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NAFLDPhase 2NCT02546609

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

A Phase 2 study testing Leu-Met-Sil 0.5 and Leu-Met-Sil 1.0 in people with NAFLD, run by NuSirt Biopharma at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
NAFLD
What is being tested?
Leu-Met-Sil 0.5 and Leu-Met-Sil 1.0
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
91 participants
Where
13 sitesUnited States
Study dates
19 Nov 2015to 31 Jan 2017
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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 14Show fewer
  • 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.
  • -

Who cannot join

  • 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
Show all 45Show fewer
  • 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).
  • -

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites

  • Atlanta Gastroenterology Associates

    Atlanta, Georgia, 30312

  • University of North Carolina Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Northwestern University

    Chicago, Illinois, 60611

  • Catalina Research Institute

    Chino, California, 91710

  • Sterling Research

    Cincinnati, Ohio, 45246

  • Premier Clinical Research

    Clarksville, Tennessee, 37043

  • Gastro One

    Germantown, Tennessee, 38138

  • Indiana University

    Indianapolis, Indiana, 46202

  • GI Specialists of Georgia

    Marietta, Georgia, 30060

  • Quality Medical Research

    Nashville, Tennessee, 37211

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • University of California San Diego

    San Diego, California, 92103

  • Rocky Mountain Research

    Wheat Ridge, Colorado, 80033

Other trials in United States

About this study

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

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.

Read the 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.

Conditions
NAFLD
Being tested
Leu-Met-Sil 0.5, Leu-Met-Sil 1.0, Placebo
Medical subject headings
Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Leu-Met-Sil 0.5Drug

    Also called NS-0200-0.5

    NS-0200 low dose

  • Leu-Met-Sil 1.0Drug

    Also called NS-0200-1.0

    NS-200 high dose

  • PlaceboDrug

    Also called Control arm

    Placebo

Study groups in NCT02546609
Study groupRoleWhat they receive
Leu Met Sil 0.5mgExperimentalLeu-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.
Receives: Drug: Leu-Met-Sil 1.0
Leu Met Sil 1.0mgExperimentalLeu-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.
Receives: Drug: Leu-Met-Sil 0.5; Drug: Leu-Met-Sil 1.0
PlaceboPlacebo comparatorPlacebo: 3 capsules BID containing 99% Avicel PH302 and 1% magnesium stearate (w/w)
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Hepatic Fat

    To evaluate the change in hepatic fat content assessed by proton-density-fat-fraction (PDFF) employing magnetic resonance imaging (MRI).

    Measured: Baseline, Day 112

Secondary outcomes (11)

  1. Change in Serum AlanineAaminotransferase (ALT) Levels

    Serum AlanineAminotransferase (ALT) will be examined through standard blood chemistry

    Measured: Baseline, Day 112

  2. Change in Circulating Cytokeratin 18 Fragments (M30)

    Change in Circulating Cytokeratin 18 Fragments (M30) from Baseline to Week 16 will be examined through standard blood chemistry

    Measured: Baseline, Day 112

  3. Change in Heamoglobin A1c (HbA1c)

    HbA1c will be examined through standard blood chemistry

    Measured: Baseline, Day 112

  4. Change in Fasting Glucose

    Fasting glucose will be examined through standard fasting blood chemistry

    Measured: Baseline, Day 112

  5. Change in Insulin

    Insulin levels will be examined through standard blood chemistry

    Measured: Baseline, Day 112

  6. Change in Blood Lipids (Cholesterol)

    Lipid levels such as cholesterol will be examined by standard blood chemistry

    Measured: Baseline, Day 112

  7. Change in Blood Lipids (High Density Lipoprotein:HDL)

    Lipid levels such as HDL will be examined by standard blood chemistry

    Measured: Baseline, Day 112

  8. Change in Low Density Lipoproteins (LDL)

    Lipid levels such as LDL will be examined by standard blood chemistry

    Measured: Baseline, Day 112

  9. Change in Triglycerides

    Lipid levels such as triglycerides will be examined by standard blood chemistry

    Measured: Baseline, Day 112

  10. Change in C-reactive Protein

    CRP levels will be examined by standard blood chemistry

    Measured: Baseline, Day 112

  11. Change in Insulin Sensitivity (HOMA-IR)

    HOMA-IR levels will be examined by standard blood chemistry

    Measured: Baseline, Day 112

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Sep 2015 (estimated)
  2. Study start19 Nov 2015
  3. Primary completion30 Nov 2016
  4. Study completion31 Jan 2017

Resources

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
91 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02546609
Sponsor's protocol ID
NS-0200-01
Status last verified
Apr 2018
First submitted
3 Sep 2015
Last updated
2 May 2018
Data monitoring committee
No
Individual data sharing
No

Publications

  • Nedrud MA, Chaudhry M, Middleton MS, Moylan CA, Lerebours R, Luo S, Farjat A, Guy C, Loomba R, Abdelmalek MF, Sirlin CB, Bashir MR. MRI Quantification of Placebo Effect in Nonalcoholic Steatohepatitis Clinical Trials. Radiology. 2023 Mar;306(3):e220743. doi: 10.1148/radiol.220743. Epub 2022 Nov 1.

    PubMed 36318027

  • Zemel MB, Kolterman O, Rinella M, Vuppalanchi R, Flores O, Barritt AS 4th, Siddiqui M, Chalasani N. Randomized Controlled Trial of a Leucine-Metformin-Sildenafil Combination (NS-0200) on Weight and Metabolic Parameters. Obesity (Silver Spring). 2019 Jan;27(1):59-67. doi: 10.1002/oby.22346.

    PubMed 30569637

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Leu-Met-Sil 0.5 and Leu-Met-Sil 1.0 in people with NAFLD, run by NuSirt Biopharma at 13 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 14 inclusion and 45 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 2 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 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. Some participants in this study may receive a placebo. 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 2 May 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 in Hepatic Fat (time frame: Baseline, Day 112). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02546609, which also lists 2 linked publications.

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 2 May 2018.

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