Clinical Trial: Intranasal Insulin for the Treatment of HAND

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Clinical Trial of Intranasal Insulin for the Treatment of HIV-associated Neurocognitive Disorder (HAND)

Brief Summary:

Infection with HIV (the virus that causes AIDS) can lead to problems with brain function, such as memory, concentration, judgment, and the speed or control of hands and legs. Neurologists have called this condition HIV-associated neurocognitive disorder (HAND). This research is being done to see if insulin taken through the nose as a spray (intranasal insulin) can help people with HIV who are having problems with memory and brain function, or HAND.

Participants will be given either insulin or placebo. A placebo is an inactive substance that looks like the study drug, but does not contain study drug. For this research study, the placebo will be a clear, saline-based liquid spray that looks like the insulin spray but has no insulin. Participants will not be told whether they receive insulin or placebo during the study.

All participants will take the intranasal spray twice a day, about 30 minutes after a meal. Participants will use a specialized intranasal drug administration device. The total daily dose of insulin is 40 IU split between 20 IU in the morning and 20 IU in the evening. Participants will take the intranasal spray for 24 weeks.

The researchers will record symptoms and side effects during the study. Procedures include neurocognitive testing of memory and brain function, two lumbar punctures ("spinal taps"), two MRI brain scans, several blood draws, and clinical assessments.


Detailed Summary:

HIV-associated neurocognitive disorders (HAND) are characterized by disabling cognitive, behavioral, and motor dysfunction and can occur in individuals with HIV even while taking combination antiretroviral therapy (ART). The mechanisms for these residual impairments are not fully understood, but appear to involve poor penetrance of ART drugs into the central nervous system (CNS) and the resulting brain sanctuary for inadequately suppressed HIV infection with associated sustained inflammation. Adjunctive therapies with targeted neuroprotective agents are critically needed for the treatment of HAND. Insulin is involved in multiple CNS functions including food intake, metabolism, learning, and memory. Insulin has neuroprotective properties demonstrated in cell culture experiments and in vivo models, which provide strong evidence for its use as a therapeutic agent to treat HAND.

Insulin modifying therapy (IMT) includes intranasal insulin administered by a novel nasal drug delivery device. IMT may play important roles in neuronal plasticity and survival by protecting hippocampal neurons against oxidative stress and apoptotic cell death induced by glutamate neurotoxicity. Previous studies support the proposed early phase trial of IMT as a novel therapeutic agent for HAND.

This double-blinded placebo-controlled clinical trial evaluates safety of intranasal insulin at the daily dose of 40 IU and will provide initial data for assessing safety and efficacy. The protocol measures safety by incidence and frequency of adverse events. Clinical effects of IMT over the 24-week trial period are measured by change in neurocognitive and functional testing results, as well as several novel radiological and cerebrospinal fluid (CSF) surrogate markers. Outcomes from these studies could have important implications for the design of future studie
Sponsor: Johns Hopkins University

Current Primary Outcome:

  • Serious adverse event frequency [ Time Frame: Total during 24-week trial ]
    Number of documented serious adverse events per participant, mean
  • Global Deficit Score (GDS) [ Time Frame: Difference between baseline and week 24 visits ]
    Arithmetic change in GDS, a composite score based on neurocognitive testing performance


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • CSF biomarkers [ Time Frame: Between baseline and week 24 visits ]
    Changes in cerebrospinal fluid (CSF) concentrations of ceramide, sphingomyelin, citrate, neurofilament protein; brain-derived neurotrophic factor (BDNF), protein carbonyl, Aβ-42
  • Neuroimaging markers: SV-MRS [ Time Frame: Changes between baseline and week 24 visits ]
    Single voxel-magnetic resonance spectroscopy (SV-MRS) myoinositol, choline, and N-acetyl aspartate concentrations in frontal white matter and basal ganglia
  • Neuroimaging markers: DTI [ Time Frame: Changes between baseline and week 24 visits ]
    Diffusion tensor imaging (DTI) whole brain fractional anisotropy, DTI whole brain mean diffusivity.
  • Neuroimaging markers: ASL [ Time Frame: Changes between baseline and week 24 visits ]
    Arterial spin labeling (ASL), a novel measure of cerebral blood flow


Original Secondary Outcome: Same as current

Information By: Johns Hopkins University

Dates:
Date Received: March 9, 2017
Date Started: June 2017
Date Completion: July 2021
Last Updated: May 11, 2017
Last Verified: May 2017