Dose Comparisons of Leucine-Metformin Combinations on Blood Glucose Levels In Type 2 Diabetic Patients
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|ClinicalTrials.gov Identifier: NCT02151461|
Recruitment Status : Completed
First Posted : May 30, 2014
Results First Posted : February 5, 2018
Last Update Posted : February 27, 2018
|Condition or disease||Intervention/treatment||Phase|
|Type 2 Diabetes Mellitus||Drug: Low Metformin Drug: Metformin Drug: Mid Metformin Drug: High Metformin||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||96 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
|Study Start Date :||July 2014|
|Actual Primary Completion Date :||August 2015|
|Actual Study Completion Date :||January 2016|
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
- Change From Baseline to Day 28 in Absolute Plasma Glucose Area Under the Curve (AUC) 0-3hr [ Time Frame: 0, 15min, 30min, 45min, 1hr, 1.5hrs, 2hrs, 2.5hrs and 3 hrs ]The primary endpoint for NS 0100 01 was the absolute plasma glucose AUC (0-3 hr) change from Day 1 to Day 28.
- Change From Baseline to Day 28 in Incremental Plasma Glucose Area Under the Curve (AUC) [ Time Frame: Baseline, Day 28 ]The baseline incremental (baseline-subtracted) glucose AUC0-3h was evaluated for treatment differences at baseline.
- Change in Fasting Plasma Glucose [ Time Frame: Baseline, Day 28 ]Change in fasting plasma glucose for the fixed dose leucine and metformin combination treatments A, B and C was evaluated.
- Change in Hemoglobin A1c (HbA1c) [ Time Frame: Baseline, Day 28 ]Changes in HbA1c which is a marker of long-term glucose control was assessed.
- Change in Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) [ Time Frame: Baseline, Day 28 ]Effect on insulin sensitivity across fixed-dose leucine and metformin combination treatments or the standard metformin reference treatment.
- Change In 7-Point Glucose Profiles [ Time Frame: Baseline, Day 7, Day 21, Day 28 ]The meal induced glucose change in pre-meal and post-meal glucose were measured 7 times during the day. Subjects self-monitored blood glucose (preprandial and postprandial) concentrations at least 7 times, including before and 1 to 2 hours after breakfast, lunch, dinner, and snacks). For each study day, the pre-meal values from the 7 point test for each subject were averaged to generate a single pre-meal glucose value. Similarly, for each study day the post-meal values from the 7-point test for each subject were averaged to generate a single post-meal glucose value. The average change from baseline (i.e., [(Mean Pre/Post-meal value at Day 28 - Mean Pre/Post-meal value at Baseline) + (Mean Pre/Post-meal value at Day 21- Mean Pre/Post-meal value at Baseline) + (Mean Pre/Post-meal value at Day 7- Mean Pre/Post-meal value at Baseline)]/ 3) over multiple time points listed in Time Frame. The mean pre-meal and post-meal values for baseline, day7, day 21 and day28 were used for comparison.
- Plasma Insulin Absolute and Incremental Meal Tolerance Test Area Under the Curve (AUC) 0-2hr [ Time Frame: Baseline,Day 28 ]Change in meal tolerance test insulin area under the curve (0-2 hr) from Day 1 to Day 28 for fixed-dose leucine and metformin combination treatments.
- Change From Baseline to Day 28 in Fasting Plasma Insulin Concentration [ Time Frame: Baseline, Day 28 ]Effect on fasting plasma insulin concentrations across fixed-dose leucine and metformin combination treatments or the standard metformin reference treatment was evaluated.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|