Single Center Safety and Tolerability Trial of Intranasal Insulin in Parkinson's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Safety Measured by Count of Safety Events
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
All participants, care providers, investigators, and outcomes assessors are masked.
入排标准
- 年龄范围
- 41 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 ≥
- •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
排除标准
- •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
研究组 & 干预措施
Low Insulin
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
干预措施: Regular Novolin R (Drug)
Medium Insulin
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
干预措施: Regular Novolin R (Drug)
High Insulin
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
干预措施: Regular Novolin R (Drug)
Placebo
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
干预措施: Placebo (Drug)
结局指标
主要结局
Safety Measured by Count of Safety Events
时间窗: 3 weeks
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.
Safety Measured by Fasting Glucose
时间窗: baseline and 3 weeks
Pre-post change in fasting glucose (mg/dL). A larger decrease in fasting glucose indicates a less safe treatment.
Safety Measured by Body Weight
时间窗: baseline and 3 weeks
Pre-post change in body weight (lbs). An unintended decrease in body weight indicates a less safe treatment.
Safety Measured by the Number of Serious Adverse Events (SAE) and Adverse Events (AE)
时间窗: 3 weeks
Total number of AEs/SAEs during the course of treatment. More AEs/SAEs indicates a less safe treatment.
次要结局
- Cognitive Function Measured by the Montreal Cognitive Assessment (MoCA)(5 weeks)
- Cognitive Function Measured by the Weschler Adult Intelligence Scale - Fourth Edition (WAIS-IV) Digit Span(3 weeks)
- Mood Measured by the Beck Depression Inventory - Second Edition(baseline and 3 weeks)
- Apathy Measured by the Apathy Scale(baseline and 3 weeks)
- Mood Measured by the Columbia Suicide Severity Rating (C-SSRS)(baseline and 3 weeks)
- Motor Function as Measured by the United Parkinson's Disease Rating Scale (UPDRS-III)(baseline and 3 weeks)
- Cognitive Function Measured by the Trailmaking Test Part A Time(baseline and 3 weeks)
- Cognitive Function Measured by the Trailmaking Test Part B Time(baseline and 3 weeks)
- Cognitive Function Measured by the Trailmaking Test Parts A & B Errors(3 weeks)
- Cognitive Function Measured by the Judgement of Line Orientation(baseline and 3 weeks)
- Cognitive Function Measured by the Logical Memory Scaled Scores(baseline and 3 weeks)
- Cognitive Function Measured by the Logical Memory, Recognition(baseline and 3 weeks)
- Cognitive Function Measured by the Hopkins Verbal Learning Test - Revised (HVLT)(baseline and 3 weeks)
- Cognitive Function Measured by the Visuospatial Memory Test - Revised (BVMT)(3 weeks)
- Cognitive Function Measured by the Stroop Color Word Test (CWT)(baseline and 3 weeks)
- Cognitive Function Measured by Fluency(baseline and 3 weeks)
- Cognitive Function Measured by Visuospatial Memory Test - Revised (BVMT Recognition)(baseline and 3 weeks)