Conditions: Pre-Diabetes
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 60
Healthy volunteers: no

Brief summary:
This is a single-centre, 16-week, randomized, double-blind, placebo-controlled, 3-treatment arm pilot study to evaluate the efficacy and safety of BTI320 in the treatment of high risk subjects with pre-diabetes.

This is a pilot study aiming to test whether taking a medicine named BTI320 that slows down carbohydrate absorption in the gut, will lower blood sugar. The study aims to recruit 60 individuals in Hong Kong. To take part in the study, subjects must have pre-diabetes, that is, they have blood sugar levels that are above normal but not reaching diabetes range. The medicine BTI320 is currently licensed as a health supplement in Hong Kong and is known alternatively as SUGARDOWN®. The investigators are comparing the effectiveness of BTI320 against a dummy tablet. Both tablets look and taste identical and during the study, subjects will not know which of these tablets they are taking. There is a 4 in 5 chance of receiving active medication and 1 in 5 chance of receiving placebo. Subjects will be followed up closely every 2 to 4 weeks for a period of time up to 22 weeks.

The study visits will take between 30 minutes to 3 hours, depending on additional checks that are required on a particular visit including oral glucose tolerance test and meal tolerance test. At visits involving meal tolerance test, subjects will be required to stay for approximately 3 hours. In addition, at Visit 2, Visit 4 and 3 days before Visit 7, a continuous glucose monitoring system device will be installed.

Throughout the study period, subjects will return to the study center for check-ups including careful enquiry about whether they have developed any side-effects from taking the medication, physical examination, as well as blood tests.

Detailed description:
In a recent national survey, 11% of adults in China have diabetes and 50% have pre-diabetes defined by fasting plasma glucose (FPG) 5.6-6.9 mmol/l and/or 2-hour post glucose (PG) 7.8-11.0 mmol/L using 75 gram oral glucose tolerance test (75g OGTT) and/or glycated haemoglobin (HbA1c) 5.7-6.4%. Depending on the presence of other risk factors, the annual conversion rate of pre-diabetes averages 3-10% with pre-diabetes associated with 1.5-2.0 fold increased risk for cardiovascular disease. Once diabetes is established, life expectancy is reduced by 6 years if not diagnosed, treated or controlled, especially in young-to-middle aged subjects who will face long disease duration of diabetes.

In the Hong Kong Diabetes Registry, depending on control of glucose and other risk factors, 3-10% of Chinese subjects with diabetes may die or develop a major event every year including heart disease, stroke, kidney failure and /or all-site cancer.

Besides glycaemic control as defined by HbA1c, post prandial hyperglycaemia and glycaemic variability have also been shown to predict cardiovascular and renal events in both pre-diabetic and diabetic patient. Genetic variants discovered in large-scale epidemiological studies including those from China and Hong Kong have been found to be associated with beta cell dysfunction which can be further exacerbated by glucotoxicity and lipotoxicity, often due to co-existing obesity giving rise to early onset diabetes. Several studies including those from Asian populations indicated that subjects with pre-diabetes exhibit reduced early phase insulin secretion resulting in postprandial hyperglycaemia which can impose metabolic stress on the beta cells leading to eventual beta cell failure.

BTI320, also known as SUGARDOWN®, is derived from galactomanan which acts by blocking the key carbohydrate hydrolyzing enzymes including amylase, maltose, lactose and sucrose in the gastrointestinal tract. It also acts to bind to ingested polysaccharides and slow their absorption with each meal thereby reducing post prandial glucose excursion. The mechanism of action for BTI320 is similar to Acarbose®, an alpha glucosidase inhibitor, which has been shown to improve glycaemic control and has been approved for prevention of diabetes in China.

24-hour continuous glucose monitoring system (CGMS) measures mean blood glucose (MBG), mean area under the curve for blood glucose above 10mmol/l (180mg/dl) (AUC-180), mean postprandial maximum glucose (MPMG), mean amplitude of glucose excursion (MAGE) over 72 hours. These parameters correlate well with plasma fructosamine (FA) alternatively known as glycated albumin, which reflects short-term glycaemic control during the preceding 2 weeks.

Arms:
arm 1: three times daily, oral for 16 weeks arm 2: three times daily, oral for 16 weeks arm 3: 2 tablets three times daily, oral for 16 weeks

Interventions: intervention 1: BTI320 intervention 2: BTI320 matching placebo
Intervention descriptions: intervention 1: BTI320, also known as SUGARDOWN®, is derived from galactomanan which blocks key enzymes that break down carbohydrate in the gut. BTI320 therefore helps to slow down the absorption of carbohydrates to lower post-meal blood sugar. intervention 2: Placebo

Protocol document: