Evaluate Effects of Sprinkled Format REDUCOSE in a Carbohydrate-rich, Mixed Meal on Post-prandial Glycemia

Study Overview
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Brief Summary
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This is a mechanistic, single-center, double-blind, placebo- and active-controlled, three-time-period, crossover study to evaluate the effect of sprinkled format REDUCOSE compared to placebo (double-blind; confirmative) and active control (open-label; acarbose - explorative) on post prandial glycemia in Asian patients with type 2 diabetes.

Official Title
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A Randomized, Double-blind, Placebo- and Active-Controlled, Single-Center, Three-time-period, Crossover Study to Evaluate the Effects of Sprinkled Format REDUCOSE on Post-Prandial Glycemic Response in Asian Patients With Type 2 Diabetes

Conditions
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Dietary Supplement

Intervention / Treatment
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* Dietary Supplement: Dietary Supplement: Sprinkled Format REDUCOSE.
* Other: Reference control
* Other: Active comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to sign written informed consent prior to study entry. Participants who self-identify as Asian; male or female, >18 years of age. Established diagnosis of type 2 diabetes (documented by either HbA1c 6.5 - 10.0% or a documented diagnosis of type 2 diabetes). Treatment naïve or on active therapy with metformin at a daily dose of 500-3000 mg at screening. Dose of metformin must have been stable for at least 3 months prior to screening. Participants must have a hematocrit value greater than or equal to 34.0% for females and 40% for males. Participants must have a hemoglobin value greater than or equal to 11.0 g/dL for females and 13.5 g/dL for males. Exclusion Criteria: Fasting plasma glucose >220 mg/dl at screening. Impaired kidney function, eGFR of <60 mL/min/1.73 m2 at screening. BMI >35 kg/m2. Weight ≤ 50 kg. Elevated liver transaminase > 3 ULN at screening. Ongoing or recent (i.e. < 3 month) treatment with any oral or injectable glucose-lowering drug other than metformin. Ongoing or recent (i.e. < 3 month) injectable insulin therapy. Ongoing or recent (i.e. < 3 month) weight loss interventions (e.g. dietary weight loss programs) or any history of bariatric surgery or any documented weight loss >5% within previous 6 months. Ongoing or recent (i.e. < 3 month) treatment with anorectic drugs, systemic steroids, medications known to affect gastric motility, or any condition known to affect gastro-intestinal integrity and food absorption. Major medical/surgical event requiring hospitalization in the last 3 months. Known allergy and intolerance to product components or paracetamol. Alcohol intake higher than 2 servings per day. A serving is 0.4 dl of strong alcohols, 1 dl of red or white wine, or 3 dl of beer. Are unable to comply with protocol procedures in the opinion of the investigator. Have a hierarchical link with the research team members. Positive pregnancy test or breast-feeding at screening. Participants who have been dosed in another clinical study with any investigational drug/new chemical entity within 30 days or 5 half-lives (whichever is longer) prior to screening. Donation of blood or significant amount of blood loss within 8 weeks prior to screening. Participants must also agree to not donate blood within 8 weeks after their last visit.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ARM A: Sprinkled Format REDUCOSE<br>2 G powder sprinkle containing 250 mg REDUCOSE (mulberry leaf extract - 250 mg - 5% DNJ) + fiber, vitamin D, and chromium picolinate | Dietary Supplement: Dietary Supplement: Sprinkled Format REDUCOSE.<br>* 2 G powder sprinkle containing 250 mg REDUCOSE (mulberry leaf extract - 250 mg - 5% DNJ) + fiber, vitamin D, and chromium picolinate<br>|
| Placebo Comparator: ARM B: Placebo B: Standard Meal<br>A placebo matching to the test product will be used as control | Other: Reference control<br>* A placebo matching to the test product will be used as control<br>|
| Placebo Comparator: ARM C: Placebo C: Acarbose<br>Acarbose 100 mg tablet (provided in open-label format) | Other: Active comparator<br>* Acarbose 100 mg tablet (provided in open-label format)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-prandial glycemic excursion (ARMs A and B) | Incremental area under the curve post-prandial glycemic excursion (iAUC 0-1h, iAUC 0-2h, iAUC 0-3h). | 0 ,15, 30, 60, 120, and 180 minutes. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2h post-prandial glucose levels (ARMs A and B) | Incremental area under the curve 2h post-prandial glucose levels | 0 ,15, 30, 60, and 120 minutes. | 
| Total glucose (All ARMS) | Total glucose AUC 0-1h (tAUC 0-1h, tAUC 0-2h, tAUC 0-3h) | 0 ,15, 30, 60, 120, and 180 minutes. | 
| Plasma glucose iCmax (ARMs A and B) | Plasma glucose iCmax | 0 ,15, 30, 60, 120, and 180 minutes. | 
| Plasma glucose Tmax (ARMs A and B) | Plasma glucose Tmax | 0 ,15, 30, 60, 120, and 180 minutes. | 
| Plasma glucose AUC (ARMs A and B) | protocol states (iAUC 0-3h, tAUC 0-3h) | 0 ,15, 30, 60, 120, and 180 minutes. | 
| Serum insulin (All ARMs) | Serum insulin (iAUC 0-3h, iCmax, Tmax, tAUC 0-3h) | 0 ,15, 30, 60, 120, and 180 minutes. | 
| Plasma GLP-1 (ARMs A and B) | Plasma GLP-1 (iAUC 0-2h, iCmax, Tmax, tAUC 0-2h) | 0 ,15, 30, 60, 120, and 180 minutes. | 
| Plasma GIP (ARMs A and B) | Plasma GIP (iAUC 0-2h, iCmax, Tmax, tAUC 0-2h) | 0 ,15, 30, 60, 120, and 180 minutes. | 
| Plasma interleukin-6 (ARMs A and B) | Plasma interleukin-6 (IL-6) (iAUC 0-2h, iCmax, Tmax, tAUC 0-2h) | 0 ,15, 30, 60, 120, and 180 minutes. | 
| Gastric emptying (ARMs A and B) | Gastric emptying (iAUC 0-1h, tAUC 0-1h, iAUC 0-3h, tAUC 0-3h, Cmax and Tmax for paracetamol) | 0 ,15, 30, 60, 120, and 180 minutes. | 
| Matsuda Index (ARMs A and B) | Matsuda Index | 0, 30, 60, and 120 minutes. |