Dose Comparisons of Leucine-Metformin Combinations on Blood Glucose Levels In Type 2 Diabetic Patients

NCT ID: NCT02151461

Last Updated: 2018-02-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2016-01-31

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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Low Metformin

3 capsules BID with each capsule containing 366.7 mg L-Leucine and 41.7 mg of metformin

Group Type: EXPERIMENTAL

Low Metformin

Intervention Type: DRUG

1100 mg L Leucine in combination with 125 mg of Metformin BID

Mid Metformin

3 capsules BID with each capsule containing 366.7 mg L-Leucine and 83.3 mg of metformin

Group Type: EXPERIMENTAL

Mid Metformin

Intervention Type: DRUG

1100 mg of Leucine in combination with 250 mg Metformin BID

High Metformin

3 capsules BID with each capsule containing 366.7 mg L-Leucine and 166.7 mg of metformin

Group Type: EXPERIMENTAL

High Metformin

Intervention Type: DRUG

1100 mg of Leucine in combination with 500 mg Metformin BID

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.

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

500 mg metformin BID until day 14 with dose escalation at day 14 to 850 mg metformin BID

Interventions

Low Metformin

1100 mg L Leucine in combination with 125 mg of Metformin BID

Intervention Type: DRUG

Metformin

500 mg metformin BID until day 14 with dose escalation at day 14 to 850 mg metformin BID

Intervention Type: DRUG

Mid Metformin

1100 mg of Leucine in combination with 250 mg Metformin BID

Intervention Type: DRUG

High Metformin

1100 mg of Leucine in combination with 500 mg Metformin BID

Intervention Type: DRUG

Other Intervention Names

Metformin; Leucine; L-Leucine; Metformin; Leucine; L-Leucine; Metformin; Leucine; L-Leucine

Eligibility Criteria

Inclusion Criteria

• Over age 18 at study entry.
• Male, or female, if female, meets all of the following criteria:
• Not breastfeeding
• Post-menopausal or negative pregnancy test result (human chorionic gonadotropin, beta subunit [β- hCG]) at Screening (Visit 1) (not required for hysterectomized females)
• If of childbearing potential and sexually active, must practice and be willing to continue to practice appropriate birth control
• Is diagnosed with type 2 diabetes mellitus and either not adequately controlled by: diet and exercise alone or diet and exercise plus a single, first line treatment for type 2 diabetes.
• If treated with an oral anti-diabetes agent, be willing and able to withdraw from therapy for 4 weeks after the screening visit and prior to initiating study mediation at Baseline (Day 1/Visit 4).
• Be willing to avoid acetaminophen use for intervals up to 10 days as required for study procedures (see Section 4.6)
• Has a fasting plasma glucose ≥126 mg/dL to ≤220 mg/dL at Screening
• Has an HbA1c ≥7% to ≤8.5% at Screening
• Has a BMI ≤40 kg/m2
• Clinical laboratory tests (hematology, clinical chemistry, and urinalysis) either normal or abnormal but consistent with type 2 diabetes mellitus.
• Is able to read, understand, and sign the informed consent forms (ICF) and if applicable, an authorization to use and disclose protected health information form (consistent with health insurance portability and accountability act of 1996 [HIPAA] legislation), communicate with the investigator, and understand and comply with protocol requirements.

• Participation in a weight loss program within the past 3 months.
• Weight change by more than 10 pounds during the past month.
• History of alcohol or substance abuse in the past 3 months or a positive screen for alcohol or drugs of abuse at screening.
• Has received any investigational drug within 3 months of Screening.
• Has donated blood within 3 months before Screening or is planning to donate blood during the study.
• Has known allergies or hypersensitivity to metformin or leucine
• Is employed, contracted or has an immediate family member directly affiliated with NuSirt Biopharma.

Exclusion Criteria

• Clinically significant renal dysfunction
• If using any of the following medications, has not been on a stable treatment regimen for a minimum of 4 weeks prior to screening:

Lipid-lowering agents Anti-hypertensive medications Thyroid replacement therapy Non-steroidal anti-inflammatory agents

• Unable to perform self-blood glucose monitoring employing a glucose meter.
• History of active cardio- or cerebro-vascular disease with an event within the previous 6 months
• Gastrointestinal disorders
• Endocrine disorders other than type 2 diabetes
• Chronic infection
• Hepatic disease
• Neurological or psychiatric diseases
• History of other psychiatric disorders

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NuSirt Biopharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Orville G Kolterman, MD

Role: STUDY_CHAIR

NuSirt Biopharma

Locations

Catalina Research Institute

Chino, California, United States

Palm Beach Research

Palm Beach, Florida, United States

Meridien Research

Tampa, Florida, United States

River Birch Research Alliance

Blue Ridge, Georgia, United States

Meridian Research

Savannah, Georgia, United States

Streling Research Group

Cincinnati, Ohio, United States

Medical Research South

Charleston, South Carolina, United States

Meharry Medical College

Nashville, Tennessee, United States

Vanderbilt University Medical Center, Diabetes, Endocrinology, and Metabolism

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

NS-0100-01

Identifier Type: -

Identifier Source: org_study_id