Dose Comparisons of Leucine-Metformin Combinations on Blood Glucose Levels In Type 2 Diabetic Patients
Type 2 Diabetes Mellitus
Drug: Low Metformin
Drug: Mid Metformin
Drug: High Metformin
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Randomized, Double-Blind, Active-Controlled Study to Evaluate the Effect of Various Fixed-Dose Leucine and Metformin Combinations (NS-0100) Versus Standard Metformin Monotherapy on Glycemic Control in Subjects With Type 2 Diabetes|
- Change In Fasting Plasma Glucose [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]Fasting plasma glucose levels will be measured in a variety of ways including; Standard fasting plasma glucose lab readings, seven point glucose profiles, and through continuous glucose monitoring.
- Gastrointestinal Effects [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]Effects on gastrointestinal symptoms patients experienced by questions answered.
- Change in Baseline-Corrected Plasma Glucose and Insulin Area Under The Concentration Curves [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]Plasma blood glucose levels will be accessed through continuous glucose monitoring and through standard 3 hour meal tolerance tests.
- Change in Insulin Secretory Rates [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]Insulin secretory rates will be tested using standard 3 hour meal tolerance testing.
- Change in Fasting Plasma Lipids [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]Fasting plasmid lipids will be tested by standard lipid chemistry
- Change in HbA1c [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]HbA1c will be examined through standard chemistry
- Change in HOMA-IR [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]HOMA-IR will be evaluated through standard chemistry
- Change In 7-Point Glucose Profiles [ Time Frame: Baseline, Day 7, Day 21, Day 28 ] [ Designated as safety issue: No ]7 point glucose profiles will be examined by obtaining plasma glucose levels at 7 different time points
- Change In Serial Blood Glucose Concentrations [ Time Frame: Baseline,Day 28 ] [ Designated as safety issue: No ]Assessed by continuous glucose monitoring
- Safety and Tolerability [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]Patients will be monitored and asked about any adverse events or problems they encounter as a result of the study drug
|Study Start Date:||July 2014|
|Estimated Study Completion Date:||September 2015|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
Experimental: Low Metformin
3 capsules BID with each capsule containing 366.7 mg L-Leucine and 41.7 mg of metformin
Drug: Low Metformin
1100 mg L Leucine in combination with 125 mg of Metformin BID
Experimental: Mid Metformin
3 capsules BID with each capsule containing 366.7 mg L-Leucine and 83.3 mg of metformin
Drug: Mid Metformin
1100 mg of Leucine in combination with 250 mg Metformin BID
Experimental: High Metformin
3 capsules BID with each capsule containing 366.7 mg L-Leucine and 166.7 mg of metformin
Drug: High Metformin
1100 mg of Leucine in combination with 500 mg Metformin BID
Experimental: Metformin Monotherapy
3 Capsules BID each containing 166.7 mg of metformin with dose escalation to 283.3 mg capsules BID (1,700 mg/Day) at Day 14.
500 mg metformin BID until day 14 with dose escalation at day 14 to 850 mg metformin BID
This is a randomized, 4-week, active-controlled, double-blind study to evaluate the effect of various fixed-dose combinations of leucine and metformin compared to standard metformin monotherapy on glycemic control. In this study, standard metformin therapy will be defined as 1000 g/day for Day 1 to Day 14 and then escalated to 1700 g/day for Day 15 to Day 28. Subjects meeting all inclusion criteria and no exclusion criteria will be randomized to one of four treatment arms.
The primary objective of the study is to evaluate the change in fasting plasma glucose from Baseline (Day 1) to Week 4 (Day 28) in subjects receiving various fixed-dose combinations of leucine and metformin compared to standard metformin monotherapy. Secondary objectives will also assess changes in baseline-corrected plasma glucose and insulin area under the concentration curves from baseline to day 28 and changes in insulin secretory rates as assessed during a 3-hour meal tolerance test. Finally the effects of gastrointestinal symptoms will be assessed by subject questionnaires.
The study will include a total of 3 periods: screening or washout of current diabetic monotherapy, a pre-treatment period to ensure subjects will be compliant, and a treatment period of 4 weeks, with the first dosing of medication on day 1 of the study. Each day blood glucose readings will be measured and recorded by patients. Three-hour standardized meal tests will be performed at Baseline (Day 1) and at Study Termination (Day 28). In addition, two, 7-day continuous glucose assessments will be conducted, as well as two seven point glucose profiles. Patients will also be asked about any gastrointestinal side effects they experience.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02151461
|United States, California|
|Catalina Research Institute|
|Chino, California, United States, 91710|
|United States, Florida|
|Palm Beach Research|
|Palm Beach, Florida, United States, 33409|
|Tampa, Florida, United States, 33606|
|United States, Georgia|
|River Birch Research Alliance|
|Blue Ridge, Georgia, United States, 30513|
|Savannah, Georgia, United States, 31406|
|United States, Ohio|
|Streling Research Group|
|Cincinnati, Ohio, United States, 45219|
|United States, South Carolina|
|Medical Research South|
|Charleston, South Carolina, United States, 29407|
|United States, Tennessee|
|Meharry Medical College|
|Nashville, Tennessee, United States, 37208|
|Vanderbilt University Medical Center, Diabetes, Endocrinology, and Metabolism|
|Nashville, Tennessee, United States, 37232|
|Study Chair:||Orville G Kolterman, MD||NuSirt Biopharma|