Intranasal Insulin in Parkinson's Disease (INI-PD)

Single Center Safety and Tolerability Trial of Intranasal Insulin in Parkinson's Disease

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.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Regular Novolin R; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sharon Hwee; Phone Number: 651-495-6363; Email: Sharon.x.Hwee@HealthPartners.com
• Study Contact Backup: Name: Maria Pyle; Phone Number: 651-495-6363; Email: Maria.X.Pyle@HealthPartners.com

Study Locations

• United States
  • Minnesota
    • Saint Paul, Minnesota, United States, 55130
      • Recruiting
      • HealthPartners Neuroscience Center
      • Contact: Sharon Hwee; Phone Number: 651-495-6363; Email: Sharon.x.Hwee@HealthPartners.com
      • Contact: Maria Pyle; Phone Number: 651-495-6363; Email: Maria.X.Pyle@HealthPartners.com
      • Principal Investigator: Julia C Johnson, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 41 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Insulin; Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.	Drug: Regular Novolin R; Intranasal insulin
Experimental: Medium Insulin; Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.	Drug: Regular Novolin R; Intranasal insulin
Experimental: High Insulin; Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.	Drug: Regular Novolin R; Intranasal insulin
Placebo Comparator: Placebo; 0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.	Drug: Placebo; Intranasal placebo (0.9% saline)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety measured by count of safety events	Composite safety event - this is a count of either a reduction of fasting glucose to <70 mg/dL or an unintended reduction of weight >5%. A larger composite event count indicates a less safe treatment.	3 weeks
Safety measured by fasting glucose	Pre-post change in fasting glucose (mg/dL). A larger decrease in fasting glucose indicates a less safe treatment.	3 weeks
Safety measured by body weight	Pre-post change in body weight (lbs). An unintended decrease in body weight indicates a less safe treatment.	3 weeks
Safety measured by the number of serious adverse events (SAE) and adverse events (AE)	Total number of AEs/SAEs during the course of treatment. More AEs/SAEs indicates a less safe treatment.	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive function measured by the Montreal cognitive assessment (MoCA)	Pre-post difference. Total sum of scores. Range: 0-30. Higher score indicates less memory loss	5 weeks
Cognitive function measured by the Weschler Adult Intelligence Scale - Fourth Edition (WAIS-IV) Digit Span	Pre-post difference. Scaled score. Range: 1-19. Forward and backward. Lower score indicates more impairment.	3 weeks
Cognitive function measured by the Trailmaking Test Part A Time	Pre-post difference. T-score. Range: 0-25. Lower score indicates more impairment.	3 weeks
Cognitive function measured by the Trailmaking Test Part B Time	Pre-post difference. T-score. Range: 0-26. Lower score indicates more impairment.	3 weeks
Cognitive function measured by the Trailmaking Test Parts A & B Errors	Pre-post difference. Total number of errors. No range. More errors indicate more impairment.	3 weeks
Cognitive function measured by the Judgement of Line Orientation	Pre-post difference. Z-score. Range: 0-29. Lower score indicates more impairment.	3 weeks
Cognitive function measured by the Logical Memory Scaled Scores	Pre-post difference. Scaled score. Range: 1-19. Logical memory immediate, delayed and recognition. Lower score indicates more impairment.	3 weeks
Cognitive function measured by the Logical Memory Recognition	Pre-post difference. No range. Lower score indicates more impairment.	3 weeks
Cognitive function measured by the Hopkins Verbal Learning Test - Revised (HVLT)	Pre-post difference. T-score. Range: 0-12. Immediate recall, delayed recall, and recognition. Lower score indicates more impairment.	3 weeks
Cognitive function measured by the Visuospatial Memory Test - Revised (BVMT)	Pre-post difference. T-score. Range: 0-6. Immediate recall, delayed recall, and recognition. Lower score indicates more impairment.	3 weeks
Cognitive function measured by the Stroop Color Word Test (CWT)	Pre-post difference. T-score. Range: 0-25. Word reading, color naming, color-word, and interference. Lower score indicates more impairment.	3 weeks
Cognitive function measured by Fluency	Pre-post difference. T-score. No range. Letter fluency and category fluency. Lower score indicates more impairment.	3 weeks
Mood measured by the Beck Depression Inventory - Second Edition	Pre-post difference. Raw score. Range: 0-63. Higher score indicates more symptomatic.	3 weeks
Apathy measured by the Apathy scale	Pre-post difference. Raw score. Range: 0-42. Higher score indicates more symptomatic.	3 weeks
Mood measured by the Columbia Suicide Severity Rating (C-SSRS)	Pre-post difference. Raw score. Range:1 or 0. 1 score - more symptomatic, 0 score - no symptoms.	3 weeks
Motor function as measured by the United Parkinson's Disease Rating Scale (UPDRS)	Pre-post difference. Raw score. Range: 0-72. Higher score indicates more symptomatic.	3 weeks

Collaborators and Investigators

• Sponsor: HealthPartners Institute
• Investigators: Principal Investigator: Julia C Johnson, MD, HealthPartners Neurology

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2020
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: January 28, 2020
• First Submitted That Met QC Criteria: January 29, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: intranasal; insulin
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: A19-214

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No