The Effect Of NS-0200 Versus Placebo On Hepatic Fat Content In Patients With Non Alcoholic Fatty Liver Disease
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02546609|
Recruitment Status : Completed
First Posted : September 11, 2015
Results First Posted : May 2, 2018
Last Update Posted : May 2, 2018
- Study Details
- Tabular View
- Study Results
- How to Read a Study Record
|Condition or disease||Intervention/treatment||Phase|
|NAFLD||Drug: Leu-Met-Sil 0.5 Drug: Leu-Met-Sil 1.0 Drug: Placebo||Phase 2|
This is a randomized, 16-week, placebo-controlled, double-blind study to evaluate the effect of two fixed-dose combinations of leucine, metformin and sildenafil, NS-0200 compared to placebo, on the reduction of liver fat in patients diagnosed with non-alcoholic fatty liver disease (NAFLD). Subjects meeting all the inclusion criteria and no exclusion criteria will be randomized to one of three study arms.
The primary objective of this study is to evaluate the change in hepatic fat content assessed by proton-density-fat-fraction (PDFF) employing magnetic resonance imaging (MRI) in subjects from : Screening/Visit 2 (Day-7/Week-1) to Study Termination/Visit 8 (Day 112/Week 16) receiving two fixed-dose combinations of leucine, metformin and sildenafil compared to placebo. Secondary objectives will also assess changes in serum alanine aminotransferase (ALT) activity, change in circulating cytokeratin 18, a surrogate marker of necro-inflammation, change in HbA1c, change in fasting glucose, insulin and insulin sensitivity, change in blood lipids such as cholesterol, LDL, HDL, triglycerides, and changes in in C-reactive protein. In addition this study will evaluate the safety and tolerability of NS-0200.
Patients will have two screening visits, the first to determine their eligibility based on lab tests and the second based on the percentage of hepatic fat assessed by MRI imaging. Once qualified, patients will be randomly assigned to either one of the treatment groups or the placebo control group and monitored for a total of 16 weeks. Patients will return to the clinic each month for lab tests, and routine examinations. At the conclusion of the treatment period patients will again undergo an MRI scan to examine the percentage of hepatic fat.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||91 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized, Blinded, Placebo-Controlled Study To Evaluate The Effect Fixed-Dose Leucine, Metformin, Sildenafil Combinations(NS-0200) Versus Placebo On Hepatic Fat Assessed By MRI In Non Alcoholic Fatty Liver Disease Patients|
|Study Start Date :||November 19, 2015|
|Actual Primary Completion Date :||November 30, 2016|
|Actual Study Completion Date :||January 31, 2017|
Experimental: Leu Met Sil 0.5mg
Leu-Met-Sil 0.5: 3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 0.5 mg of sildenafil.
Drug: Leu-Met-Sil 1.0
NS-200 high dose
Other Name: NS-0200-1.0
Experimental: Leu Met Sil 1.0mg
Leu-Met-Sil 1.0: 3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 1.0 mg of sildenafil.
Drug: Leu-Met-Sil 0.5
NS-0200 low dose
Other Name: NS-0200-0.5
Drug: Leu-Met-Sil 1.0
NS-200 high dose
Other Name: NS-0200-1.0
Placebo Comparator: Placebo
Placebo: 3 capsules BID containing 99% Avicel PH302 and 1% magnesium stearate (w/w)
Other Name: Control arm
- Change in Hepatic Fat [ Time Frame: Baseline, Day 112 ]To evaluate the change in hepatic fat content assessed by proton-density-fat-fraction (PDFF) employing magnetic resonance imaging (MRI).
- Change in Serum AlanineAaminotransferase (ALT) Levels [ Time Frame: Baseline, Day 112 ]Serum AlanineAminotransferase (ALT) will be examined through standard blood chemistry
- Change in Circulating Cytokeratin 18 Fragments (M30) [ Time Frame: Baseline, Day 112 ]Change in Circulating Cytokeratin 18 Fragments (M30) from Baseline to Week 16 will be examined through standard blood chemistry
- Change in Heamoglobin A1c (HbA1c) [ Time Frame: Baseline, Day 112 ]HbA1c will be examined through standard blood chemistry
- Change in Fasting Glucose [ Time Frame: Baseline, Day 112 ]Fasting glucose will be examined through standard fasting blood chemistry
- Change in Insulin [ Time Frame: Baseline, Day 112 ]Insulin levels will be examined through standard blood chemistry
- Change in Blood Lipids (Cholesterol) [ Time Frame: Baseline, Day 112 ]Lipid levels such as cholesterol will be examined by standard blood chemistry
- Change in Blood Lipids (High Density Lipoprotein:HDL) [ Time Frame: Baseline, Day 112 ]Lipid levels such as HDL will be examined by standard blood chemistry
- Change in Low Density Lipoproteins (LDL) [ Time Frame: Baseline, Day 112 ]Lipid levels such as LDL will be examined by standard blood chemistry
- Change in Triglycerides [ Time Frame: Baseline, Day 112 ]Lipid levels such as triglycerides will be examined by standard blood chemistry
- Change in C-reactive Protein [ Time Frame: Baseline, Day 112 ]CRP levels will be examined by standard blood chemistry
- Change in Insulin Sensitivity (HOMA-IR) [ Time Frame: Baseline, Day 112 ]HOMA-IR levels will be examined by standard blood chemistry
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, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years to 75 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Age 18-75 at study entry.
