Spironolactone Therapy In Young Women With NASH
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|ClinicalTrials.gov Identifier: NCT03576755|
Recruitment Status : Recruiting
First Posted : July 3, 2018
Last Update Posted : August 6, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|NASH - Nonalcoholic Steatohepatitis||Drug: Spironolactone 100mg Drug: Placebo oral capsule||Phase 1 Phase 2|
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 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 12 months. In person evaluations will take place at Month 1, 3, 6, 9, 12, and at the follow up visit within 3 months of end of treatment (up to Month 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)
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||
The following treatment regimens will be used:
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
Due to the objectives of the study, the identity of test and control treatments will not be known to investigators, research staff, or patients. The following study procedures will be in place to ensure double-blind administration of study treatments Access to the randomization code will be strictly controlled. A color and size-matched placebo capsule that looks identical to the spironolactone capsule will be used.
Packaging and labeling of test and control treatments will be identical to maintain the blind.
The study blind will be broken on completion of the clinical study, after all study endpoints have been ascertained by blinded study coordinators and after the study database has been locked.
During the study, the blind may be broken only in emergencies when knowledge of the patient's treatment group is necessary for further patient management. The UCSF investigational pharmacy would then be notified and responsible for unblinding.
|Official Title:||Pilot Randomized Controlled Trial of Spironolactone in Young Women With Nonalcoholic Steatohepatitis (NASH)|
|Actual Study Start Date :||January 9, 2019|
|Estimated Primary Completion Date :||July 2022|
|Estimated Study Completion Date :||July 2022|
spironolactone, 100 mg capsule administered orally once daily for 12 months
Drug: Spironolactone 100mg
Spironolactone capsules will be prepared from USP grade powder at a dose of 100 mg.
Placebo Comparator: placebo
matching placebo capsule administered orally once daily for 12 months
Drug: Placebo oral capsule
Matching placebo capsules of the same color, mass, and appearance to the spironolactone capsules will be filled using microcrystalline cellulose powder.
- Change in liver stiffness on Magnetic Resonance Elastography (MRE) [ Time Frame: 12 Months ]The investigators will assess for change in the MRE quantified liver stiffness in kilopascals (kPA)
- Change in hepatic steatosis by Magnetic Resonance Proton Density Fat Fraction (PDFF) [ Time Frame: 12 months ]The investigators will assess for % change in fat fraction by MRI-PDFF
- Change in visceral adipose tissue (VAT) volume by Magnetic Resonance Imaging (MRI) [ Time Frame: 12 months ]The investigators will assess for % change in VAT as quantified by MRI
- Change HOMA-IR (Homeostatic model assessment (HOMA) for insulin resistance (IR)). [ Time Frame: 12 Months ]The investigators will assess change in continuous measures of HOMA-IR as insulin resistance is known to contribute to NASH progression.
- Change in the NAFLD activity score (NAS 0-8). [ Time Frame: 12 Months ]The investigators will assess for change in this histologic scoring system of NASH as a continuous measure among women willing to undergo end of treatment biopsy (not required).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03576755
|Contact: Monika A Sarkar, MD, MAS||(415) firstname.lastname@example.org|
|Contact: Norah Terrault, MD, MPH||(415) 353-2318||Norah.email@example.com|
|United States, California|
|University of California San Francisco||Recruiting|
|San Francisco, California, United States, 94143|
|Contact: Monika A Sarkar, MD 415-502-2656 firstname.lastname@example.org|