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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by NuSirt Biopharma
Sponsor:
Information provided by (Responsible Party):
NuSirt Biopharma
ClinicalTrials.gov Identifier:
NCT02151461
First received: May 28, 2014
Last updated: August 19, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Low Metformin
Drug: Metformin
Drug: Mid Metformin
Drug: High Metformin
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by NuSirt Biopharma:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 102
Study Start Date: July 2014
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Names:
  • Metformin
  • Leucine
  • L-Leucine
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
Other Names:
  • Metformin
  • Leucine
  • L-Leucine
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
Other Names:
  • Metformin
  • Leucine
  • L-Leucine
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.
Drug: Metformin
500 mg metformin BID until day 14 with dose escalation at day 14 to 850 mg metformin BID
Other Name: Metformin

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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
  • Has been treated (within the last month), is currently treated, or is expected to require or undergo treatment with; any anti-diabetes medications (other than as allowed by the inclusion criteria), oral or parenteral steroids.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02151461

Contacts
Contact: Mary Kosinski, PhD 615-843-9107 mkosinski@nusirt.com

Locations
United States, California
Catalina Research Institute Recruiting
Chino, California, United States, 91710
Contact: Luis Valenzuela, CRC    909-590-4713    LValenzuela@Catalinari.Com   
Contact: Cynthis Pereira, CRC    909-590-4707    CPereira@Catalinari.Com   
Principal Investigator: Mia Moon, MD         
Sub-Investigator: Jeffrey Unger, MD         
United States, Florida
Palm Beach Research Recruiting
Palm Beach, Florida, United States, 33409
Contact: Annette Pitts    561-689-0606    Annette@PalmBeachResearch.com   
Principal Investigator: Mira Baron, MD         
Meridien Research Recruiting
Tampa, Florida, United States, 33606
Contact: Kristen Dewes    813-877-8839    kdewes@meridienresearch.net   
Contact: Jennifer McCaffrey       jmccaffrey@meridienresearch.net   
Principal Investigator: Cynthia Huffman, MD         
United States, Georgia
Meridian Research Recruiting
Savannah, Georgia, United States, 31406
Contact: Kari Pace    912-596-2042    kpace@mcrmed.com   
Contact: Lauren Falcone    (921)-596-2024    LFalcone@mcrmed.com   
Principal Investigator: Paul Bradley, MD         
United States, Ohio
Streling Research Group Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Karen Freudemann    513-381-4100    kfreudemann@sterlingresearch.org   
Contact: Jeanne Piccola    (513) 381-4100    jpiccola@sterlingresearch.org   
Principal Investigator: Matthew D Wenker, MD         
United States, South Carolina
Medical Research South Recruiting
Charleston, South Carolina, United States, 29407
Contact: Dani Johnson    843-766-5045    danij@medicalresearchsouth.com   
Principal Investigator: Donald P Hurley, DO         
United States, Tennessee
Vanderbilt University Medical Center, Diabetes, Endocrinology, and Metabolism Not yet recruiting
Nashville, Tennessee, United States, 37232
Contact: Cynthia k Lovell, LPN    615-936-1145    cynthia.k.lovell@vanderbilt.edu   
Contact: Margaret Survant, MT    (615) 936-1145    libby.survant@Vanderbilt.Edu   
Principal Investigator: Kevin D Niswender, MD         
Sub-Investigator: Howard Baum, MD         
Meharry Medical College Recruiting
Nashville, Tennessee, United States, 37208
Contact: Donna Skupien    615-327-5725    dskupien@mmc.edu   
Contact: Konya Williams    615-327-5528    Kwilliams2@mmc.edu   
Principal Investigator: John J Murray, MD         
Sponsors and Collaborators
NuSirt Biopharma
Investigators
Study Chair: Orville G Kolterman, MD NuSirt Biopharma
  More Information

No publications provided

Responsible Party: NuSirt Biopharma
ClinicalTrials.gov Identifier: NCT02151461     History of Changes
Other Study ID Numbers: NS-0100-01
Study First Received: May 28, 2014
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by NuSirt Biopharma:
Diabetes
Type 2 Diabetes

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 14, 2014