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).

  • 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.

    PubMed 22994556

  • 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.

    PubMed 24814848

  • 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.

    PubMed 26718568

  • Nightingale S, Winston A, Letendre S, Michael BD, McArthur JC, Khoo S, Solomon T. Controversies in HIV-associated neurocognitive disorders. Lancet Neurol. 2014 Nov;13(11):1139-1151. doi: 10.1016/S1474-4422(14)70137-1.

    PubMed 25316020

  • Letendre S, Marquie-Beck J, Capparelli E, Best B, Clifford D, Collier AC, Gelman BB, McArthur JC, McCutchan JA, Morgello S, Simpson D, Grant I, Ellis RJ; CHARTER Group. Validation of the CNS Penetration-Effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol. 2008 Jan;65(1):65-70. doi: 10.1001/archneurol.2007.31.

    PubMed 18195140

  • 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.

    PubMed 21899513

  • 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.

    PubMed 15288712

  • 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.

    PubMed 21911655

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IN insulin in people with HIV Associated Neurocognitive Disorder (HAND), run by University of Calgary at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 11 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Unable to find further eligible participants). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Global Neurocognitive Performance from Baseline (time frame: 18 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03277222, which also lists 34 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2020.

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