Safety Study of Intranasal Insulin in Type 1 Diabetes and Diabetic Peripheral Neuropathy
Condition: Diabetic Peripheral Neuropathy
MeSH terms: Peripheral Nervous System Diseases; Diabetic Neuropathies
Study type: Interventional
Phase: Phase 2

Summary: 
      The aim of this study is to evaluate the safety and tolerability of intranasal insulin in
      people with type 1 diabetes and diabetic peripheral neuropathy and to determine whether
      intranasal insulin is effective in slowing the progression of diabetic neuropathy.
    

Detailed description: 
      Diabetic polyneuropathy (DPN) is a common complication of human type I and II diabetes
      mellitus, identified in up to 50% of diabetic subjects regardless of age or type of diabetes.
      As the global burden of diabetes heightens due to an epidemic of type II diabetes, the
      prevalence of DPN will concurrently rise. Clinical features of DPN include loss of sensation,
      propensity towards traumatic wound formation, neuropathic pain, motor weakness and falls.

      At this time there is no specific therapy to arrest or reverse DPN. Previous work has
      demonstrated not only an absolute reduction in plasma insulin levels in Type I diabetes but
      also in type II diabetics. At the present, therapy for neuropathic pain associated with DPN
      is available, but only targets symptom relief and is only partially effective.

      Intranasal insulin administration is a novel approach to the treatment of diabetic
      polyneuropathy (DPN) based on robust basic science research. Intranasal insulin is currently
      being studied in other conditions and has completed Phase II in subjects with cognitive
      impairment and mild Alzheimer's disease. Intranasal administration of insulin results in
      increased penetration into the cerebrospinal fluid and the peripheral nervous system while
      avoiding systemic absorption. Lack of systemic absorption results in maintenance of normal
      blood glucose levels in normal healthy subjects.

      The objectives of the current study are as follows:

        1. Primary: To determine the safety and tolerability of intranasal insulin delivery in
           subjects with type 1 diabetes and DPN.

        2. Secondary: To determine whether intranasal insulin is efficacious in slowing the
           progression of DPN.

      This study is designed as a double-blind, placebo-controlled, randomized, controlled-dose
      escalation phase 2 pilot clinical trial.

      The duration of the study for each subject is 11 weeks with 6 weeks of blinded study
      treatment. The study treatment is either active study drug (Novolin Toronto insulin) or
      placebo (normal saline).

      The phases of the study are as follows:

        1. Screening phase (3 weeks): Potential subjects undergo screening procedures to determine
           eligibility. Procedures include informed consent, review of medical history,
           anthropometric measures, vital signs, physical examination (including a neurological
           assessment), and bloodwork.

        2. Baseline phase (2 weeks): Eligibility of subjects is confirmed and subjects commence
           collection of protocol-specified blood glucoses on a daily basis. Nerve conduction tests
           and corneal confocal microscopy is completed prior to the start of the next phase.

        3. Treatment phase (6 weeks): Subjects commence the study treatment at the lowest
           protocol-specified dose. If assigned to Novolin Toronto insulin, this is 20
           international units (IU) twice daily (BID). Return visits to the clinic occur every two
           weeks for dose escalation. The dose increase is 40 IU BID, then 80 IU BID. Subjects
           assigned to normal saline receive a volume equivalent to the total volume given to the
           subjects taking insulin. Visits during the treatment phase also include safety
           bloodwork, serial blood glucose measurements every 15 minutes for a 2 hour period,
           review of any hypoglycemia, adverse events, changes to concomitant medications,
           assessment of neuropathy, questionnaires, teaching, and study treatment
           accountability/compliance assessment. The study completes at the 11 week time period,
           immediately prior to which the second nerve conduction study and corneal confocal
           microscopy is completed.

      The study protocol is designed to monitor hypoglycemia throughout the baseline and treatment
      period for all subjects. Any severe hypoglycemia or significant increases in hypoglycemia
      (>30% compared to the baseline phase) will be reviewed by the Investigator on a case-by-case
      basis to determine continuation with study treatment. Any subject that undergoes
      discontinuation of study treatment will be continued to be followed to 11 weeks (without
      study treatment).
    

Intervention name(s): Novolin Toronto insulin; Normal saline
Intervention type(s): Drug; Drug
Intervention description(s): Subjects randomized to active drug are provided with 20 IU BID of Novolin Toronto at randomization (week 5). The dosing is prescribed to be taken 30 minutes after the morning meal (breakfast) and 30 minutes after the evening meal (supper). Subjects are asked to consume their meals and take their doses of study treatment within the same time frame each day. Dose escalations occur every 2 weeks with the insulin increasing to 40 IU BID at week 7, then 80 IU BID at week 9. The study completes at week 11. The total treatment period is 6 weeks. The insulin is diluted with an amount of normal saline to provide a total volume in the study treatment vial to equal 1.1 milliliters.; Subjects randomized to placebo are provided with 1.1 milliliters of normal saline at randomization (week 5). The study completes at week 11. The total treatment period is 6 weeks. The dosing is prescribed to be taken 30 minutes after the morning meal (breakfast)and 30 minutes after the evening meal (supper). Subjects are asked to consume their meals and take their doses of study treatment within the same time frame each day. The amount of normal saline in the study treatment vial (1.1 milliliters) is identical in volume to the active insulin being used in the study .
Intervention MeSH terms: Insulin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: Insulin; Diabetic neuropathy; Intranasal administration; Pilot project