Clinical trial NCT02988401: Intranasal Insulin for Improving Cognitive Function in Multiple Sclerosis
Official title: Intranasal Insulin for Improving Cognitive Function in Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Sclerosis, Relapsing-Remitting
Multiple Sclerosis, Secondary Progressive
Multiple Sclerosis, Primary Progressive
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2016-12-09
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Cognitive Function as Assessed by the Symbol Digit Modalities Test (SDMT)
timeFrame: Up to week 24 visit
Secondary outcomes:
measure: Number of Participants With Adverse Events Leading to Study Discontinuation
timeFrame: Up to week 24 visit
measure: Fingerstick Blood Glucose (Subset)
timeFrame: At the baseline visit, monitored twice within the 90 minutes following the first dose administration of study drug
measure: Change From Baseline in Cognitive Function as Assessed by the Controlled Oral Word Association Test (COWAT)
timeFrame: Up to week 24 visit
measure: Change From Baseline in Cognitive Function as Assessed by the California Verbal Learning Test, Second Edition (CVLT-II)
timeFrame: Up to week 24 visit
measure: Change From Baseline in Cognitive Function as Assessed by the Brief Visuospatial Memory Test - Revised (BVMT-R) Delayed Recall
timeFrame: Up to week 24 visit
measure: Change in Cognitive Function as Assessed by the Rao-version of the Paced Auditory Serial Addition Test (PASAT)
timeFrame: Up to week 24 visit
measure: Change From Baseline in Cognitive Function as Assessed by the Judgement of Line Orientation Test (JLO)
timeFrame: Up to week 24 visit
measure: Change From Baseline in Cognitive Function as Assessed by the Delis-Kaplan Executive Function System Sorting Test
timeFrame: Up to week 24 visit
Other outcomes:
measure: Assess Depression Severity, as Measured by the Beck Depression Inventory-II (BDI-II)
timeFrame: Up to week 24 visit
measure: Evaluation of Impact of Study Products on Health Related Quality of Life Using the Functional Assessment of Multiple Sclerosis Questionnaire (FAMS)
timeFrame: Up to week 24 visit
measure: Evaluation of How Overall Sleep Quality Impacts People With MS Using a Sleep Questionnaire (Pittsburgh Sleep Quality Index)
timeFrame: Up to week 24 visit
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Ellen Mowry, MD, MCR
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Scott Newsome, DO
role: PRINCIPAL_INVESTIGATOR
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