Acute Effect of Axulin on Blood Glucose and Serum Insulin Responses in Healthy Lean and Overweight Humans
Acute Effect of Axulin on Blood Glucose and Serum Insulin Responses in Healthy Lean and Overweight Humans
Sponsors
Source
Glycemic Index Laboratories, Inc
Oversight Info
Has Dmc
No
Is Fda Regulated Drug
No
Is Fda Regulated Device
No
Brief Summary
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.
Detailed Description
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.
Overall Status
Completed
Start Date
2017-04-26
Completion Date
2017-06-21
Primary Completion Date
2017-06-21
Phase
Phase 1
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
Percentage reduction in AUC for glucose after Axulin capsules in n=22 subjects. |
2 hours |
Secondary Outcome
Measure |
Time Frame |
Blood glucose AUC |
2 hours |
Serum insulin AUC |
2 hours |
Percentage reduction in insulin AUC |
2 hours |
Insulinogenic index |
baseline and 30min |
Matsuda insulin sensitivity index |
2 hours |
ISSI-2 index of beta-cell function |
2 hours |
Enrollment
22
Condition
Intervention
Intervention Type
Other
Intervention Name
Description
16 x 250mg placebo capsules with 250ml water
Arm Group Label
Lean
Overweight/Obese
Intervention Type
Other
Intervention Name
Description
8 x Axulin capsules plus 8 x 250mg placebo capsules with 250ml water
Arm Group Label
Lean
Overweight/Obese
Intervention Type
Other
Intervention Name
Description
16 x Axulin capsules with 250ml water
Arm Group Label
Lean
Overweight/Obese
Intervention Type
Other
Intervention Name
Description
250ml water
Arm Group Label
Lean
Overweight/Obese
Intervention Type
Other
Intervention Name
Description
2 x 1g Axulin tablets with 250ml water
Arm Group Label
Lean
Overweight/Obese
Intervention Type
Other
Intervention Name
Description
4 x 1g Axulin tablets with 250ml water
Arm Group Label
Lean
Overweight/Obese
Eligibility
Criteria
Inclusion Criteria:
- Subjects 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)
Gender
All
Minimum Age
18 Years
Maximum Age
60 Years
Healthy Volunteers
Accepts Healthy Volunteers
Overall Official
Last Name |
Role |
Affiliation |
Thomas MS Wolever, MD, PhD |
Principal Investigator |
Glycemic Index Laboratories, Inc |
Location
Facility |
Glycemic Index Laboratories, Inc. Toronto Ontario M5C 2N8 Canada |
Location Countries
Country
Canada
Verification Date
2017-07-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Has Expanded Access
No
Condition Browse
Number Of Arms
2
Intervention Browse
Mesh Term
Insulin
Arm Group
Arm Group Label
Lean
Arm Group Type
Other
Description
Subjects with BMI >18.5 and <25.0kg/m²
Arm Group Label
Overweight/Obese
Arm Group Type
Other
Description
Subjects with BMI ≥25.0 and <35.0kg/m²
Firstreceived Results Date
N/A
Other Outcome
Measure
Effect of axulin in lean vs overweight subjects
Time Frame
2 hours
Description
Percentage reduction in glucose AUC in lean subjects compared to overweight subjects
Measure
Effect of axulin capsules vs axulin tablets
Time Frame
2 hours
Description
Percentage reduction in glucose AUC elicited by axulin capsules compared to the same dose of axulin tablets
Patient Data
Sharing Ipd
No
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Crossover Assignment
Intervention Model Description
Each subject in 2 subject groups will undergo each of 6 treatments
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Capsule treatments will be fully blinded. Tablet treatments will be open label.
Study First Submitted
April 26, 2017
Study First Submitted Qc
April 28, 2017
Study First Posted
May 1, 2017
Last Update Submitted
July 15, 2017
Last Update Submitted Qc
July 15, 2017
Last Update Posted
July 19, 2017
Pending Results
Submitted
October 11, 2019
November 25, 2019
Returned
November 1, 2019
ClinicalTrials.gov processed this data on December 06, 2019
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Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.