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A Pilot Study to Assess the Safety of Oral Insulin in Patients With Nonalcolholic Steatohepatitis (NASH)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02653300
Recruitment Status : Recruiting
First Posted : January 12, 2016
Last Update Posted : December 10, 2018
Hadassah Medical Organization
Information provided by (Responsible Party):
Oramed, Ltd.

Brief Summary:
This is an open, pilot study using the oral ORMD-0801 insulin formulation in patients with NASH and confirmed type 2 DM or pre-diabetes. The study will consist of a Screening, placebo run-in, treatment phase and end-of-study phase.

Condition or disease Intervention/treatment Phase
Non-Alcoholic Steatohepatitis (NASH) Type2 Diabetes Mellitus Biological: Oral Insulin Phase 2

Detailed Description:

This exploratory study will first enroll 10 patients with NASH and type 2 DM, to evaluate the safety of oral insulin and to measure the change in liver fat content.

At the completion of their 4-week follow-up period, results will be presented to the Helsinki Committee. Following approval, an additional 20 patients will be enrolled. The size of the study population was determined by the investigator (with literature review) to be sufficient to show trends of reducing liver fat content by analysis of MRI PDFF (MRI-Proton Density Fat Fraction) images, the FibroMax™ Test and Fibroscan® including Controlled Attenuation Parameter (CAP™). CAP™ is a measure of the ultrasound attenuation to quantify steatosis in the liver.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Pilot Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics and Potential of Oral Insulin to Reduce Liver Fat Content and Fibrosis in Patients With Nonalcolholic Steatohepatitis (NASH)
Actual Study Start Date : September 20, 2018
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : April 2019

Arm Intervention/treatment
Experimental: Oral Insulin
Biological: Oral Insulin
all patients will receive treatment regimen of a soft gel capsule of ORMD-0801.

Primary Outcome Measures :
  1. Change in MRI-Proton Density Fat Fraction (MRI-PDFF) [ Time Frame: Two timepoints: Baseline (week 0) and Week 12 ]
    Change in MRI-Proton Density Fat Fraction and percentage change from baseline to week 12

Secondary Outcome Measures :
  1. Change in Transient Elastography Measurement (Fibroscan) [ Time Frame: Two timepoints: Baseline (week 0) and Week 12 ]
    Change in the transient elasticity, measured in kPA (kilo Pascal), and percent change from baseline.

  2. Change in Fibrosis score (FibroMax) [ Time Frame: Two timepoints: Baseline (week 0) and Week 12 ]
    Change in the fibrosis score (severity scale of liver fibrosis) and percentage change from baseline to week 12.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Known type 2 DM according to American Diabetic Association (one of the three needed): Fasting Plasma Glucose ≥126 mg/dl or 2h postprandial (PG) following 75g OGTT ≥ 200 mg/dl or HbA1C > 5.7% or on treatment with metformin
  • Abdominal ultrasound (US) proven fatty liver performed within 6 months before randomization, confirmed by central US.
  • Fat concentration in the liver of S2 (moderate steatosis, 6-32% hepatocytes with steatosis) or more as measured by Fibromax.
  • Signature of the written informed consent.
  • Negative pregnancy test at study entry for females of child bearing potential.
  • Females must have a negative urine pregnancy test result at screening, prior to the start of the run-in period, and at initiation of active dosing. A negative urine and serum pregnancy test must be obtained prior to active dosing. Males and females of childbearing potential must use two methods of contraception.
  • Females of non-childbearing potential are defined as postmenopausal who a) had more than 24 months since last menstrual cycle with menopausal levels of FSH, b) who are surgically menopausal.
  • For hypertensive patients, hypertension must be controlled by stable dose of anti-hypertensive medication for at least 2 months prior to screening with BP < 150/<95 mmHg
  • Patients previously treated with vitamin E (>400IU/day).
  • Glycaemia must be controlled (Glycosylated Hemoglobin A1C ≤9%) while any HbA1C increment should not exceed 1% during 6 months prior to enrolment).

Exclusion Criteria:

  • Patients with active (acute or chronic) liver disease other than NASH (e.g. viral hepatitis, genetic hemochromatosis, Wilson disease, alpha 1antitripsin deficiency, alcohol liver disease, drug induced liver disease) at the time of randomization.
  • ALT or AST ≥ 2 times ULN
  • Abnormal synthetic liver function (serum albumin ≤3.5gm%, INR >1.3).
  • Known alcohol and/or any other drug abuse or dependence in the last five years.
  • Weight >120 Kg
  • Known history or presence of clinically significant cardiovascular, gastrointestinal, metabolic (other than diabetes mellitus), neurologic, pulmonary, endocrine, psychiatric, neoplastic disorder or nephrotic syndrome.
  • History or presence of any disease or condition known to interfere with the absorption, distribution, metabolism or excretion of drugs including bile salt metabolites (e.g. inflammatory bowel disease (IBD), previous intestinal (ileal or colonic) operation, chronic pancreatitis, celiac disease or previous vagotomy.
  • Weight loss of more than 5% within 6 months prior to randomization.
  • History of bariatric surgery.
  • Uncontrolled blood pressure BP ≥150/95.
  • Non type 2 DM (type I, endocrinopathy, genetic syndromes etc).
  • Patients with HIV.
  • Daily alcohol intake >20 g/day for women and >30 g/day for men.
  • Treatment anti-diabetic medications other than metformin, such as DPP-4 inhibitors, GLP-1 receptor agonists, TZDs, etc.
  • Metformin, Fibrates, Statins, not provided on a stable dose in the last 6 months.
  • Patients who are treated with Valproic acid, Tamoxifen, Methotrexate, Amiodaron.
  • Chronic treatment with antibiotics (e.g. Rifaximin).
  • Homeopathic and/or Alternative treatments.
  • Uncontrolled hypothyroidism defined as Thyroid Stimulating Hormone >2X the upper limit of normal (UNLN).
  • Patients with renal dysfunction: eGFR< 40 ml/min.
  • Unexplained serum creatinine phosphokinase

Information from the National Library of Medicine

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 identifier (NCT number): NCT02653300

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Contact: Rifaat Safadi, M.D. 972 (0) 2 6777337
Contact: Miriam Kidron, Ph.D. 972-(0) 2-566-0001

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Hadassah Medical Center Recruiting
Jerusalem, Israel
Contact: Rifat Safadi, M. D.    972 (0) 2 6777337   
Contact: Rifat Safadi, M.D.    972 (0)2 6777337   
Sponsors and Collaborators
Oramed, Ltd.
Hadassah Medical Organization
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Principal Investigator: Rifaat Safadi, M.D. Hadassah Medical Center

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Responsible Party: Oramed, Ltd. Identifier: NCT02653300     History of Changes
Other Study ID Numbers: ORA-D-N01
First Posted: January 12, 2016    Key Record Dates
Last Update Posted: December 10, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Liver Diseases
Digestive System Diseases
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs