Effect on Non-Alcoholic Fatty Liver Disease in Patients With Type 2 Diabetes Mellitus With Gastric Inhibitory Polypeptide/Glucagon Like Peptide-1 Analogue

NCT05751720 | Unknown Phase 1

• 1 other identifier: UAEU_CMHS_IM_startup_AA01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Obesity and type 2 Diabetes Mellitus prevalence has doubled in the last 30 years and nearly one fifth of UAE population has Type 2 Diabetes while more than quarter has obesity. Non-alcoholic fatty liver disease is present in more than 30% of patients with type 2 diabetes and in \> 50% patient with obesity 20% of patients with Non-alcoholic fatty liver disease progress to develop non-alcoholic steatohepatitis which can lead to liver failure and hepatocellular carcinoma. This study aims to use GLP-1 analogue to see effects on liver fat deposition after six months of treatment There is no current randomised study on treatment of non-alcoholic steatohepatitis in United Arab Emirates population; so once completed this will the first study. This study will pave the way for developing a treatment pathway for patients with non-alcoholic fatty liver disease.

Conditions

Non-Alcoholic Fatty Liver Disease; Non-alcoholic Steatohepatitis; Type 2 Diabetes; Liver Fat

Outcome Measures

Primary Outcomes (2)

• change in liver stiffness in terms of kPa

  To measure the liver stiffness pre and post GLP-1 analogue/GIP treatment for 6 months to assess any change in liver stiffness in terms of kPa in patient with type 2 Diabetes Mellitus and NAFLD

  12 months

• Change in Liver fat quantification

  To measure the liver fat quantification via MRI proton density fraction, pre and post GLP-1 analogue/GIP treatment for 6 months to assess any change in total liver fat content in patients with type 2 Diabetes Mellitus and NAFLD

  12 months

Secondary Outcomes (2)

• change in BMI

  12 months

• Glycaemic control

  12 months

Study Arms (1)

GLP-1/GIP Arm pre and post intervention

EXPERIMENTAL

The adult patients with type 2 diabetes mellitus attending Tawam Hospital Diabetes clinic, who are identified as having fatty liver disease either via ultrasound or biochemical parameter of NFS. We will aim to include minimum 30 patients fulfilling the selection criteria as below. Informed written consent will be obtained . Intervention group will receive GLP-1 analogues (subcutaneous Tirzepatide or oral semaglutide). The blood tests will be done at baseline, 3 months of treatment and at 6 months of treatment. Liver imaging (fibroscan and/or MRI fat measurement) will be done at baseline and at 6 months to see if there is any change.The KPa improvement in liver stiffness and total fat estimation pre and post intervention in both groups will assessed

Drug: GIP/GLP-1a

Interventions

GIP/GLP-1a DRUG

The group will receive GLP-1 analogues (subcutaneous Tirzepatide). The dose of Tirzepatide is 0.25 mg once weekly for 4 weeks then 0.5 mg once weekly.

GLP-1/GIP Arm pre and post intervention

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18; either male or female
• Diagnosed to have Type 2 Diabetes Mellitus for \> 1 year.
• Presence of NAFLD advanced fibrosis (F3 and F4; defined by NFS of \> 0.676)
• Able to consent independently
• Not already on GLP-1 analogues or SGLT2 inhibitors or pioglitazone
• Good general health
• BMI\> 19 but less than 40

You may not qualify if:

• Known history of alcohol excess or current alcohol use of \> 20 g/week
• Evidence of pre-existing liver or biliary disease (hepatoma, biliary tract obstruction; liver cirrhosis secondary to viral infection or immune/ congenital).
• Known or suspected hypersensitivity to GLP-1 analogues or pioglitazone.
• Receipt of any investigational medicinal product within 30 days before screening.
• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using highly effective contraceptive methods.
• Endocrinopathies (e.g., Cushing syndrome)
• Personal history of heart disease especially heart failure
• History of malignant neoplasm within 5 years prior to the day of screening. Basal and squamous cell skin cancer and any carcinoma in-situ is allowed.
• eGFR \< 30
• history of heamturia or bladder cancer
• history of osteoporosis
• ALT ≥3.5 times the upper normal limit (UNL)
• Taking steroids, antipsychotics or progesterone preparations
• Uncontrolled hypertension
• Positive insulinoma associated-protein 2 (IA-2) antibodies or anti-glutamic acid decarboxylase (anti-GAD) antibodies.

Sponsors & Collaborators

• Dr Adnan Agha: lead

Study Sites (1)

Internal Medicine, College of Medicine and Health Sciences

Al Ain City, Abu Dhabi Emirate, 15551, United Arab Emirates

RECRUITING

Related Publications (2)

• Imajo K, Kessoku T, Honda Y, Tomeno W, Ogawa Y, Mawatari H, Fujita K, Yoneda M, Taguri M, Hyogo H, Sumida Y, Ono M, Eguchi Y, Inoue T, Yamanaka T, Wada K, Saito S, Nakajima A. Magnetic Resonance Imaging More Accurately Classifies Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease Than Transient Elastography. Gastroenterology. 2016 Mar;150(3):626-637.e7. doi: 10.1053/j.gastro.2015.11.048. Epub 2015 Dec 8.

  PMID: 26677985 BACKGROUND

• Kaswala DH, Lai M, Afdhal NH. Fibrosis Assessment in Nonalcoholic Fatty Liver Disease (NAFLD) in 2016. Dig Dis Sci. 2016 May;61(5):1356-64. doi: 10.1007/s10620-016-4079-4. Epub 2016 Mar 26.

  PMID: 27017224 BACKGROUND

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2; Fatty Liver

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Adnan Agha, FRCP

  United Arab Emirates University, College of Medicine & Health Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Adnan Agha, FRCP

CONTACT

+971-3-7673333; adnanagha@uaeu.ac.ae

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor, Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University

Model Details: Intervention group will receive GLP-1 analogues (subcutaneous Tirzepatide or oral semaglutide).The dose of oral semaglutide will be 3 mg daily for 30 days (initiation) and if dose then increased to 7 mg daily for 6 months while the dose of Tirzepatide is 0.25 mg once weekly for 4 weeks then 0.5 mg once weekly. The blood tests will be done at baseline, 3 months of treatment and at 6 months of treatment. Liver imaging (fibroscan and/or MRI fat measurement) will be done at baseline and at 6 months to see if there is any change.

Study Record Dates

• First Submitted: February 13, 2023
• First Posted: March 2, 2023
• Study Start: October 1, 2023
• Primary Completion: October 1, 2024
• Study Completion: February 1, 2025
• Last Updated: January 12, 2024

Record last verified: 2024-01

Locations

AE (1)