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Trial record 13 of 350 for:    hepatic steatosis AND fat AND Nonalcoholic Fatty Liver

The Effect Of NS-0200 Versus Placebo On Hepatic Fat Content In Patients With Non Alcoholic Fatty Liver Disease

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ClinicalTrials.gov Identifier: NCT02546609
Recruitment Status : Completed
First Posted : September 11, 2015
Results First Posted : May 2, 2018
Last Update Posted : May 2, 2018
Sponsor:
Information provided by (Responsible Party):
NuSirt Biopharma

Tracking Information
First Submitted Date  ICMJE September 3, 2015
First Posted Date  ICMJE September 11, 2015
Results First Submitted Date  ICMJE February 26, 2018
Results First Posted Date  ICMJE May 2, 2018
Last Update Posted Date May 2, 2018
Study Start Date  ICMJE November 19, 2015
Actual Primary Completion Date November 30, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 3, 2018)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: September 9, 2015)
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 History Complete list of historical versions of study NCT02546609 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 3, 2018)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: September 9, 2015)
  • Change in serum alanine aminotransferase (ALT) [ Time Frame: Baseline, Day 112 ]
    ALT will be examined through standard blood chemistry
  • Change in circulating cytokeratin 18 [ Time Frame: Baseline, Day 112 ]
    K18 will be examined through standard blood chemistry
  • Change in 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 and insulin sensitivity [ Time Frame: Baseline, Day 112 ]
    Insulin levels will be examined through standard blood chemistry
  • Change in blood lipids [ Time Frame: Baseline, Day 112 ]
    Lipid levels such as cholesterol LDL, HDL, 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
  • Number of participants with treatment related adverse events [ Time Frame: Baseline, Day 112 ]
    Patients will be monitored and asked about any adverse events or problems they encounter as a result of the study drug
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effect Of NS-0200 Versus Placebo On Hepatic Fat Content In Patients With Non Alcoholic Fatty Liver Disease
Official Title  ICMJE 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
Brief Summary The goal of this study is to determine if NS-0200 can reduce the amount of liver fat in patients diagnosed with non-alcoholic fatty liver disease (NAFLD). This study will compare two doses of NS-0200 to placebo in NAFLD patients.
Detailed Description

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE NAFLD
Intervention  ICMJE
  • 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
  • Drug: Placebo
    Placebo
    Other Name: Control arm
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Leu-Met-Sil 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.
    Interventions:
    • Drug: Leu-Met-Sil 0.5
    • Drug: Leu-Met-Sil 1.0
  • Placebo Comparator: Placebo
    Placebo: 3 capsules BID containing 99% Avicel PH302 and 1% magnesium stearate (w/w)
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 13, 2017)
91
Original Estimated Enrollment  ICMJE
 (submitted: September 9, 2015)
90
Actual Study Completion Date  ICMJE January 31, 2017
Actual Primary Completion Date November 30, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age 18-75 at study entry.
  2. Is male, or female and, if female, meets all of the following criteria:

    1. Not breastfeeding
    2. 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)
    3. 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.
  3. 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.
  4. Has liver fat (as measured by PDFF via MRI) greater than 15% at Screening/Visit 2 (Day-7/Week-1)
  5. Has had ALT levels >30 U/L for men, >19 U/L for women measured within 8 weeks of enrollment
  6. Has an HbA1c equal to or less than 9% at Screening /Visit 1 (Day-14/Week-2)
  7. Has a BMI between 25kg/m2 and 40 kg/m2
  8. Otherwise stable health for preceding twelve weeks
  9. Clinical laboratory tests (hematology, clinical chemistry, and urinalysis) either normal or with abnormalities consistent with NAFLD.
  10. 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.

    -

Exclusion Criteria:

  1. 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.
  2. Use of any of the following medications:

    1. Metformin
    2. Combination drugs that include Metformin
    3. Sildenafil
    4. Tadalafil
    5. Vardenafil
    6. Pioglitazone
    7. Rosiglitazone
    8. Short acting insulins
    9. An alpha blocker
    10. Oral nitrates
    11. Medications associated with increased hepatic steatosis
    12. Insulins
    13. 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
    14. Any dietary supplement other than multi-vitamins
  3. 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)
  4. 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:

    1. Unable to undergo MRI or contraindications for MRI procedure
    2. History of cardio- or cerebro-vascular disease event within the previous 6 months
    3. Requires anti-coagulation therapy
    4. Gastrointestinal disorders including, but not limited to, the following: pancreatitis, inflammatory bowel disease, or other diseases associated with malabsorption or persistent abdominal discomfort
    5. Endocrine disorders other than type 2 diabetes and hypothyroidism on stable replacement therapy
    6. Chronic infection (e.g., tuberculosis, human immunodeficiency virus infection, hepatitis A virus, hepatitis B virus, or hepatitis C virus)
    7. 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)
    8. History of other psychiatric disorders including schizophrenia and bipolar disorder)
  5. Participation in a weight loss program within the past 3 months.
  6. Weight change ≥5% during the past month.
  7. 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.
  8. Has received any investigational drug within 3 months of Screening.
  9. Has donated blood within 3 months before Screening or is planning to donate blood during the study.
  10. Has had a serious infection, such as pneumonia in the previous 12 weeks
  11. Has known allergies or hypersensitivity to metformin, sildenafil or leucine
  12. 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.
  13. Is employed by NuSirt Biopharma (defined as an employee, temporary contract worker, or designee responsible for the conduct of the study).

    -

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02546609
Other Study ID Numbers  ICMJE NS-0200-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party NuSirt Biopharma
Study Sponsor  ICMJE NuSirt Biopharma
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Orville Kolterman, MD NuSirt Biopharma
PRS Account NuSirt Biopharma
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP