Clinical trial NCT04625088: Identification of Biometric Marker(s) Capable of Detecting Early Prediabetes: Clinical Trial 1
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: Glucose; Insulin; Prediabetes
Lead sponsor: SciMar Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Source Nutraceutical, Inc.
First posted: 2020-11-12
Enrollment: 24
Sex: ALL
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

Brief summary: 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:

1. Utilize a standardized test meal to detect one of the earliest pathologies present during the development of insulin resistance, pre-diabetes and obesity.
2. 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.
3. 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.
4. 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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 1. 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

Primary outcomes:
measure: Time course change in serum glucose
timeFrame: 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
measure: Time course change in serum insulin
timeFrame: 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
measure: Time course change in serum triglycerides
timeFrame: 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
measure: Time course change in plasma HISS levels
timeFrame: 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
Secondary outcomes:
measure: Time course change in serum free fatty acids
timeFrame: 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
measure: Time course change in plasma lactate
timeFrame: 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
measure: Time frame fasted HOMA-IR (Molar Units)
timeFrame: Control: Baseline fasted Test: 15 mins post atropine
measure: Time course change in Meal Induced Glycemia (MIG) scores (Molar Units)
timeFrame: Control: Every 30 minutes up to 4 hours after test meal administration; Test: Every 30 minutes up to 4 hours after test meal administration
Other outcomes:
Locations:
city: Winnipeg
country: Canada
facility: Kalo Medical Clinic
state: Manitoba
Study officials:
affiliation: Source Nutraceutical, Inc.
name: Vanu Ramprasath, PhD
role: PRINCIPAL_INVESTIGATOR
References: