Intranasal Insulin for Improving Cognitive Function in Multiple Sclerosis
Condition: Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Secondary Progressive; Multiple Sclerosis, Primary Progressive
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Chronic Progressive; Sclerosis
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This study will evaluate if giving insulin that is administered in the nostrils (intranasal)
      is safe and tolerable for people with multiple sclerosis (MS). It is also being done to
      evaluate if intranasal insulin improves cognitive function in people with MS and to evaluate
      how it might be working.
    

Detailed description: 
      Cognitive impairment is common in and devastating to people with MS. MS is a common, chronic,
      central nervous system (CNS) disease characterized by inflammation, demyelination, and
      neurodegeneration. One of the most devastating symptoms of this disease is impaired cognitive
      function, which is common and present in over 60% of individuals with MS. MS-related
      cognitive impairment is associated with lowered quality of life and reduced functional
      capacity, including loss of employment, impaired social relationships, compromised driving
      safety, and poor adherence to treatment. Impaired cognitive functioning has been observed
      early in the disease, sometimes even before diagnosis, and cognitive function has been shown
      to decline longitudinally, both over the short- and long-term. Several cognitive domains are
      impacted in people with MS, including attention, memory, executive functioning, and
      especially processing speed.

      To date, multiple pharmacologic interventions have been assessed with disappointing results.
      There was no significant difference between treatment and placebo for cognition in randomized
      control trials of donepezil, aminopyridines, gingko biloba, and memantine. Psychostimulants
      demonstrated some efficacy, but only in secondary outcome measures. Behavioral interventions
      show promise but are understudied. Furthermore, cognitive rehabilitation is often time
      consuming, costly, and not universally available. Hence, there is an urgent need to identify
      or develop novel therapies that can help improve cognitive function in MS.

      Intranasal insulin is extremely safe and tolerable in other populations, allowing for
      concentrated delivery to the nervous system. An intranasal delivery system provides a
      non-invasive way to bypass the blood-brain barrier and allow rapid delivery of a medication
      to the CNS via the olfactory and trigeminal perivascular channels.The main advantage of the
      delivery system is reducing systemic side effects via limiting a medication's exposure to
      peripheral organs and tissues.

      Insulin administration has been shown to improve memory and learning in healthy people and in
      those with neurodegenerative diseases. Intranasal insulin has been shown to have
      neuroprotective and restorative effects in several human clinical trials. Overall, findings
      suggest that intranasal insulin not only affects cognitive function acutely, but that over
      time, there may be associated structural changes that lead to a more permanent treatment
      benefit. Cognitive dysfunction is very common in MS and can be devastating, therefore a
      treatment intervention (i.e., intranasal insulin) can help both acutely and longitudinally.

      The primary aim of this study is to assess the safety and tolerability of intranasal insulin
      in people with MS. The secondary aim is to evaluate if intranasal insulin improves learning
      and memory in people with MS. The third aim is to evaluate the impact of intranasal insulin
      on measures of oxidative stress, axonal injury, cellular stress, and energy metabolism in MS.
    

Intervention name(s): Insulin; Placebo (Sterile diluent)
Intervention type(s): Drug; Drug
Intervention description(s): All patients will receive either insulin or placebo using the Vianase III N2B device during the first 24 weeks of the study.; All patients will receive either insulin or placebo using Vianase III N2B device during the first 24 weeks of the study.
Intervention MeSH terms: Insulin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment