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Effect of Dulaglutide on Liver Fat in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease (D-LIFT)

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ClinicalTrials.gov Identifier: NCT03590626
Recruitment Status : Recruiting
First Posted : July 18, 2018
Last Update Posted : March 11, 2019
Sponsor:
Information provided by (Responsible Party):
Dr Mohammad Shafi Kuchay, Medanta, The Medicity, India

Brief Summary:
This D-LIFT (Effect of dulaglutide on Liver Fat) trial is an investigator initiated, prospective, open label, randomized clinical study to examine the effect of dulaglutide 0.75 mg subcutaneously weekly for 4 weeks, followed by 1.5 mg weekly for 20 weeks when included in the standard treatment for type 2 diabetes vs. standard treatment for type 2 diabetes (minus dulaglutide) in patients with type 2 diabetes and NAFLD. Hepatic steatosis (intracellular fat accumulation in hepatocytes) will be measured by MRI-PDFF, a validated quantitative biomarker for liver fat. The study will be conducted according to the CONSORT guidelines. The patient population for the trial will be derived from Medanta-The Medicity Hospital endocrine out-patient clinic, who would primarily visit for management of type 2 diabetes and other co-morbidities. The study will be conducted in Medanta-The Medicity Hospital, Gurugram, Haryana, which is a tertiary care center in North India. Patients deemed eligible will be screened for the trial. The clinical trial protocol will be presented for approval to the institutional ethics review board. Informed written consent will be obtained from all the participants before enrolment into the study.

Condition or disease Intervention/treatment Phase
Non Alcoholic Fatty Liver Disease Type2 Diabetes Mellitus Drug: Dulaglutide Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: will randomize the patients into either dulaglutide group or control group in a 1:1 ratio using computer-generated numbers
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Dulaglutide on Liver Fat in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial
Actual Study Start Date : January 1, 2019
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : September 2020


Arm Intervention/treatment
Experimental: Dulaglutide group
receive dulaglutide 0.75 mg weekly for 4 weeks followed by 1.5 mg weekly for 20 weeks plus standard treatment for type 2 diabetes
Drug: Dulaglutide
0.75 mg weekly for 4 weeks followed by 1.5 mg weekly for 20 weeks

No Intervention: Control group
receive standard treatment for type 2 diabetes and up titration of treatment will be done by anti-diabetic medicines other than the GLP-1 receptor agonist



Primary Outcome Measures :
  1. Change in liver fat [ Time Frame: Baseline to 24 weeks ]
    change in liver fat quantified by MRI-PDFF in colocalized regions of interest (ROI) within each of the nine liver segments


Secondary Outcome Measures :
  1. Change in Biochemical Markers [ Time Frame: Basline to 24 weeks ]
    change in serum AST levels

  2. Change in Fibroscan Parameters [ Time Frame: Basline to 24 weeks ]
    Change in liver stiffness measurement (LSM) in kPa

  3. Change in Fibroscan Parameters [ Time Frame: Basline to 24 weeks ]
    Change in Controlled Attenuation Parameter (CAP) in dB/m

  4. change in cardiometabolic markers [ Time Frame: Basline to 24 weeks ]
    change in cardiometabolic markers namely IL-1, TNF-alpha, hs-CRP, leptin, adiponectin and homocysteine and fibrosis markers

  5. Change in Biochemical Markers [ Time Frame: Baseline to 24 weeks ]
    Change in serum ALT levels

  6. Change in Biochemical Markers [ Time Frame: Baseline to 24 weeks ]
    change in serum GGT levels



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Ages Eligible for Study:   20 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. A man or woman, 20 years of age or above with the diagnosis of type 2 diabetes for at least 3 months who meets all of the following two criteria:

    1. On standard anti-diabetic agents (metformin, DPP-4 inhibitors, sulphonylureas or insulin, in any combination) with an HbA1c of ≤ 7.0% and ≥10.0% (≤53 and ≥86 mmol/mol) at screening
    2. Have documented hepatic steatosis (MRI-PDFF >6%) on screening MRI-PDFF
  2. Subjects must be medically stable on the basis of medical history, physical examination and laboratory investigations.
  3. Subjects must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
  4. Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose of the study and are willing to participate in the study

Exclusion Criteria:

  1. History of diabetic ketoacidosis, type 1 diabetes, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy.
  2. History of brittle or labile glycemic control, with widely varying glucose measurements by FPG or SMBG such that stable glucose control over the treatment period would be unlikely.
  3. History of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-V) criteria within 3 years before Screening, or an Alcohol Use Disorders Identification Test (AUDIT) with a score ≥8, or alcohol consumption of more than 20 g per day in the case of women and more than 30 g per day in the case of men for at least three consecutive months during the previous 5 years.
  4. Thyroid stimulating hormone (TSH) value that is either < 0.45 mIU/L or >10 mIU/L at Screening.

    Note: Subjects on thyroid hormone replacement therapy must be on a stable dose and dosing regimen for at least 4 weeks prior to enrollment.

  5. Use of a PPARγ agonist [e.g., a thiazolidinedione (pioglitazone], an SGLT2 inhibitor (e.g., canagliflozin, empagliflozin) or another GLP-1 receptor agonist (e.g., liraglutide) within 24 weeks before the enrollment.
  6. BMI ≥23 kg/m2 or ≤40 kg/m2.
  7. Ongoing eating disorder, or a significant weight loss or weight gain within 12 weeks before the Screening visit, defined as an increase or decrease of 5% in body weight based upon clinic-based measurement or, if not available, based on subject's report.
  8. Use of weight loss medication (prescription and/or over-the-counter) within 3 months prior to Screening or have participated in a weight loss/diet program within 12 months prior to Screening.
  9. Renal disease that required treatment with immunosuppressive therapy or a history of dialysis or renal transplant.
  10. Myocardial infarction, unstable angina, pulmonary hypertension, revascularisation procedure (e.g., stent or bypass graft surgery), or cerebrovascular accident within 3 months before Screening, or revascularisation procedure is planned, or subject has a history of New York Heart Association (NYHA) Class III-IV cardiac disease.
  11. History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening.
  12. Use of vitamin E within 3 months before screening.
  13. History of prior bariatric (e.g., Roux-en-Y gastric bypass) or other major upper gastrointestinal surgical procedure (including gastric resection).
  14. History of diabetic gastroparesis (or symptoms suggestive of this disorder, including postprandial bloating or vomiting), malabsorption, inflammatory bowel disease, or any other chronic, clinically important gastrointestinal disorder.
  15. Estimated glomerular filtration rate (eGFR) <65 mL/min/1•73 m2 using the Modification of Diet in Renal Disease Study (MDRD) equation.
  16. Subjects with a history of having or possibly having metallic material in the body or any contraindication for a MR examination.
  17. Screening fasting serum triglycerides ≥600 mg/dL (6•74 mmol/L).
  18. Claustrophobia, or anxiety related to previous negative experiences with magnetic resonance imaging procedures or if the subject is unwilling to participate in magnetic resonance imaging procedures.
  19. Clinically important hematologic disorder (e.g., symptomatic anemia, proliferative bone marrow disorder, thrombocytopenia) at Screening.
  20. History of human immunodeficiency virus (HIV) antibody positive at Screening.
  21. Major surgery (e.g., requiring general anaesthesia) within 12 weeks before Screening, or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study.
  22. Contraindications to the use of dulaglutide (per DULAGLUTIDE US Prescribing Information).
  23. Current use of a corticosteroid medication or immunosuppressive agent, or likely to require treatment with a corticosteroid medication or an immunosuppressive agent.

    Note: Subjects using inhaled, intranasal, intra-articular, or topical corticosteroids, or corticosteroids in therapeutic replacement doses may participate.

  24. Pregnancy or women breastfeeding or planning to become pregnant while enroled in this study.
  25. History of significant cardiac, vascular, pulmonary, renal, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances.
  26. Use of drugs known to cause hepatic steatosis like methotrexate

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 ClinicalTrials.gov identifier (NCT number): NCT03590626


Contacts
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Contact: Surender Rao, MSc 01244141414 ext 6596 yadavsurender89@gmail.com
Contact: Mohammad S Kuchay, MD DM 01244141414 ext 6596 drshafikuchay@gmail.com

Locations
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India
Division Of Endocrinology & Diabetes, Medanta The Medicity Recruiting
Gurgaon, Haryana, India, 122001
Contact: Surender , MSc    01244141414 ext 6596    yadavsurender89@gmail.com   
Contact: Mohammad Shafi Kuchay, MBBS, MD,DM    01244141414 ext 6596    drshafikuchay@gmail.com   
Principal Investigator: Mohammad Shafi Kuchay, MBBS, MD,DM         
Sub-Investigator: Ambrish Mithal, MBBS, MD,DM         
Sponsors and Collaborators
Medanta, The Medicity, India

Publications of Results:

Other Publications:
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Responsible Party: Dr Mohammad Shafi Kuchay, Consultant, Medanta, The Medicity, India
ClinicalTrials.gov Identifier: NCT03590626     History of Changes
Other Study ID Numbers: MMDLIFT01
First Posted: July 18, 2018    Key Record Dates
Last Update Posted: March 11, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Dr Mohammad Shafi Kuchay, Medanta, The Medicity, India:
Non Alcoholic Fatty Liver Disease
Type 2 Diabetes Mellitus
GLP-1 receptor agonist
Dulaglutide
MRI-Proton density fat fraction
Fat Mapping
Non Alcoholic Steatohepatitis

Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Diabetes Mellitus
Diabetes Mellitus, Type 2
Liver Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Digestive System Diseases
Dulaglutide
Immunoglobulin Fc Fragments
Hypoglycemic Agents
Physiological Effects of Drugs
Immunologic Factors