Intranasal Treatment of HIV-associated Neurocognitive Disorders

University of Calgary

Status and phase

Terminated

Phase 2

Conditions

HIV Associated Neurocognitive Disorder (HAND)

Treatments

Biological: Sterile Saline placebo

Biological: IN insulin

Study type

Interventional

Funder types

Other

Identifiers

NCT03277222

Control# 204512 (Other Identifier)

REB17-0104

Details and patient eligibility

About

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

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 If the dose is not tolerated due to hypoglycemia then the participant will be withdrawn from the study.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

Enrollment

4 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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)