MASLD in Primary Hypothyroidism and Efficacy of Dapaglifozin

Trial statusNot yet recruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18-75
SponsorPost Graduate Institute of Medical Education and Research, Chandigarh

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age 18-75 years

Patients with Primary Overt hypothyroidism (Low FT3/Low FT4 and TSH>ULN)

Disqualifiers

Patients with Diabetes Mellitus(T1DM AND T2DM)

Patient with Secondary Hypothyroidism

Patients with other Endocrinopathies who are at risk of MASLD (T1DM and T2DM, Growth Hormone Insufficiency,Cushing Syndrome)

Patients with concomitant other etiologies for hepatic steatosis or elevated transaminases (chronic viral hepatitis infection, autoimmune hepatitis, Wilson's disease, hemochromatosis, congestive hepatopathy, primary biliary cholangitis, primary sclerosing cholangitis, biliary tract obstruction)

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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

Treatment groups

60 Participants
are divided into 2 treatment groups
Group A: Dapagliflozin Plus levothyroxine GroupExperimental treatment 2 interventions
Group B: Levothyroxine daily and Placebo pill identical to Dapaglifozin for 28 weeksPlacebo comparator 2 interventions

Trial outcomes

Primary outcomes

1

Change in liver fat content

Difference in the change in liver fat content between the two groups at week 28 from the baseline as measured by MRI-PDFF

Time frame
28 weeks

Secondary outcomes

1

Proportion of participants achieving 1 Stage decrease in steatosis at 6 months asassessed by Transient Elastography

Proportion of participants achieving 1 Stage decrease in steatosis at 6 months as assessed by Transient Elastography

Time frame
28 weeks
2

Changes in Improvement in hepatic fibrosis measured by non invasive parameters like Fib4 score at 3 and 6 months

Changes in Improvement in hepatic fibrosis measured by non invasive parameters like Fib4 score at 3 and 6 months

Time frame
28 weeks
3

Changes in Lipid Profile at 3 and 6 months

Changes in Lipid Profile at 3 and 6 months

Time frame
28 weeks

Other outcomes

Locations

1

Map coordinates are unavailable for these locations. Locations are shown below instead.

PGIMER Status unavailable 160012, Chandigarh, PunjabIndiaIndia

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