Pharmacodynamic Evaluation of ZT-01 in a Stepped Hypoglycemic Clamp Model in Subjects With Type 1 Diabetes Mellitus
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Change in glucagon between euglycemia and hypoglycemia
研究概览
简要总结
The purpose of this study is to determine whether ZT-01 increases the glucagon response to hypoglycemia in type 1 diabetes (T1D). ZT-01 is a specific somatostatin (SST) type 2 receptor antagonist hypothesized to increase the counterregulatory glucagon release during hypoglycemia, which is impaired in diabetes, and may thus reduce the occurrence of hypoglycemia.
Approximately 25 participants with well-controlled type 1 diabetes will be recruited to a crossover study and be randomized to the order in which they receive a single administration of placebo, low dose and high dose ZT-01 during three euglycemic-hypoglycemic clamps 2 to 6 weeks apart, with a follow-up visit approximately 1 week after the final clamp.
Participants will stay overnight in the clinic before each clamp, and their plasma glucose (PG) will be kept at euglycemic levels with IV insulin and dextrose as needed. The following morning, the clamp will begin and the subject's PG will be kept at 5.5 mmol/L (euglycemia) with variable IV insulin (and dextrose as needed). Study treatment will be administered during this euglycemic period, and then insulin will be increased so that PG falls to a plateau of mild hypoglycemia, and then increased further to clinically significant hypoglycemia. Release of glucagon and other counterregulatory hormones will be measured, and a symptom score will be completed, during euglycemia before and following study treatment, and during each level of hypoglycemia. Following the clamp, the participant's blood glucose will be returned to normal levels prior to leaving the clinic.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
The participant, the investigator and site staff conducting all study procedures are masked to treatment administered at each clamp.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 1 diabetes for at least 5 years and receiving insulin as the only T1D therapy
- •HbA1c ≥6.0 and ≤9.0 %
- •BMI ≥18 to ≤27 kg/m^2
- •Normal thyroid function
排除标准
- •Impaired hypoglycemia awareness
- •Severe hypoglycemia or diabetic ketoacidosis (DKA) within 3 months
- •Abnormal blood pressure or ECG, clinically significant cardiovascular, cerebrovascular or peripheral vascular disease
- •History of pheochromocytoma, insulinoma, glucagonoma, acromegaly, Cushing's disease, glycogen storage disease or adrenal insufficiency; ongoing or previous treatment with octreotide, lanreotide or pasireotide
- •Current use of systemic corticosteroids or beta-blockers
研究组 & 干预措施
Treatment order: placebo, low dose, high dose
Subjects will receive a single administration of each treatment in this order during three consecutive clamps
干预措施: ZT-01 low dose (Drug)
Treatment order: placebo, low dose, high dose
Subjects will receive a single administration of each treatment in this order during three consecutive clamps
干预措施: ZT-01 high dose (Drug)
Treatment order: placebo, low dose, high dose
Subjects will receive a single administration of each treatment in this order during three consecutive clamps
干预措施: Placebo (Drug)
Treatment order: placebo, high dose, low dose
Subjects will receive a single administration of each treatment in this order during three consecutive clamps
干预措施: ZT-01 low dose (Drug)
Treatment order: placebo, high dose, low dose
Subjects will receive a single administration of each treatment in this order during three consecutive clamps
干预措施: ZT-01 high dose (Drug)
Treatment order: placebo, high dose, low dose
Subjects will receive a single administration of each treatment in this order during three consecutive clamps
干预措施: Placebo (Drug)
Treatment order: low dose, placebo, high dose
Subjects will receive a single administration of each treatment in this order during three consecutive clamps
干预措施: ZT-01 low dose (Drug)
Treatment order: low dose, placebo, high dose
Subjects will receive a single administration of each treatment in this order during three consecutive clamps
干预措施: ZT-01 high dose (Drug)
Treatment order: low dose, placebo, high dose
Subjects will receive a single administration of each treatment in this order during three consecutive clamps
干预措施: Placebo (Drug)
Treatment order: low dose, high dose, placebo
Subjects will receive a single administration of each treatment in this order during three consecutive clamps
干预措施: ZT-01 low dose (Drug)
Treatment order: low dose, high dose, placebo
Subjects will receive a single administration of each treatment in this order during three consecutive clamps
干预措施: ZT-01 high dose (Drug)
Treatment order: low dose, high dose, placebo
Subjects will receive a single administration of each treatment in this order during three consecutive clamps
干预措施: Placebo (Drug)
Treatment order: high dose, placebo, low dose
Subjects will receive a single administration of each treatment in this order during three consecutive clamps
干预措施: ZT-01 low dose (Drug)
Treatment order: high dose, placebo, low dose
Subjects will receive a single administration of each treatment in this order during three consecutive clamps
干预措施: ZT-01 high dose (Drug)
Treatment order: high dose, placebo, low dose
Subjects will receive a single administration of each treatment in this order during three consecutive clamps
干预措施: Placebo (Drug)
Treatment order: high dose, low dose, placebo
Subjects will receive a single administration of each treatment in this order during three consecutive clamps
干预措施: ZT-01 low dose (Drug)
Treatment order: high dose, low dose, placebo
Subjects will receive a single administration of each treatment in this order during three consecutive clamps
干预措施: ZT-01 high dose (Drug)
Treatment order: high dose, low dose, placebo
Subjects will receive a single administration of each treatment in this order during three consecutive clamps
干预措施: Placebo (Drug)
结局指标
主要结局
Change in glucagon between euglycemia and hypoglycemia
时间窗: During each clamp, up to 12 weeks
Mean and peak glucagon level during euglycemia and each hypoglycemic period of the clamp
次要结局
- Insulin infused(During each clamp, up to 12 weeks)
- Change in growth hormone between euglycemia and hypoglycemia(During each clamp, up to 12 weeks)
- Insulin infusion rate(During each clamp, up to 12 weeks)
- Change in catecholamines between euglycemia and hypoglycemia(During each clamp, up to 12 weeks)
- Change in cortisol between euglycemia and hypoglycemia(During each clamp, up to 12 weeks)