Acute Effect of HP-211 (Axulin) on Blood Glucose and Serum Insulin Responses in Healthy Lean and Overweight Humans
Condition: Insulin Resistance, Diabetes
MeSH terms: Overweight; Insulin Resistance
Intervention: Placebo capsules; 2g capsules; 4g capsules; Water Control; 2g tablets; 4g tablets
Intervention description: 250ml water with 16 x 250mg placebo capsules; 250ml water with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules; 250ml water with 16 x 250mg capsules containing Axulin powder; 250ml water; 250ml water with 2 x 1g tablets containing Axulin powder; 250ml water with 4 x 1g tablets containing Axulin powder
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Each participant in 2 participant groups will undergo each of 6 treatments
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Capsule treatments will be fully blinded. Tablet treatments will be open label.
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Blood sugar levels are controlled by insulin, a hormone made by cells in the pancreas. After
      a meal, carbohydrates are broken down into glucose (blood sugar) which is absorbed from the
      intestine into the blood leading to a rise in 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 diabetic 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 prediabetes -
      a condition when blood glucose is higher than normal but not high enough to be classified as
      diabetes. Prediabetes often progresses to diabetes over a period of months or years.
      Effective and safe treatments for prediabetes could prevent or delay the onset of diabetes.

      Axulin is a natural health product consisting of a mixture of extracts - derived from herbs
      and vegetables present in normal diets - which has been shown in cell culture and in animal
      studies to increase the ability of insulin to stimulate glucose uptake into cells. The active
      ingredient in Axulin is a botanical extract designated HP-211. Thus, HP-211 may reduce the
      blood glucose and insulin levels of subjects without diabetes after eating. HP-211 may also
      reduce glucose and insulin responses to a larger extent in insulin-resistant as compared to
      insulin-sensitive subjects.

      Subjects will take 0g, 2g, or 4g of capsules or tablets in the morning after an overnight
      fast; 40 minutes later they will consume 75g glucose dissolved in 300ml water. Blood glucose,
      insulin and fats will be measured before and for 2 hours after the glucose drink.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants taking stable doses (for at least 4 weeks of signing the consent form) of
             the birth control pill, thyroxin replacement therapy, statins, fibrates, cholesterol
             absorption inhibitors, anti-hypertensive medications, asprin, non-steroidal
             anti-inflammatories and/or mild anxiolytics or sedatives can be included.

        Exclusion Criteria:

          -  Fasting serum glucose >6.9mmol/L (124mg/dL)

          -  HbA1c >6.4%

          -  Fasting serum triglycerides >4.5 mmol/L (399 mg/dL)

          -  Fasting LDL cholesterol >4.99 mmol/L (192 mg/dL)

          -  Blood pressure >149 systolic or >89 diastolic

          -  Serum creatinine, or aspartate- or alanine transaminases >1.2 times upper limit of
             normal

          -  White cell count, red blood cell count, hemoglobin or hematocrit outside normal range

          -  Hospitalization for surgery or a medical condition within 3 months of signing the
             consent form

          -  Use of any drug to treat diabetes

          -  Use of medications other than those listed above or the presence of any condition
             which might, in the opinion of Dr. Wolever, either: 1) make participation dangerous to
             the subject or to others, or 2) affect the results

          -  Allergy or sensitivity to tarragon, chromium, escarole, lettuce, microcrystalline
             cellulose, inulin, food colouring (FD&C Yellow#5 and Blue#1) or vegetable-based
             capsules (silicon dioxide, titanium dioxide, hydroxypropylmethylcellulose)