Is male, or female and, if female, meets all of the following criteria:
- Not breastfeeding
- Post-menopausal or negative serum pregnancy test result (human chorionic gonadotropin, beta subunit [β-hCG]) at Screening /Visit 1 (Day-14/Week-2) (not required for hysterectomized females)
- If of childbearing potential (including peri-menopausal women who have had a menstrual period within one year) must practice and be willing to continue to practice appropriate birth control (defined as a method which results in a low failure rate, i.e., less than 1% per year, when used consistently and correctly, such as double barrier methods [male condom with spermicide, with or without cervical cap or diaphragm], implants, injectables, oral contraceptives [must have been using for at least the last 3 months], some intrauterine contraceptive devices, tubal ligation, or in an established relationship with a vasectomized partner) during the entire duration of the study.
- Has been diagnosed with NAFLD via CT (positive for excess liver fat), ultrasound (positive for excess liver fat), MRI (PDFF showing > 15% liver fat) or via biopsy (showing >33% fat) within the past six months. If diagnosis was between 3 and 6 months prior to Screening, an ultrasound (positive for excess liver fat) is required prior to the Screening /Visit 1 (Day-14/Week-2) MRI.
- Has liver fat (as measured by PDFF via MRI) greater than 15% at Screening/Visit 2 (Day-7/Week-1)
- Has had ALT levels >30 U/L for men, >19 U/L for women measured within 8 weeks of enrollment
- Has an HbA1c equal to or less than 9% at Screening /Visit 1 (Day-14/Week-2)
- Has a BMI between 25kg/m2 and 40 kg/m2
- Otherwise stable health for preceding twelve weeks
- Clinical laboratory tests (hematology, clinical chemistry, and urinalysis) either normal or with abnormalities consistent with NAFLD.
Is able to read, understand, and sign the informed consent forms (ICF) and, when 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.
- Clinically significant renal dysfunction defined as a serum creatinine concentration >1.4 mg/dL (females) or >1.6 mg/dL (males) or a blood urea nitrogen concentration >45 mg/dL at screening.
Use of any of the following medications:
- Combination drugs that include Metformin
- Short acting insulins
- An alpha blocker
- Oral nitrates
- Medications associated with increased hepatic steatosis
OCT2/MATE inhibitors (e.g. cimetidine, quinidine, and pyrimethamine)
- Corticosteroids (Nasal steroids are allowed if the subject has been on a stable dose for the past 12 weeks and the dose employed does not exceed the maximal recommended dose.)
- Valproic acid
- Nucleoside analogues used for the treatment of HIV infections
- Any dietary supplement other than multi-vitamins
- Evidence of significant alcohol consumption (defined as >7 drinks/week for females and >14 drinks/week for males) within 6 months prior to randomization or presence or suspicion of other forms of chronic liver disease (e.g., cirrhosis, autoimmune hepatitis (>1:160 ANA), Wilson's disease, Hemochromatosis (Ferritin >1000 ug/L and percent iron saturation >45%), hepatitis A, B or C)
Has a clinically significant medical condition that could potentially affect study participation and/or personal well-being, as judged by the investigator, including but not limited to the following conditions:
- Unable to undergo MRI or contraindications for MRI procedure
- History of cardio- or cerebro-vascular disease event within the previous 6 months
- Requires anti-coagulation therapy
- Gastrointestinal disorders including, but not limited to, the following: pancreatitis, inflammatory bowel disease, or other diseases associated with malabsorption or persistent abdominal discomfort
- Endocrine disorders other than type 2 diabetes and hypothyroidism on stable replacement therapy
- Chronic infection (e.g., tuberculosis, human immunodeficiency virus infection, hepatitis A virus, hepatitis B virus, or hepatitis C virus)
- Neurological or psychiatric diseases that preclude valid execution of informed consent or may interfere with the subject's compliance with study procedures (e.g., major depressive disorder within the last 2 years, a history of suicidal behavior in the last 3 months)
- History of other psychiatric disorders including schizophrenia and bipolar disorder)
- Participation in a weight loss program within the past 3 months.
- Weight change ≥5% during the past month.
- History of substance abuse (including alcohol abuse as defined above) in the past 3 months or a positive screen for drugs of abuse or alcohol 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 had a serious infection, such as pneumonia in the previous 12 weeks
- Has known allergies or hypersensitivity to metformin, sildenafil or leucine
- Is an immediate family member (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study at the clinical study site, or NuSirt Biopharma.
Is employed by NuSirt Biopharma (defined as an employee, temporary contract worker, or designee responsible for the conduct of the study).
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): NCT02546609
|United States, California|
|Catalina Research Institute|
|Chino, California, United States, 91710|
|University of California San Diego|
|San Diego, California, United States, 92103|
|United States, Colorado|
|Rocky Mountain Research|
|Wheat Ridge, Colorado, United States, 80033|
|United States, Georgia|
|Atlanta Gastroenterology Associates|
|Atlanta, Georgia, United States, 30312|
|GI Specialists of Georgia|
|Marietta, Georgia, United States, 30060|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|United States, Indiana|
|Indianapolis, Indiana, United States, 46202|
|United States, North Carolina|
|University of North Carolina Chapel Hill|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Ohio|
|Cincinnati, Ohio, United States, 45246|
|United States, Tennessee|
|Premier Clinical Research|
|Clarksville, Tennessee, United States, 37043|
|Germantown, Tennessee, United States, 38138|
|Quality Medical Research|
|Nashville, Tennessee, United States, 37211|
|United States, Virginia|
|Virginia Commonwealth University|
|Richmond, Virginia, United States, 23298|
|Study Director:||Orville Kolterman, MD||NuSirt Biopharma|
|Responsible Party:||NuSirt Biopharma|
|Other Study ID Numbers:||
|First Posted:||September 11, 2015 Key Record Dates|
|Results First Posted:||May 2, 2018|
|Last Update Posted:||May 2, 2018|
|Last Verified:||April 2018|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
Non-alcoholic Fatty Liver Disease
Digestive System Diseases