Intranasal Insulin for the Treatment of HAND
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|ClinicalTrials.gov Identifier: NCT03081117|
Recruitment Status : Recruiting
First Posted : March 16, 2017
Last Update Posted : June 12, 2019
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 optional lumbar punctures ("spinal taps"), two MRI brain scans, monthly blood draws, and clinical assessments.
|Condition or disease||Intervention/treatment||Phase|
|HIV Dementia HIV-Associated Cognitive Motor Complex||Drug: Insulin, intranasal Drug: Placebo, intranasal||Phase 1 Phase 2|
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 studies with IMT and other neuroprotective compounds for HAND.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Randomized double-blind placebo-controlled clinical trial|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Clinical Trial of Intranasal Insulin for the Treatment of HIV-associated Neurocognitive Disorder (HAND)|
|Actual Study Start Date :||August 1, 2017|
|Estimated Primary Completion Date :||July 2021|
|Estimated Study Completion Date :||July 2021|
Experimental: Insulin, intranasal
Regular insulin, 20 IU intranasal twice a day for 24 weeks; 0.2 mL per dose
Drug: Insulin, intranasal
Regular insulin administered by specialized, non-commercial intranasal drug delivery device
Other Name: Novolin R
Placebo Comparator: Placebo, intranasal
Saline solution (placebo), intranasal twice a day for 24 weeks; 0.2 mL per dose
Drug: Placebo, intranasal
Saline solution administered by specialized, non-commercial intranasal drug delivery device
- 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
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03081117
|Contact: Ned Sacktor, MDfirstname.lastname@example.org|
|United States, Maryland|
|The Johns Hopkins Institute for Clinical and Translational Research, Adult Outpatient Clinical Research Unit||Recruiting|
|Baltimore, Maryland, United States, 21287|
|Contact: Mary De'Jarnette, RN, MSN 410-955-2760 email@example.com|
|Principal Investigator:||Ned Sacktor, MD||Johns Hopkins University|