Clinical trial NCT03277222: Intranasal Treatment of HIV-associated Neurocognitive Disorders
Official title: HAND IN Insulin-001: Intranasal Treatment of HIV-associated Neurocognitive Disorders
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: HIV Associated Neurocognitive Disorder (HAND)
Keywords: Neurocognitive impairment
HIV-1
Intranasal insulin
Neurocognitive Disorder
Cognition
Memory
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: University of Alberta
name: Epidemiology Coordinating and Research Centre, Canada
First posted: 2017-09-08
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change in Global Neurocognitive Performance from Baseline
timeFrame: 18 weeks
Secondary outcomes:
measure: Change from Baseline in Neurocognitive Performance: Memory
timeFrame: 18 weeks
measure: Change from Baseline in Neurocognitive Performance: Executive Function
timeFrame: 18 weeks
measure: Change from Baseline in Neurocognitive Performance: Attention
timeFrame: 18 weeks
measure: Change from Baseline in Neurocognitive Performance: Motor Function
timeFrame: 18 weeks
measure: Change from Baseline in Neurocognitive Performance: Language
timeFrame: 18 weeks
Other outcomes:
measure: Change from baseline in HQoL questionnaire score
timeFrame: 18 weeks
measure: Change from baseline in the PHQ-9 Questionnaire score
timeFrame: 18 weeks
measure: Change from Baseline in the Frailty Index Score - questionnaire and clinic assessment
timeFrame: 16 weeks
measure: Change from Baseline HAND inflammasome biomarker laboratory result profile
timeFrame: 16 weeks
measure: Change from Baseline HAND metabolomics biomarker laboratory result profile
timeFrame: 16 weeks
measure: Change from Baseline plasma HIV-1 viral load laboratory result
timeFrame: 16 weeks
measure: Change from Baseline blood CD4 T-cell count laboratory result
timeFrame: 16 weeks
Locations:
city: Calgary
country: Canada
facility: Southern Alberta Clinic
state: Alberta
Study officials:
affiliation: University of Alberta
name: Christopher Power, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Calgary
name: Michael J Gill, MBChB FACP
role: PRINCIPAL_INVESTIGATOR
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