Intranasal Insulin for Improving Cognitive Function in Multiple Sclerosis

Johns Hopkins University

Status and phase: Completed; Phase 2; Phase 1

Conditions: Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Secondary Progressive; Multiple Sclerosis, Primary Progressive

Treatments: Drug: Insulin; Drug: Placebo (Sterile diluent)

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT02988401

IRB00095554

Details and patient eligibility

About

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.

Full 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.

Enrollment: 105 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Meets 2010 criteria for MS
• No relapse in past 3 months
• At least mild cognitive impairment (based off of SDMT/PST score)
• Capacity to learn and self-administer intranasal insulin/placebo, or presence of a caregiver with such capacity who is willing to do it for the duration of the trial
• Untreated/on the same MS therapy for at least 6 months, with no anticipated change in the next year
• Willing to prevent pregnancy during study if female of childbearing potential

Exclusion criteria

• Current, active major depression
• No tricyclic antidepressant or anticonvulsant (except carbamazepine, pregabalin or gabapentin) use within 6 weeks of screening; if on oxybutynin or tolterodine, on stable dose for > 6 months without plans for changing dose in next year
• If taking selective serotonin (± norepinephrine) reuptake inhibitors, pregabalin, gabapentin, sympathomimetic, monoamine oxidase inhibitor, antipsychotic, amantadine, cholinesterase inhibitor, memantine, modafanil, armodafinil, or evening short-acting benzodiazepines, on stable dose for 6 weeks or greater
• Pregnant or nursing
• THC; illicit drug or alcohol abuse in past 3 months
• History of diabetes mellitus or insulin resistance
• Active liver disease, stage IV/V kidney disease or severe metabolic derangements
• CNS disorder other than MS or headache

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

105 participants in 3 patient groups, including a placebo group

Intranasal insulin 20 international units

Experimental group

Description:

Subjects will administer 20 I.U. of insulin in the nostrils using a ViaNaseTM controlled particle dispersion nasal device two times/day (BID) for 24 weeks.

Treatment:

Drug: Insulin

Intranasal insulin 10 international units

Experimental group

Description:

Subjects will administer 10 I.U. of insulin in the nostrils using a ViaNaseTM controlled particle dispersion nasal device two times/day (BID) for 24 weeks.

Treatment:

Drug: Insulin

Intranasal saline

Placebo Comparator group

Description:

Subjects will administer a sterile diluent containing inactive ingredients in the nostrils using a ViaNaseTM controlled particle dispersion nasal device two times/day (BID) for 24 weeks.

Treatment:

Drug: Placebo (Sterile diluent)