Type 2 Diabetes MellitusPhase 2NCT02151461
Dose Comparisons of Leucine-Metformin Combinations on Blood Glucose Levels In Type 2 Diabetic Patients
A Phase 2 study testing Low Metformin, Metformin and Mid Metformin in people with Type 2 Diabetes Mellitus, run by NuSirt Biopharma at 9 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- Low Metformin, Metformin and Mid Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 9 sitesUnited States
- Study dates
- Jul 2014to Jan 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
River Birch Research Alliance
Blue Ridge, Georgia, 30513
Medical Research South
Charleston, South Carolina, 29407
Catalina Research Institute
Chino, California, 91710
Streling Research Group
Cincinnati, Ohio, 45219
Meharry Medical College
Nashville, Tennessee, 37208
Vanderbilt University Medical Center, Diabetes, Endocrinology, and Metabolism
Nashville, Tennessee, 37232
Palm Beach Research
Palm Beach, Florida, 33409
Meridian Research
Savannah, Georgia, 31406
Meridien Research
Tampa, Florida, 33606
About this study
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
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.
Read the 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
- Being tested
- Low Metformin, Metformin, Mid Metformin, High Metformin
- Keywords
- Diabetes, Type 2 Diabetes
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low MetforminDrug
Also called Metformin, Leucine, L-Leucine
1100 mg L Leucine in combination with 125 mg of Metformin BID
MetforminDrug
500 mg metformin BID until day 14 with dose escalation at day 14 to 850 mg metformin BID
Mid MetforminDrug
Also called Metformin, Leucine, L-Leucine
1100 mg of Leucine in combination with 250 mg Metformin BID
High MetforminDrug
Also called Metformin, Leucine, L-Leucine
1100 mg of Leucine in combination with 500 mg Metformin BID
| Study group | Role | What they receive |
|---|---|---|
| Low Metformin | Experimental | 3 capsules BID with each capsule containing 366.7 mg L-Leucine and 41.7 mg of metformin Receives: Drug: Low Metformin |
| Mid Metformin | Experimental | 3 capsules BID with each capsule containing 366.7 mg L-Leucine and 83.3 mg of metformin Receives: Drug: Mid Metformin |
| High Metformin | Experimental | 3 capsules BID with each capsule containing 366.7 mg L-Leucine and 166.7 mg of metformin Receives: Drug: High Metformin |
| Metformin Monotherapy | Experimental | 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. Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Day 28 in Absolute Plasma Glucose Area Under the Curve (AUC) 0-3hr
The primary endpoint for NS 0100 01 was the absolute plasma glucose AUC (0-3 hr) change from Day 1 to Day 28.
Measured: 0, 15min, 30min, 45min, 1hr, 1.5hrs, 2hrs, 2.5hrs and 3 hrs
Secondary outcomes (7)
Change From Baseline to Day 28 in Incremental Plasma Glucose Area Under the Curve (AUC)
The baseline incremental (baseline-subtracted) glucose AUC0-3h was evaluated for treatment differences at baseline.
Measured: Baseline, Day 28
Change in Fasting Plasma Glucose
Change in fasting plasma glucose for the fixed dose leucine and metformin combination treatments A, B and C was evaluated.
Measured: Baseline, Day 28
Change in Hemoglobin A1c (HbA1c)
Changes in HbA1c which is a marker of long-term glucose control was assessed.
Measured: Baseline, Day 28
Change in Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR)
Effect on insulin sensitivity across fixed-dose leucine and metformin combination treatments or the standard metformin reference treatment.
Measured: Baseline, Day 28
Change In 7-Point Glucose Profiles
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.
Measured: Baseline, Day 7, Day 21, Day 28
Plasma Insulin Absolute and Incremental Meal Tolerance Test Area Under the Curve (AUC) 0-2hr
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.
Measured: Baseline,Day 28
Change From Baseline to Day 28 in Fasting Plasma Insulin Concentration
Effect on fasting plasma insulin concentrations across fixed-dose leucine and metformin combination treatments or the standard metformin reference treatment was evaluated.
Measured: Baseline, Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2014 (estimated)
- Study startJul 2014
- Primary completionAug 2015
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- NuSirt Biopharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Orville G Kolterman, MD, Study chair, NuSirt Biopharma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02151461
- Sponsor's protocol ID
- NS-0100-01
- Status last verified
- Feb 2018
- First submitted
- 28 May 2014
- Last updated
- 27 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02151461
- Acronym / sponsor ID
- NS-0100-01
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- Diabetes, Type 2 Diabetes
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- NuSirt BiopharmaIndustry (pharma, biotech, devices)
- Study start
- Jul 2014
- Primary completion
- Aug 2015 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 30 May 2014 (estimated)
- Results
- Posted 5 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Low Metformin | Experimental | Drug: Low Metformin3 capsules BID with each capsule containing 366.7 mg L-Leucine and 41.7 mg of metformin |
| Mid Metformin | Experimental | Drug: Mid Metformin3 capsules BID with each capsule containing 366.7 mg L-Leucine and 83.3 mg of metformin |
| High Metformin | Experimental | Drug: High Metformin3 capsules BID with each capsule containing 366.7 mg L-Leucine and 166.7 mg of metformin |
| Metformin Monotherapy | Experimental | Drug: Metformin3 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low MetforminAlso: Metformin, Leucine, L-Leucine1100 mg L Leucine in combination with 125 mg of Metformin BID | Drug | Low Metformin |
| Metformin500 mg metformin BID until day 14 with dose escalation at day 14 to 850 mg metformin BID | Drug | Metformin Monotherapy |
| Mid MetforminAlso: Metformin, Leucine, L-Leucine1100 mg of Leucine in combination with 250 mg Metformin BID | Drug | Mid Metformin |
| High MetforminAlso: Metformin, Leucine, L-Leucine1100 mg of Leucine in combination with 500 mg Metformin BID | Drug | High Metformin |
Primary outcome
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.
7 secondary outcomes
Change From Baseline to Day 28 in Incremental Plasma Glucose Area Under the Curve (AUC)
Time frame: Baseline, Day 28
Change in Fasting Plasma Glucose
Time frame: Baseline, Day 28
Change in Hemoglobin A1c (HbA1c)
Time frame: Baseline, Day 28
Change in Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR)
Time frame: Baseline, Day 28
Change In 7-Point Glucose Profiles
Time frame: Baseline, Day 7, Day 21, Day 28
Plasma Insulin Absolute and Incremental Meal Tolerance Test Area Under the Curve (AUC) 0-2hr
Time frame: Baseline,Day 28
Change From Baseline to Day 28 in Fasting Plasma Insulin Concentration
Time frame: Baseline, Day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Orville G Kolterman, MD study chair
NuSirt Biopharma
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Low Metformin, Metformin and Mid Metformin in people with Type 2 Diabetes Mellitus, run by NuSirt Biopharma at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2018.