Identification of Biometric Marker(s) Capable of Detecting Early Prediabetes: Clinical Trial 1: Antagonism of Hepatic Muscarinic Receptors Attenuates the Postprandial Actions of Hepatic Insulin Sensitizing Substance (HISS)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- SciMar Ltd.
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Time course change in serum glucose
研究概览
简要总结
The proposed clinical trial is a controlled study of n=24 healthy adult individuals tested in both the Meal-Induced Insulin Sensitization (MIS) state and, following atropine blockade, Absence of Meal-Induced Insulin Sensitization (AMIS) state to differentiate the postprandial glycemia, insulinemia, triglyceride and Hepatic Insulin Sensitizing Substance (HISS) levels in the two states.
The purpose of this study is the identification and development of biometric markers which incorporate the actions and interplay between insulin and HISS. Overall, the study aims to:
- Utilize a standardized test meal to detect one of the earliest pathologies present during the development of insulin resistance, pre-diabetes and obesity.
- Compare the control (HISS positive) and post-atropine (HISS negative) tests with the acute consequences of absence of MIS (AMIS) being graphically shown over 4 hours of postprandial nutrient partitioning, tracking the full metabolomic dynamic pattern.
- To establish values for potential indices (bio-impedance, hand-grip strength, spirometry) in young, fit, lean individuals. These values will be used as baselines for comparative analysis in future clinical trials employing individuals with various degrees of insulin resistance to full Type 2 Diabetes.
- Demonstrate that these biometric markers can differentiate between the HISS positive and HISS negative post-meal state with the future aim of using the biomarkers for the detection of early prediabetes.
The study will involve 4 study visits: Visit 1 - Prescreening; Visit 2 - Screening; Visit 3 - Liquid test meal administration and postprandial blood collection; Visit 4 - Atropine administration + Liquid test meal administration and postprandial blood collection.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy (absence of disease)
- •Not on any prescribed medications
- •Male and female (in follicular phase)
- •20-40 years of age
- •Normal BMI range (18.5-24.9)
- •Able to understand and communicate in English
- •Comfortable having blood drawn
- •Willing to provide urine and blood samples
- •Normal urinalysis, Complete Blood Count (CBC) and blood chemistry laboratory test results
- •Willingness to undergo bioimpedance testing, handgrip dynamometry (strength) testing, and pulmonary function test (spirometry).
- •Willingness to undergo atropine administration
- •Willingness to fast for 12 hours prior to the screening and testing days
- •Willingness to undergo Electrocardiogram (ECG) and Heart Rate Variability (HRV) testing
- •Willingness to use non-hormonal birth control methods throughout the study duration
排除标准
- •Glaucoma, Pyloric Stenosis
- •Obstructive Uropathy, Urinary Incontinence
- •Diabetes, Cardiovascular Disease, including Heart Murmurs
- •Diagnosed or with history (last 6 months) and receiving pharma or professional therapy for Psychological/Psychiatric issues
- •Inflammatory conditions, including IBD
- •Subject on any hormone treatment, including thyroid hormone
- •Subject on any steroid therapy including cortisol, or any anti-inflammatory agent
- •Sensitivity to anti-cholinergic drugs
- •Allergic or have sensitivities to rubbing alcohol during blood draw
- •Allergy/sensitivity to any component of the standardized test meal (dextrose, lecithin, soy protein)
- •Pregnant women, women of child-bearing potential not willing to use barrier method contraceptives, women trying to get pregnant, and breastfeeding women, women using hormonal birth control
- •Whole blood donation (50-499 ml of whole blood) within 30 days, and more than 499 ml of whole blood 56 days prior to test visit
- •Participants should not donate whole blood for the duration of the trial, and for 30 days following the end of the trial
- •Blood pressure greater than 140/90 mmHg and heart rate greater than or equal to 80 beats per minute
研究组 & 干预措施
Standardized liquid test meal
干预措施: Standardized liquid test meal (Other)
Atropine + Standardized liquid Test meal
干预措施: Atropine + Standardized liquid test meal (Drug)
结局指标
主要结局
Time course change in serum glucose
时间窗: Control: Baseline, and every 30 minutes up to 4 hours after test meal administration; Test: Baseline, 15 mins post atropine and every 30 minutes up to 4 hours after test meal administration
Time course and curve analysis of serum glucose response after the test meal administration with and without atropine pre-treatment.
Time course change in serum insulin
时间窗: Time Frame: Control: Baseline, and every 30 minutes up to 4 hours after test meal administration; Test: Baseline, 15 mins post atropine and every 30 minutes up to 4 hours after test meal administration
Time course and curve analysis of serum insulin response after the test meal administration with and without atropine pre-treatment
Time course change in serum triglycerides
时间窗: Control: Baseline, and every 30 minutes up to 4 hours after test meal administration; Test: Baseline, 15 mins post atropine and every 30 minutes up to 4 hours after test meal administration
Time course and curve analysis of serum triglycerides response after the test meal administration with and without atropine pre-treatment
Time course change in plasma HISS levels
时间窗: Time Frame: Control: Baseline, and every 30 minutes up to 4 hours after test meal administration; Test: Baseline, 15 mins post atropine and every 30 minutes up to 4 hours after test meal administration
Time course and curve analysis of plasma HISS response after the test meal administration with and without atropine pre-treatment
次要结局
- Time course change in serum free fatty acids(Control: Baseline, and every 30 minutes up to 4 hours after test meal administration; Test: Baseline, 15 mins post atropine and every 30 minutes up to 4 hours after test meal administration)
- Time course change in plasma lactate(Control: Baseline, and every 30 minutes up to 4 hours after test meal administration; Test: Baseline, 15 mins post atropine and every 30 minutes up to 4 hours after test meal administration)
- Time frame fasted HOMA-IR (Molar Units)(Control: Baseline fasted Test: 15 mins post atropine)
- Time course change in Meal Induced Glycemia (MIG) scores (Molar Units)(Control: Every 30 minutes up to 4 hours after test meal administration; Test: Every 30 minutes up to 4 hours after test meal administration)