Effect of Dulaglutide on Liver Fat in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease

• Status: Completed
• Trial end date: 2020-02-18
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Medanta, The Medicity, India
• Treatments: Dulaglutide; Immunoglobulin Fc Fragments

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