Intranasal Treatment of HIV-associated Neurocognitive Disorders

Phase 2TerminatedNCT03277222

University of Calgary4 enrolled

Overview

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

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 If the dose is not tolerated due to hypoglycemia then the participant will be withdrawn from the study.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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

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.

Time frame: 18 weeks

Secondary Outcomes

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).

Time frame: 18 weeks

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).

Time frame: 18 weeks

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).

Time frame: 18 weeks

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.

Time frame: 18 weeks

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

Time frame: 18 weeks

Intranasal Treatment of HIV-associated Neurocognitive Disorders

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes