BACKGROUND: Diabetes is an increasingly common disease that affects 6% of the population. It is a chronic metabolic disorder because the body cannot produce enough insulin or cannot respond well to insulin to control the amount of sugar in the blood. Insulin is a hormone secreted by the pancreas that increases the ability of tissues to absorb blood glucose. After a meal, our body will break down the nutrients in the food we eat, such as carbohydrates. These smaller nutrients are then absorbed in our small intestine into our blood. Without proper insulin function, our body is unable to lower the blood sugar and use the blood sugar correctly, leading to high blood sugar (also known as hyperglycemia). Over time, this can lead to complications in the eyes, nervous system, kidney and heart.
One type of diabetes medications, alpha-glucosidase inhibitors (AGIs), prevent blood sugar spikes (period of out of control high blood sugar levels) in diabetic patients after a meal. This type of medication prevents breakdown of carbohydrates into small sugars that can be absorbed in the gut. AGIs usually work well in preventing blood sugar spikes, but they have a number of side effects such as increased gas, bloating and diarrhea. Because of this, patients usually do not follow the recommended schedule for taking AGIs, which means the medications wont work as well.
The Study Treatment ("Montbretin A") provides another way to control blood sugar spikes after a meal. This method targets an enzyme (substance produced by body to help break down substances) found in the small intestine called human pancreatic amylase (HPA), which helps in the first step of breaking down carbohydrates. The Study Treatment works by blocking HPA from performing its function. This could potentially be used to treat T2D by preventing the initial breakdown of carbohydrates, which can lead to less sugars absorbed to the blood and better blood sugar control. MbA will lead to larger pieces of carbohydrates passed to the colon, reducing the speed of gas produced. This might lead to reduced stomach upsets.
MAIN AIM: To test the safety and tolerability (in terms of stomach-related side effects) of MbA in humans.
METHOD: This is an open-label, first-in-human, single-arm, single-center Phase I clinical trial. Participants will receive increasing dose of MbA (starting from 10 mg to 300 mg) with a standardized meal during the two-week treatment period (Weeks 1 and 2), with follow-up visits scheduled in Week 3 (one week after treatment completion) and Week 12 (nine weeks after treatment completion).
Participants are expected to participate for up to 13 weeks. This include one screening visit (one week prior to start of treatment), 2 weeks of treatment (3 visits per week for a total of 6 visits), and 2 follow-up visits (one week and nine weeks after completing treatment).
The tests that will be done in this study include:
* One blood draw at each visit
* Electrocardiogram (ECG), at screening and the first follow up visit
* Blood sugar checks, including one finger prick and continuous glucose monitoring using a device at screening and each treatment visit
* Questionnaire regarding gastrointestinal symptoms
* Gastro-Intestinal Diary (GID), which needs to be filled in daily after screening and up to one week after treatment period.
