A Phase IIa Dose Escalation Pilot Study to Investigate the Safety and Tolerability of Intranasal Insulin in Subjects With Diabetic Polyneuropathy.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Hypoglycemia monitoring
研究概览
简要总结
The aim of this study is to evaluate the safety and tolerability of intranasal insulin in people with type 1 diabetes and diabetic peripheral neuropathy and to determine whether intranasal insulin is effective in slowing the progression of diabetic neuropathy.
详细描述
Diabetic polyneuropathy (DPN) is a common complication of human type I and II diabetes mellitus, identified in up to 50% of diabetic subjects regardless of age or type of diabetes. As the global burden of diabetes heightens due to an epidemic of type II diabetes, the prevalence of DPN will concurrently rise. Clinical features of DPN include loss of sensation, propensity towards traumatic wound formation, neuropathic pain, motor weakness and falls.
At this time there is no specific therapy to arrest or reverse DPN. Previous work has demonstrated not only an absolute reduction in plasma insulin levels in Type I diabetes but also in type II diabetics. At the present, therapy for neuropathic pain associated with DPN is available, but only targets symptom relief and is only partially effective.
Intranasal insulin administration is a novel approach to the treatment of diabetic polyneuropathy (DPN) based on robust basic science research. Intranasal insulin is currently being studied in other conditions and has completed Phase II in subjects with cognitive impairment and mild Alzheimer's disease. Intranasal administration of insulin results in increased penetration into the cerebrospinal fluid and the peripheral nervous system while avoiding systemic absorption. Lack of systemic absorption results in maintenance of normal blood glucose levels in normal healthy subjects.
The objectives of the current study are as follows:
- Primary: To determine the safety and tolerability of intranasal insulin delivery in subjects with type 1 diabetes and DPN.
- Secondary: To determine whether intranasal insulin is efficacious in slowing the progression of DPN.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients classified as having type 1 diabetes mellitus according to the Canadian Diabetes Association Criteria.
- •Patients clinically defined as having DPN, meeting at least two of the following conditions:
- •clinical signs of polyneuropathy;
- •Symptoms of nerve dysfunction;
- •Nerve conduction deficits in at least 2 nerves.
- •Aged 18 through 70 years (inclusive).
- •Body Mass Index (BMI) <30 kilograms/meter2.
排除标准
- •Any other possible etiology contributing to the neuropathy:
- •History of prolonged untreated hypothyroidism.
- •Presence of untreated B12 deficiency.
- •Presence of a paraproteinemia, detected using serum protein electrophoresis with a minimal threshold detection of 2 g/L.
- •Use of a neurotoxic medication with a clear association with peripheral neuropathy within the past 1 year based upon clinical impression of association.
- •Previous exposure chemotherapeutic agents with a clear association with peripheral neuropathy at any time.
- •History of 2 or more severe hypoglycemic episodes within the previous 6 months.
- •History of clustering of hypoglycemia episodes within the previous 12 months.
- •History of active or recent (<5 years) malignancy.
- •History of systemic or local nasal disease that would complicate the use of intranasal insulin.
- •Presence of diabetic nephropathy requiring dialysis.
- •Presence of active proliferative retinopathy requiring surgery within 6 months.
- •Pregnancy or lactation (female subject of reproductive age must be on contraception).
- •Active cardiovascular disease:
- •Recent angina (<5 years)
- •Recent myocardial infarction (<5 years)
- •Congestive heart failure
- •Active psychiatric disorder or previous history of psychosis.
- •Unable to understand or provide consent.
- •Previously documented hypersensitivity to insulin.
- •History of hypoglycemia unawareness.
- •Glycated hemoglobin < 7.0%.
- •Ongoing involvement in another investigational drug trial.
研究组 & 干预措施
Novolin Toronto insulin
干预措施: Novolin Toronto insulin (Drug)
Normal saline
干预措施: Normal saline (Drug)
结局指标
主要结局
Hypoglycemia monitoring
时间窗: 8 weeks
Hypoglycemia is defined by the development of autonomic or neuroglycopenic symptoms, and with or without the presence of a blood glucose measurement. All qualifying subjects are provided with blood glucose testing supplies to monitor blood glucoses six times daily from week 3 to week 11 of the study. Any severe hypoglycemia or increase of hypoglycemia of greater than 30% from the baseline phase (week 3 to week 5) is deemed clinically significant and is reviewed by the investigator to determine subject continuation with study treatment.
次要结局
- Treatment satisfaction questionnaire for medication (TSQM)(6 weeks)
- Electrophysiology(6 weeks)
- Adverse effects(11 weeks)
- The UTAH early neuropathy scale(6 weeks)
- Corneal confocal microscopy(6 weeks)
- McGill pain questionnaire(6 weeks)
- Short Form-36 (SF-36) Quality of life scale(6 weeks)
研究者
DR. LAWRENCE KORNGUT
Medical Doctor, Neurologist
University of Calgary