Intranasal Insulin for the Treatment of HAND

NCT03081117 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: IRB00108564
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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 optional lumbar punctures ("spinal taps"), two MRI brain scans, monthly blood draws, and clinical assessments.

Conditions

HIV Dementia; HIV-Associated Cognitive Motor Complex

Keywords

HIV-Associated Neurocognitive Disorder (HAND); Intranasal

Outcome Measures

Primary Outcomes (3)

• Serious Adverse Event Frequency

  Number of documented serious adverse events per participant, mean

  Total during 24-week trial

• Serious Adverse Event Frequency, Participant Count

  Number participants with at least one documented serious adverse event, count

  Total during 24-week trial

• Neurocognitive Performance: Global Deficit Score (GDS), Week 24 Visit Score Minus Baseline Score

  Change in GDS, measured at two time points, baseline and Week 24 visits. GDS is a composite score based on neurocognitive test performance. The 14 data points that comprise the GDS include Hopkins Verbal Learning Test (trials 1-3 total score and delayed recall), Rey Complex Figure Test (copy and delayed recall), WAIS symbol-digit test, grooved pegboard (dominant and non-dominant), CalCAP (Choice reaction time and Sequential reaction time), Trail-making Test (Parts A and B), Stroop Color Interference Test (trial 3), timed gait (3 trials average), and verbal fluency (FAS). Raw scores were transformed to t-scores using age/education stratified normative data, then assigned a discrete value from 0 to 5 using the following t-score categorization: \> or = 40 is '0', 35.00 to 39.99 is '1', 30.00 to 34.99 is '2', 25.00 to 29.99 is '3', 20.00 to 24.99 is '4', and \<20 is '5'. The 14 individual scores were then averaged. A higher GDS is a worse outcome (0 = no deficits and 5 = maximum deficits).

  Difference between baseline and week 24 visits

Secondary Outcomes (11)

• Neurocognitive Performance: NPZ-8 Score, Week 24 Visit Score Minus Baseline Score

  Difference between baseline and week 24 visits

• CSF Biomarkers, Week 24 Visit Value Minus Baseline Value

  Between baseline and week 24 visits

• Neuroimaging Markers: SV-MRS, Myoinositol, Basal Ganglia, Week 24 Visit Value Minus Baseline Value

  Changes between baseline and week 24 visits

• Neuroimaging Markers: SV-MRS, Myoinositol, Frontal White Matter, Week 24 Visit Value Minus Baseline Value

  Changes between baseline and week 24 visits

• Neuroimaging Markers: SV-MRS, Choline, Basal Ganglia, Week 24 Visit Value Minus Baseline Value

  Changes between baseline and week 24 visits

Study Arms (2)

Insulin, intranasal

EXPERIMENTAL

Regular insulin, 20 IU intranasal twice a day for 24 weeks; 0.2 mL per dose

Drug: Insulin, intranasal

Placebo, intranasal

PLACEBO COMPARATOR

Saline solution (placebo), intranasal twice a day for 24 weeks; 0.2 mL per dose

Drug: Placebo, intranasal

Interventions

Insulin, intranasal DRUG

Regular insulin administered by specialized, non-commercial intranasal drug delivery device

Also known as: Novolin R

Insulin, intranasal

Placebo, intranasal DRUG

Saline solution administered by specialized, non-commercial intranasal drug delivery device

Placebo, intranasal

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have HIV,
• Capable of providing informed consent,
• Between the ages of 18-69 years,
• Evidence of problems with memory, speed, and brain function,
• Same HIV medications for at least 6 months (180 days) prior to study entry, with no plans to change the medications over the study period,
• The following blood lab values within 2 weeks prior to study entry: hemoglobin \> 8.9 g/dl, absolute neutrophil count \> 500 cells/mm3, platelet count \> 50,000 cells/mm3, alanine aminotransferase (ALT) \< 2.5 X upper limit of normal, alkaline phosphatase \< 3 X upper limit of normal, serum creatinine ≤ 2 X upper limit of normal,
• Negative pregnancy test (for women who could become pregnant),
• Able and willing to use an intranasal device for taking the study drug without complications (e.g., no history of traumatic obstruction to nasal passage, chronic sinus infections, severe and symptomatic seasonal allergies, etc.),
• Currently suppressed blood HIV viral load (undetectable or \<400 copies/mL).

You may not qualify if:

• Current or past opportunistic infection of the brain,
• History or current clinical evidence of schizophrenia,
• History of chronic neurological disorder, such as multiple sclerosis or uncontrolled epilepsy,
• Active symptomatic AIDS defining opportunistic infection within 30 days prior to study entry,
• History of an uncontrolled medical or psychiatric illness which in the opinion of the investigators would constitute a safety risk for patients or interfere with the ability of a participant to complete the study,
• History of diabetes or treatment with insulin or an oral hypoglycemic agent,
• Amylase/lipase elevation (≥ 2 X upper limit of normal) within 14 days prior to starting study drug,
• Detectable plasma HIV RNA test ≥400 copies/mL within 6 months prior to baseline/randomization,
• History of any endocrine related cancer, including any thyroid tumor,
• Current use of cocaine, heroin, or methamphetamine. Current use will be defined and determined by any evidence of such use within the two years (730 days) prior to study enrollment; evidence includes but is not limited to urine drug toxicology testing by the study team at screening and pre-entry visits,
• Presence of other conditions that significantly affect and complicate performance on neurocognitive tests (such as, learning disabilities, history of severe alcohol abuse, head injury with trauma to the brain and loss of consciousness \>30 minutes).

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

The Johns Hopkins Institute for Clinical and Translational Research, Adult Outpatient Clinical Research Unit

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

AIDS Dementia Complex

Interventions

Insulin

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr. Leah Rubin, Associate Professor of Neurology, Psychiatry, and Epidemiology
• Organization: Johns Hopkins University

lrubin@jhu.edu

410-955-7311

Study Officials

• Leah Rubin, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized double-blind placebo-controlled clinical trial

Study Record Dates

• First Submitted: March 9, 2017
• First Posted: March 16, 2017
• Study Start: August 1, 2017
• Primary Completion: May 20, 2020
• Study Completion: October 16, 2020
• Last Updated: July 7, 2021
• Results First Posted: July 7, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)