The Effect Of NS-0200 Versus Placebo On Hepatic Fat Content In Patients With Non Alcoholic Fatty Liver Disease
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
研究概览
详细说明
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.
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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California
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Chino、California、美国、91710
- Catalina Research Institute
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San Diego、California、美国、92103
- University of California San Diego
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Colorado
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Wheat Ridge、Colorado、美国、80033
- Rocky Mountain Research
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Georgia
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Atlanta、Georgia、美国、30312
- Atlanta Gastroenterology Associates
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Marietta、Georgia、美国、30060
- GI Specialists of Georgia
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Illinois
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Chicago、Illinois、美国、60611
- Northwestern University
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Indiana
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Indianapolis、Indiana、美国、46202
- Indiana University
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North Carolina
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Chapel Hill、North Carolina、美国、27599
- University of North Carolina Chapel Hill
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Ohio
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Cincinnati、Ohio、美国、45246
- Sterling Research
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Tennessee
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Clarksville、Tennessee、美国、37043
- Premier Clinical Research
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Germantown、Tennessee、美国、38138
- Gastro One
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Nashville、Tennessee、美国、37211
- Quality Medical Research
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Virginia
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Richmond、Virginia、美国、23298
- Virginia Commonwealth University
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- 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.
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Exclusion Criteria:
- 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:
- Metformin
- Combination drugs that include Metformin
- Sildenafil
- Tadalafil
- Vardenafil
- Pioglitazone
- Rosiglitazone
- Short acting insulins
- An alpha blocker
- Oral nitrates
- Medications associated with increased hepatic steatosis
- Insulins
OCT2/MATE inhibitors (e.g. cimetidine, quinidine, and pyrimethamine)
- Methotrexate
- Tamoxifen
- 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.)
- Estrogens
- Amiodarone
- Valproic acid
- Coumadin
- Isoniazide
- 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).
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学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:四人间
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的: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.
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NS-200 high dose
其他名称:
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实验性的: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.
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NS-200 high dose
其他名称:
NS-0200 low dose
其他名称:
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安慰剂比较:Placebo
Placebo: 3 capsules BID containing 99% Avicel PH302 and 1% magnesium stearate (w/w)
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安慰剂
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Change in Hepatic Fat
大体时间:Baseline, Day 112
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To evaluate the change in hepatic fat content assessed by proton-density-fat-fraction (PDFF) employing magnetic resonance imaging (MRI).
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Baseline, Day 112
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Change in Serum AlanineAaminotransferase (ALT) Levels
大体时间:Baseline, Day 112
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Serum AlanineAminotransferase (ALT) will be examined through standard blood chemistry
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Baseline, Day 112
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Change in Circulating Cytokeratin 18 Fragments (M30)
大体时间:Baseline, Day 112
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Change in Circulating Cytokeratin 18 Fragments (M30) from Baseline to Week 16 will be examined through standard blood chemistry
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Baseline, Day 112
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Change in Heamoglobin A1c (HbA1c)
大体时间:Baseline, Day 112
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HbA1c will be examined through standard blood chemistry
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Baseline, Day 112
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Change in Fasting Glucose
大体时间:Baseline, Day 112
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Fasting glucose will be examined through standard fasting blood chemistry
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Baseline, Day 112
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Change in Insulin
大体时间:Baseline, Day 112
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Insulin levels will be examined through standard blood chemistry
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Baseline, Day 112
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Change in Blood Lipids (Cholesterol)
大体时间:Baseline, Day 112
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Lipid levels such as cholesterol will be examined by standard blood chemistry
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Baseline, Day 112
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Change in Blood Lipids (High Density Lipoprotein:HDL)
大体时间:Baseline, Day 112
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Lipid levels such as HDL will be examined by standard blood chemistry
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Baseline, Day 112
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Change in Low Density Lipoproteins (LDL)
大体时间:Baseline, Day 112
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Lipid levels such as LDL will be examined by standard blood chemistry
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Baseline, Day 112
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Change in Triglycerides
大体时间:Baseline, Day 112
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Lipid levels such as triglycerides will be examined by standard blood chemistry
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Baseline, Day 112
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Change in C-reactive Protein
大体时间:Baseline, Day 112
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CRP levels will be examined by standard blood chemistry
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Baseline, Day 112
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Change in Insulin Sensitivity (HOMA-IR)
大体时间:Baseline, Day 112
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HOMA-IR levels will be examined by standard blood chemistry
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Baseline, Day 112
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合作者和调查者
调查人员
- 研究主任:Orville Kolterman, MD、NuSirt Biopharma
出版物和有用的链接
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
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Ann & Robert H Lurie Children's Hospital of Chicago尚未招聘
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Centre Hospitalier Universitaire de Nice招聘中
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Universidad VeracruzanaNational Council of Science and Technology, Mexico; Instituto de Seguridad y Servicios Sociales...完全的
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Mila (bMotion Technologies)完全的
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Universidad Autonoma de MadridCentro Universitario La Salle完全的