Clinical trial NCT04251585: Intranasal Insulin in Parkinson's Disease
Official title: Single Center Safety and Tolerability Trial of Intranasal Insulin in Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson Disease
Keywords: intranasal
insulin
Lead sponsor: HealthPartners Institute
Sponsor class: OTHER
First posted: 2020-02-05
Enrollment: 31
Sex: ALL
Minimum age (years): 41
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomly assigned to one of 3 treatment groups or the placebo group.

* 20 international units twice daily (n=7)
* 40 international units twice daily (n=7)
* 80 international units twice daily (n=9)
* placebo (n=7)
Primary purpose: OTHER

Brief summary: This project will investigate exploratory outcomes related to the effect of intranasal insulin on cognition, mood, apathy and motor performance of subjects with Parkinson's disease over a 3 week period.

Detailed description: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's dementia and was originally described as a motor disease. The diagnosis of PD is still based on the core motor features of bradykinesia, resting tremor, and rigidity, primarily as a result of degeneration of nigrostriatal dopaminergic neurons. In addition to the classic motor symptoms, however, PD is increasingly recognized as a multisystem disorder. A variety of non-motor symptoms, including cognitive deficits and dementia, are commonly observed in patients with PD.

In this study, we aim to investigate which intranasal insulin dose out of three doses and placebo, administered at three different doses or placebo over a 21-day period, is the optimum dosage based on safety and tolerability in Parkinson's disease. A similar design was used in a trial investigating intranasal oxytocin in frontotemporal dementia. Dosing for the first two groups of this study is based on previously conducted intranasal insulin studies in Alzheimer's disease (AD) and mild cognitive impairment (MCI), using daily doses on 20 and 40 IU of intranasal insulin. Higher dose have been found to be safe in healthy adults. Prior studies performed have demonstrated favorable effects of this regimen in the MCI/AD population without peripheral hypoglycemia.

Eligibility criteria: Inclusion Criteria:

* Subject has Idiopathic PD defined by the cardinal sign, bradykinesia, plus the presence of at least 1 of the following: resting tremor or rigidity and without any other known or suspected cause of Parkinsonism (according to Movement disorder society (MDS) clinical diagnostic criteria for Parkinson's disease confirmed by a fellowship trained movements disorder specialist
* Subject is Hoehn \& Yahr stage less than or equal to 3
* Subject has a MOCA score ≥10.
* Subject is \> 40 and \<90 years of age.
* Female subjects are post-menopausal or have a negative pregnancy test
* The subject must be proficient in speaking, reading and understanding English in order to comply with procedural testing of cognitive function, memory and physiology.
* Subject has provided informed written consent prior to participation. In the event that subject is legally unable to provide informed written consent due to deterioration in cognitive abilities, fully informed written consent must be provided by a legally authorized representative.
* Subject is on a stable dose (at least 1 month prior to baseline visit) of antiparkinsonian agents and is willing to remain on this dose for the duration of the study. If the subject is on a cholinesterase inhibitor, a stable dose without changes for 1 month is also required.
* Subject has undergone a brain CT or MRI prior to the study as part of their previous diagnostic workup for PD to rule out underlying structural lesions, as determined clinically significant by the investigator

Exclusion Criteria:

* Subject has atypical Parkinson's syndrome(s) due to drugs (e.g., metoclopramide, neuroleptics), metabolic neurogenetic disorders (e.g., Wilson's Disease), encephalitis, cerebrovascular disease, or degenerative disease (e.g., Progressive Supranuclear Palsy, Multiple System Atrophy, Corticobasal Degeneration, Lewy Body dementia)
* Subject has medical history and/or clinically determined disorders: chronic sinusitis, untreated thyroid disease, or significant head trauma.
* Subject has history of any of the following: moderate to severe pulmonary disease, poorly controlled congestive heart failure, significant cardiovascular and/or cerebrovascular events within previous 6 months, condition known to affect absorption, distribution, metabolism, or excretion of drugs such as any hepatic, renal or gastrointestinal disease or any other clinically relevant abnormality that inclusion would pose a safety risk to the subject as determined by investigator.
* Subject has had previous nasal and/or oto-pharyngeal surgery and severe deviated septum and/or other anomalies.
* Subject has history of any psychiatric illness that would pose a safety risk to the subject as determined by investigator.
* Subject is currently taking sedative medications that are clinically contraindicated as determined by investigator.
* Subject has undergone a recent change (\<1 month) in their anti-parkinsonian medication, cholinesterase inhibitor or anti-depressant medication.
* Subject has current or recent drug or alcohol abuse or dependence as defined by Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV TR).
* Screening laboratory results that are medically relevant, in which inclusion would pose a safety risk to the subject as determined by investigator.
* Subject has participated in a clinical trial investigation within 3 months of this study.
* Subject has an insulin allergy.
* Subject has Insulin-dependent diabetes

Primary outcomes:
measure: Safety measured by count of safety events
timeFrame: 3 weeks
measure: Safety measured by fasting glucose
timeFrame: 3 weeks
measure: Safety measured by body weight
timeFrame: 3 weeks
measure: Safety measured by the number of serious adverse events (SAE) and adverse events (AE)
timeFrame: 3 weeks
Secondary outcomes:
measure: Cognitive function measured by the Montreal cognitive assessment (MoCA)
timeFrame: 5 weeks
measure: Cognitive function measured by the Weschler Adult Intelligence Scale - Fourth Edition (WAIS-IV) Digit Span
timeFrame: 3 weeks
measure: Cognitive function measured by the Trailmaking Test Part A Time
timeFrame: 3 weeks
measure: Cognitive function measured by the Trailmaking Test Part B Time
timeFrame: 3 weeks
measure: Cognitive function measured by the Trailmaking Test Parts A & B Errors
timeFrame: 3 weeks
measure: Cognitive function measured by the Judgement of Line Orientation
timeFrame: 3 weeks
measure: Cognitive function measured by the Logical Memory Scaled Scores
timeFrame: 3 weeks
measure: Cognitive function measured by the Logical Memory Recognition
timeFrame: 3 weeks
measure: Cognitive function measured by the Hopkins Verbal Learning Test - Revised (HVLT)
timeFrame: 3 weeks
measure: Cognitive function measured by the Visuospatial Memory Test - Revised (BVMT)
timeFrame: 3 weeks
measure: Cognitive function measured by the Stroop Color Word Test (CWT)
timeFrame: 3 weeks
measure: Cognitive function measured by Fluency
timeFrame: 3 weeks
measure: Mood measured by the Beck Depression Inventory - Second Edition
timeFrame: 3 weeks
measure: Apathy measured by the Apathy scale
timeFrame: 3 weeks
measure: Mood measured by the Columbia Suicide Severity Rating (C-SSRS)
timeFrame: 3 weeks
measure: Motor function as measured by the United Parkinson's Disease Rating Scale (UPDRS)
timeFrame: 3 weeks
Other outcomes:
Locations:
city: Saint Paul
country: United States
facility: HealthPartners Neuroscience Center
state: Minnesota
Study officials:
affiliation: HealthPartners Neurology
name: Julia C Johnson, MD
role: PRINCIPAL_INVESTIGATOR
References: