MASLD in Primary Hypothyroidism and Efficacy of Dapaglifozin

Sponsor
Post Graduate Institute of Medical Education and Research, Chandigarh
Study ID
NCT06373523
Phase
EARLY_PHASE1
Status
Not Yet Recruiting

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Conditions

  • Hepatic Steato-Fibrosis
  • Non-Alcoholic Fatty Liver Disease

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Dapagliflozin 10mg Tab — DRUG
    Dapagliflozin 10mg daily will be given to the treatment arm.Eligible subjects will be followed up until week 28, and will undergo clinical, anthropometric and laboratory assessments (including liver function test and lipid profile) at baseline, week 14 and week 28. They will undergo LSM and CAP By Transient Elastography at baseline, week 14 and week 28, and MRI-PDFF at baseline and week 28. The primary outcome will be a difference in change of liver fat content (measured by MRI-PDFF) at week 28 from baseline between the two groups.
  • Placebo — DRUG
    The placebo pills will be manufactured to be identical in appearance to the study drug(Dapaglifozin 10 mg tablet).
  • Levothyroxine Replacement daily — DRUG
    Levothyroxine Replacement daily for 28 weeka

Study Details

Non-alcoholic fatty liver disease (NAFLD) is a global epidemic with a prevalence of 25-40%.Primary Hypothyroidism is one of Endocrinopathies who are at risk of developing NAFLD/NASH and estimated prevalence of Primary Hypothyroidism in NAFLD patients is 10-15 %.Though First line Management is Dietary changes and lifestyle modifications(LSM),unfortunately Adherence to Lifestyle has been poor,rise of Lean NAFLD is on rise, faster progression of NAFLD,evolving risk factors for NAFLD like endocrinopathies,these push need for Pharmacotherapy.Currently therapies for NAFLD patients without diabetes mellitus (DM) are limited, and are associated with various adverse side effects. Sodium-glucose cotransporter type-2 (SGLT2) inhibitors can reduce hepatic fat content in patients with DM which is independent of glycemic control. However, the role of SGLT2 inhibitors in NAFLD patients without DM has not been investigated.Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) is an emerging non-invasive imaging technique, and is more sensitive than liver biopsy/histology in quantifying liver fat change. Liver stiffness measurement (LSM) by Transient Elastography is a non-invasive method to diagnose fibrosis/cirrhosis with high accuracy.The novelty of utilizing the concept of "drug repositioning" by changing the role of SGLT2 inhibitors in treating DM to treating NAFLD in patients without DM deserves exploration.The investigators propose a double-blind, randomized, placebo-controlled trial to compare the effects of Dapagliflozin (a type of SLGT2 inhibitors) versus placebo (in a 1:1 ratio) in reducing hepatic fat content as measured by MRI-PDFF in NAFLD patients with Primary Hypothyroidism.The study results will determine whether SGLT2 inhibitors can reduce hepatic steatosis/hepatic fibrosis in NAFLD patients with Primary Hypothyroidism.

Key Dates

Start date
Sep 1, 2024
Status verified
Aug 2024
Primary completion
Jun 30, 2025
Completion
Jul 30, 2025

Study Design

Enrollment
60 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Dapagliflozin Plus levothyroxine Group
    Dapagliflozin 10mg daily will be given to the treatment arm in addition to Levothyroxine replacement therapy. Eligible subjects will be followed up until week 28, and will undergo clinical, anthropometric and laboratory assessments (including liver function test and lipid profile) at baseline, week 14 and week 28. They will undergo LSM and CAP By Transient Elastography at baseline, week 14 and week 28, and MRI-PDFF at baseline and week 28. The primary outcome will be a difference in change of liver fat content (measured by MRI-PDFF) at week 28 from baseline between the two groups. The secondary outcomes will be proportion of participants achieving remission of steatosis (MRIPDFF \<5%) at week 28, reduction of liver fibrosis (LSM) and decrease in hepatic steatosis by 1 stage at week 14 and 28 and other secondary outcomes as mentioned above.
  • Placebo Comparator: Levothyroxine daily and Placebo pill identical to Dapaglifozin for 28 weeks
    The placebo pill will be manufactured to identical in appearance to the Dapaglifozin will be given to the Placebo arm in addition to Levothyroxine replacement therapy. Eligible subjects will be followed up until week 28, and will undergo clinical, anthropometric and laboratory assessments (including liver function test and lipid profile) at baseline, week 14 and week 28. They will undergo LSM and CAP By Transient Elastography at baseline, week 14 and week 28, and MRI-PDFF at baseline and week 28. The primary outcome will be a difference in change of liver fat content (measured by MRI-PDFF) at week 28 from baseline between the two groups. The secondary outcomes will be proportion of participants achieving remission of steatosis (MRI PDFF \<5%) at week 28, reduction of liver fibrosis (LSM) and decrease in hepatic steatosis by 1 stage at week 14 and 28 and other secondary outcomes as mentioned above.

Primary Outcome Measure

Change in liver fat content [ Time Frame: 28 weeks ]

Central Contacts

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