Spironolactone Therapy In Young Women With NASH
Condition: NASH - Nonalcoholic Steatohepatitis
MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Nonalcoholic steatohepatitis (NASH), or fat-related liver inflammation and scarring is
      projected to be the leading cause of cirrhosis in the United States (U.S.) within the next
      few years. Women are at disproportionate risk for NASH, with approximately 15 million U.S.
      women affected. There is an urgent need to understand risk factors for NASH and its
      progression in women, and sex hormones may provide a missing link.

      The investigator's preliminary data support a detrimental role of androgens, or "male sex
      hormones" on fatty liver in women but no studies have evaluated whether androgens are
      associated with liver inflammation and/or scarring from fatty liver (aka NASH). To better
      understand the mechanism by which androgens might promote NASH and/or metabolic co-factors
      that contribute to NASH, the investigators are conducting a pilot clinical trial to primarily
      assess the feasibility of using an androgen blocking medication, spironolactone, in women
      with NASH. Spironolactone was selected because it is has been commonly prescribed for decades
      with good safety profile and tolerability to treat symptoms of high androgens, like acne and
      hirsutism in young women. Though primarily a feasibility-focused study, the investigators
      also aim to explore the pathways by which blocking testosterone receptors might alter the
      biologic processes that promote NASH and its associated metabolic co-morbidities in women.
    

Detailed description: 
      This is a single center, double-blind, placebo-controlled, randomized, (2:1) parallel group
      pilot clinical trial of spironolactone in women with biopsy-proven NASH receiving 6 or 12
      months of spironolactone or placebo. 30 women are targeted for enrollment. Each participant
      will be administered a single dose of spironolactone or placebo once daily for a total of 6
      or 12 months. In person evaluations will take place at Month 1, 3, 6, 9, and 12. There will
      be a telephone follow up visit within 3 months of end of treatment (up to Month 9 or 15).

      This is a pilot clinical trial that is largely feasibility focused. Study outcomes will
      include

        -  Change in liver stiffness on Magnetic Resonance Elastography (MRE)

        -  Change in hepatic steatosis by Magnetic Resonance Proton Density Fat Fraction (PDFF)

        -  Change in visceral adipose tissue (VAT) volume by Magnetic Resonance Imaging (MRI)

        -  Change in NASH histology as assessed by the continuous NAFLD activity score (NAS), which
           measures different components of NASH on liver biopsy.

        -  Biochemical endpoints: serum lipids & HOMA-IR

        -  Feasibility outcomes including Rates (and reasons) for the following: a) % women that
           decline/women contacted for study inclusion (i.e. need for a second liver biopsy,
           concern regarding randomization to placebo) b) % women enrolled/women screened (i.e.
           exclusion criteria too narrow), c) study dropout (i.e. medication side effects, too
           frequent study visits, and/or phlebotomy)
    

Intervention name(s): Spironolactone 100mg; Placebo oral capsule
Intervention type(s): Drug; Drug
Intervention description(s): Spironolactone capsules will be prepared from USP grade powder at a dose of 100 mg.; Matching placebo capsules of the same color, mass, and appearance to the spironolactone capsules will be filled using microcrystalline cellulose powder.
Intervention MeSH terms: Spironolactone
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The following treatment regimens will be used:
Experimental treatment - spironolactone, 100 mg once daily
Placebo or Comparator - one capsule, once daily
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other