Clinical trial NCT02151461
Conditions: Type 2 Diabetes Mellitus
Keywords: Diabetes Type 2 Diabetes
Sponsor: NuSirt Biopharma
Start date: 2014-07-01; Completion date: 2016-01-01
Enrollment: 96 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The goal of this study is to demonstrate that leucine in combination with a low does of metformin can serve as an adjunct to diet and exercise to improve blood glucose levels in type 2 diabetic subjects. This study will compare three doses of a leucine-metformin combination to the standard metformin dose in controlling blood glucose levels in type 2 diabetic patients.

Detailed description:
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.

Arms: arm 1: 3 capsules BID with each capsule containing 366.7 mg L-Leucine and 41.7 mg of metformin arm 2: 3 capsules BID with each capsule containing 366.7 mg L-Leucine and 83.3 mg of metformin arm 3: 3 capsules BID with each capsule containing 366.7 mg L-Leucine and 166.7 mg of metformin arm 4: 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.
Interventions: intervention 1: Low Metformin intervention 2: Metformin intervention 3: Mid Metformin intervention 4: High Metformin
Intervention descriptions: intervention 1: 1100 mg L Leucine in combination with 125 mg of Metformin BID intervention 2: 500 mg metformin BID until day 14 with dose escalation at day 14 to 850 mg metformin BID intervention 3: 1100 mg of Leucine in combination with 250 mg Metformin BID intervention 4: 1100 mg of Leucine in combination with 500 mg Metformin BID

Protocol documents: