HIV Associated Neurocognitive Disorder (HAND)
Conditions
Keywords
Neurocognitive impairment, HIV-1, Intranasal insulin, Neurocognitive Disorder, Cognition, Memory
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 If the dose is not tolerated due to hypoglycemia then the participant will be withdrawn from the study.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.
Interventions
BIOLOGICALIN insulin
IN insulin twice daily taken after breakfast and again after dinner using the nasal delivery device.
BIOLOGICALSterile Saline placebo
Sterile Saline placebo twice daily taken after breakfast and again after dinner using the nasal delivery device.
Sponsors
Canadian Institutes of Health Research (CIHR)
University of Alberta
Epidemiology Coordinating and Research Centre, Canada
University of Calgary
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, 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.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Global Neurocognitive Performance from Baseline | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Neurocognitive Performance: Memory | 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 | 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 | 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 | 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 | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in HQoL questionnaire score | 18 weeks | Change from baseline in health-related quality of life (HQoL) questionnaire score |
| Change from Baseline blood CD4 T-cell count laboratory result | 16 weeks | Change in blood CD4 T-cell count between baseline and week 16. |
| Change from baseline in the PHQ-9 Questionnaire score | 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 | 16 weeks | Change in the overall Frailty Index score measured from baseline to Week 8. |
| Change from Baseline HAND inflammasome biomarker laboratory result profile | 16 weeks | Change in inflammasome biomarker laboratory result profile between baseline and week 16. |
| Change from Baseline HAND metabolomics biomarker laboratory result profile | 16 weeks | Change in metabolomics biomarker laboratory result profile between baseline and week 16. |
| Change from Baseline plasma HIV-1 viral load laboratory result | 16 weeks | Change in plasma HIV-1 viral load between baseline and week 16. |
Countries
Canada
Outcome results
None listed