BTI320 (SUGARDOWN®) on Post-Prandial Hyperglycaemia in Subjects With Pre-Diabetes
Condition: Pre-Diabetes
MeSH terms: Diabetes Mellitus; Hyperglycemia; Prediabetic State; Glucose Intolerance
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): BTI320; BTI320 matching placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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.; Placebo
Other intervention name(s): SUGARDOWN®
Intervention MeSH terms: PAZ320
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment