ICH GCP | Clinical Trials Registry

Glycemic Index Laboratories, Inc

Blood sugar levels are controlled by insulin, a hormone made by cells in the pancreas. After a normal meal, carbohydrates are broken down into glucose (blood sugar) which is absorbed from the intestine into the blood leading to a rise in blood glucose which triggers the secretion of insulin. Insulin binds to cells in the liver, muscle and fat, triggering them to take up glucose and bring the blood glucose level back to normal. A high blood sugar level is known as diabetes. The most common form of diabetes, type 2 diabetes, is caused by insulin resistance; that is, a reduced ability of insulin to stimulate glucose uptake into cells. The body compensates for insulin resistance by making more insulin; type 2 diabetes occurs when the pancreas can no longer make enough insulin to control blood glucose. The high blood glucose and insulin levels lead to long-term complications such as heart attacks, kidney failure, reduced sensation and poor circulation in the feet and legs. Reducing blood glucose levels with oral medications and insulin reduces risk of diabetes complications. There are several types of oral medications available for treating diabetes; however, they do not always control blood glucose adequately. In addition, these drugs have complications and are not used to treat insulin resistance and pre-diabetes; a condition when blood glucose is higher than normal but not high enough to be called diabetes. Pre-diabetes often progresses to diabetes over a period months or years. Effective and safe treatments for pre-diabetes could prevent or delay the onset of diabetes. Axulin is a natural health product consisting of a mixture of extracts from herbs and vegetables present in normal diets which has been shown in cell-culture (cells grown in the laboratory) and in animal studies to increase the ability of insulin to stimulate glucose uptake into cells. Thus, Axulin may reduce the blood glucose and insulin levels of subjects without diabetes after eating. Also Axulin may reduce glucose and insulin responses more in insulin-resistant compared to insulin-sensitive subjects. Subjects will take 0g, 2g or 4g or Axulin capsules or Axulin tablets in the morning after an overnight fast; 40min later they will then consume 75g glucose dissolved in 300ml water. Blood glucose, insulin and fats will be measured before and for 2 hours after the glucose drink.

After consumption of a meal, pancreatic secretions of various digestive enzymes results in the breakdown of carbohydrates into monosaccharides including glucose.1 These sugars are subsequently absorbed through the intestinal lumen, resulting in an increased plasma glucose concentration. In response to high glucose levels, pancreatic beta-cells are stimulated to release the hormone insulin which circulates through the bloodstream and binds to insulin-responsive cells including adipocytes (fat tissue), myocytes (muscle tissue), and hepatocytes (liver). The resulting insulin-mediated signaling cascade initiates intracellular glucose uptake within peripheral tissues leading to a corresponding decrease in circulating plasma glucose. In insulin responsive cells glucose uptake stimulation begins after the binding of insulin to Insulin Receptors (IR), which are found on the membrane surface of cells in insulin responsive tissues such as fat, muscle and liver. The IR consists of an extracellular domain which binds to insulin, and an intracellular domain that has a protein tyrosine kinase activity. The binding of Insulin to the IR initiates a series of auto-phosphorylation events within the protein kinase domain that permit interaction and phosphorylation of downstream signaling proteins in the cell that mediate the cellular response to insulin. The resulting signaling complex includes proteins in the Insulin Receptor Substrate (IRS) family known as IRS-1 and IRS-2. These key targets of the insulin signaling pathway link IR activation to downstream signaling cascades that mediate intracellular processes including GLUT4 mediated glucose uptake. Pre-diabetes and Type II diabetes involve an impaired post-receptor response to insulin that hinders the glucose uptake response after meal consumption. Chronic hyperglycemia and the resulting compensatory hyperinsulinemia promote a cohort of acute and chronic sequelae including cardiovascular disease, liver complications, central nervous system degeneration and hyperglycemic osmotic stress. Axulin is a natural health product consisting of a mixture of extracts from herbs and vegetables present in normal diets which was identified by screening more than 100,000 compounds and extracts in a patented cell-culture based assay system targeting the IRS proteins. In vitro, Axulin has marked effects on the IRS-2 branch of the insulin signaling cascade to enhance downstream insulin signaling. Axulin has been shown in animal models to increase glucose uptake in peripheral tissues and decrease circulating blood glucose and triglyceride concentrations. Regular supplementation of the diet with Axulin would be expected to reduce the incidence of associated pre-diabetic and diabetic complications, resulting in an increased quality of life for patients without resorting to current anti-diabetic prescription drugs such as metformin and others that may have substantial unwanted side effects in patients. HYPOTHESES Axulin will reduce postprandial glucose and insulin responses in a dose-dependent fashion in healthy subjects without diabetes. The reduction in glucose and insulin will be relatively greater in insulin-resistant than insulin-sensitive subjects. Subjects will take 0g, 2g or 4g or Axulin capsules or Axulin tablets in the morning after an overnight fast; 40min later they will then consume 75g glucose dissolved in 300ml water. Blood glucose, insulin and triglycerides will be measured fasting and at intervals for 2 hours after the glucose drink.

Completed

2017-04-26

2017-06-21

2017-06-21

Phase 1

Interventional

22

Insulin Resistance, Diabetes 

2017-07-01

N/A

N/A

No

Insulin Resistance , Overweight 

2

N/A

N/A

April 26, 2017

April 28, 2017

May 1, 2017

July 15, 2017

July 15, 2017

July 19, 2017