To study effect of Livitol in treatment of patients diagnosed with moderate to severe non-alcoholic fatty liver.
Phase 2
Completed
- Conditions
- Fatty (change of) liver, not elsewhere classified. Ayurveda Condition: KAMALA,
- Registration Number
- CTRI/2022/04/041926
- Lead Sponsor
- Dr Reddys Laboratories
- Brief Summary
This is a randomized, prospective, multicentre,double-blind, placebo-controlled, parallel group Phase 2 study to assessefficacy and safety of Livitol among patients with moderate to severe non-alcoholicfatty liver (steatosis).
The study includes screening period (14 days) andtreatment period (24 weeks).
The study will include approximately 76 participantsat approximately 8-10 centres in India.
Prospective subjects who have ultrasonography reportconfirming moderate to severe non-alcoholic fatty liver (steatosis) will be consideredfor 14-day screening period to confirm the study eligibility. Ultrasonographypositive for moderate to severe fatty liver) is required prior to the baselineMRI-PDFF. The eligible subjects will be randomized (1:1) to receive study drug(Livitol) or placebo, and the treatment will be administered twice daily forthe duration of 24 weeks (6 months). The subjects will be evaluated at Week 4, 12and 24.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 76
Inclusion Criteria
- Age 18-65 years at study entry.
- Male, or female diagnosed with non-alcoholic fatty liver (steatosis), but if female, meets all the following criteria: a.
- Not breastfeeding b.
- Post-menopausal or negative urine pregnancy test result at Screening /Visit 1 (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.
- Patients diagnosed with moderate to severe fatty liver based on ultrasound (if ultrasound is available within 3 months of screening, it would be considered valid for screening).
- Patients with liver fat greater than 15% as measured by MRI-PDFF at Screening.
- Can read, understand, and sign the informed consent form (ICF) and communicate with the investigator, and understand and comply with protocol requirements.
Exclusion Criteria
- eGFR less than 60ml/min/1.73m2 at screening (chronic kidney disease epidemiology collaboration [CKD-EPI] formula).
- Elevation of AST or ALT greater than five times upper limit normal (ULN).
- Evidence of significant alcohol consumption (defined as more than 7 drinks/week for females and greater than 14 drinks/week for males) within 6 months prior to randomization 4.
- Body Mass Index (BMI) more than or equal to 40 kg/m2 5.
- Use of any of the following medications in the last 12 weeks prior to screening visit: a.
- Metformin greater than 2 g/day b.
- Insulins – all forms c.
- Use of sildenafil, tadalafil, vardenafil, pioglitazone, rosiglitazone, alpha blockers, oral nitrates.
- Medications associated with increased hepatic steatosis.
- Commonly used medications associated with drug induced hepatic steatosis include amiodarone, valproate, tamoxifen, methotrexate, and some chemotherapeutic and antiretroviral agents, and steroids.
- Organic Cation Transporter 2/MATE inhibitors (Includes multidrug and toxin extrusion protein 1 and multidrug and toxin extrusion protein 2 inhibitors like: i.
- Methotrexate ii.
- Tamoxifen f.
- 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) g.
- Estrogens h.
- Amiodarone i.
- Valproic acid j.
- Coumadin k.
- Isoniazide l.
- Nucleoside analogues used for the treatment of human immunodeficiency virus (HIV) infections m.
- Any dietary supplement including Vitamin E and L-Carnitine other than multi-vitamins.
- Presence or suspicion of other forms of chronic liver disease (e.g., cirrhosis, autoimmune hepatitis (greater than 1 is to 160 Anti-Nuclear Antibody ANA), Wilsons disease, Hemochromatosis (Ferritin greater than 1000 ug/L and percent iron saturation greater than 45 percent), hepatitis A, B or C), primary biliary cholangitis, primary sclerosing cholangitis, Wilsons disease, homozygous alpha 1 anti trypsin deficiency.
- 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: a.
- Unable to undergo MRI or contraindications for MRI procedure b.
- Requires anti coagulation therapy d.
- Gastrointestinal disorders including, but not limited to, the following: pancreatitis, inflammatory bowel disease, or other diseases associated with malabsorption or persistent abdominal discomfort e.
- Endocrine disorders, other than type 2 diabetes and hypothyroidism on stable replacement therapy for 3 months prior to enrolment.
- Chronic infection (e.g., tuberculosis, HIV infection, hepatitis A virus, hepatitis B virus, or hepatitis C virus) g.
- Neurological or psychiatric diseases that preclude valid execution of informed consent or may interfere with the subjects compliance with study procedures (e.g., major depressive disorder within the last 2 years, a history of suicidal behaviour in the last 3 months).
- This will be based on investigator’s opinion and does not need formal psychological screening.
- History of other psychiatric disorders including schizophrenia and bipolar disorder only through clinical history and does not require a psychological screening.
- Participation in a weight loss program within the past 3 months and /or weight change greater than or equal to 5 percent during the past month.
- History of substance abuse (including alcohol abuse as defined above) in the past 3 months 10.
- 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 acute infection, such as pneumonia in the previous 12 weeks 13.
- Prior or planned (during the study period) bariatric surgery (e.g., gastroplasty, sleeve gastrectomy and roux-en-Y gastric bypass).
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Hepatic Fat content Baseline, Week 24
- Secondary Outcome Measures
Name Time Method 1. To evaluate the change from baseline in fatty liver grading using the 4 ultrasound criteria or signs 2. To evaluate the change in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and
Trial Locations
- Locations (9)
Citizen Hospital
🇮🇳Bangalore, KARNATAKA, India
M V Hospital and Research Centre
🇮🇳Lucknow, UTTAR PRADESH, India
N R R Hospital
🇮🇳Bangalore, KARNATAKA, India
ORIION Citicare Super-Speciality Hospital
🇮🇳Aurangabad, MAHARASHTRA, India
Oyster and Pearl Hospital
🇮🇳Pune, MAHARASHTRA, India
Rajalakshmi Hospital
🇮🇳Bangalore, KARNATAKA, India
SAMVEDNA HOSPITAL
🇮🇳Varanasi, UTTAR PRADESH, India
SGG Hospital
🇮🇳Vadodara, GUJARAT, India
Surat Institute of Digestive Sciences, A unit of SIDS healthcare Pvt Ltd
🇮🇳Surat, GUJARAT, India
Citizen Hospital🇮🇳Bangalore, KARNATAKA, IndiaDr Ambanna GowdaPrincipal investigator9980107723dr.ambanagowda@gmail.com