Trial Outcomes & Findings for Spironolactone Therapy In Young Women With NASH (NCT NCT03576755)

NCT ID: NCT03576755

Last Updated: 2025-03-26

Results Overview

The investigators will assess for change in the MRE quantified liver stiffness in kilopascals (kPA)

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

20 participants

Primary outcome timeframe

6 or 12 Months

Results posted on

2025-03-26

Participant Flow

Three patients withdrew consent prior to randomization. All other participants were immediately randomized once baseline was completed.

Participant milestones

Participant milestones
Measure	Spironolactone 6 spironolactone, 100 mg capsule administered orally once daily for 6 months Spironolactone 100mg: Spironolactone capsules will be prepared from USP grade powder at a dose of 100 mg.	Placebo 6 matching placebo capsule administered orally once daily for 6 months Placebo oral capsule: Matching placebo capsules of the same color, mass, and appearance to the spironolactone capsules will be filled using microcrystalline cellulose powder.	Spironolactone 12 spironolactone, 100 mg capsule administered orally once daily for 12 months Spironolactone 100mg: Spironolactone capsules will be prepared from USP grade powder at a dose of 100 mg.	Placebo 12 matching placebo capsule administered orally once daily for 12 months Placebo oral capsule: Matching placebo capsules of the same color, mass, and appearance to the spironolactone capsules will be filled using microcrystalline cellulose powder.
Overall Study STARTED	3	4	8	2
Overall Study COMPLETED	2	4	8	2
Overall Study NOT COMPLETED	1	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Spironolactone 6 spironolactone, 100 mg capsule administered orally once daily for 6 months Spironolactone 100mg: Spironolactone capsules will be prepared from USP grade powder at a dose of 100 mg.	Placebo 6 matching placebo capsule administered orally once daily for 6 months Placebo oral capsule: Matching placebo capsules of the same color, mass, and appearance to the spironolactone capsules will be filled using microcrystalline cellulose powder.	Spironolactone 12 spironolactone, 100 mg capsule administered orally once daily for 12 months Spironolactone 100mg: Spironolactone capsules will be prepared from USP grade powder at a dose of 100 mg.	Placebo 12 matching placebo capsule administered orally once daily for 12 months Placebo oral capsule: Matching placebo capsules of the same color, mass, and appearance to the spironolactone capsules will be filled using microcrystalline cellulose powder.
Overall Study Withdrawal by Subject	1	0	0	0

Baseline Characteristics

Spironolactone Therapy In Young Women With NASH

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Spironolactone n=11 Participants spironolactone, 100 mg capsule administered orally once daily for 6 or 12 months Spironolactone 100mg: Spironolactone capsules will be prepared from USP grade powder at a dose of 100 mg.	Placebo n=6 Participants matching placebo capsule administered orally once daily for 6 or 12 months Placebo oral capsule: Matching placebo capsules of the same color, mass, and appearance to the spironolactone capsules will be filled using microcrystalline cellulose powder.	Total n=17 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=99 Participants	6 Participants n=107 Participants	17 Participants n=206 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Continuous	33 Years n=99 Participants	30 Years n=107 Participants	32 Years n=206 Participants
Sex: Female, Male Female	11 Participants n=99 Participants	6 Participants n=107 Participants	17 Participants n=206 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=99 Participants	4 Participants n=107 Participants	8 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=99 Participants	2 Participants n=107 Participants	9 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) White	9 Participants n=99 Participants	5 Participants n=107 Participants	14 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United States	11 Participants n=99 Participants	6 Participants n=107 Participants	17 Participants n=206 Participants
Diagnosed with PCOS	6 Participants n=99 Participants	2 Participants n=107 Participants	8 Participants n=206 Participants

PRIMARY outcome

Timeframe: 6 or 12 Months

Population: Median (IQR) change in kPA will be reported from baseline to 6 months and separately baseline to 12 months by treatment group.

The investigators will assess for change in the MRE quantified liver stiffness in kilopascals (kPA)

Outcome measures

Outcome measures
Measure	Spironolactone 6 n=10 Participants spironolactone, 100 mg capsule administered orally once daily for 6 Spironolactone 100mg: Spironolactone capsules will be prepared from USP grade powder at a dose of 100 mg.	Placebo 6 n=6 Participants matching placebo capsule administered orally once daily for 6 Placebo oral capsule: Matching placebo capsules of the same color, mass, and appearance to the spironolactone capsules will be filled using microcrystalline cellulose powder.	Sprionolactone 12 n=8 Participants spironolactone, 100 mg capsule administered orally once daily for 12 Spironolactone 100mg: Spironolactone capsules will be prepared from USP grade powder at a dose of 100 mg.	Placebo 12 n=3 Participants matching placebo capsule administered orally once daily for 12 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)	0.025 Change in kPA Interval -0.33 to 0.35	-0.265 Change in kPA Interval -0.34 to 0.09	0.105 Change in kPA Interval -0.035 to 0.77	0.135 Change in kPA Interval -0.22 to 0.49

SECONDARY outcome

Timeframe: 6 or 12 months

Population: Standard error change in % will be reported from baseline to 6 months and separately baseline to 12 months by treatment group.

The investigators will assess for % change in fat fraction by MRI-PDFF

Outcome measures

Outcome measures
Measure	Spironolactone 6 n=10 Participants spironolactone, 100 mg capsule administered orally once daily for 6 Spironolactone 100mg: Spironolactone capsules will be prepared from USP grade powder at a dose of 100 mg.	Placebo 6 n=6 Participants matching placebo capsule administered orally once daily for 6 Placebo oral capsule: Matching placebo capsules of the same color, mass, and appearance to the spironolactone capsules will be filled using microcrystalline cellulose powder.	Sprionolactone 12 n=8 Participants spironolactone, 100 mg capsule administered orally once daily for 12 Spironolactone 100mg: Spironolactone capsules will be prepared from USP grade powder at a dose of 100 mg.	Placebo 12 n=3 Participants matching placebo capsule administered orally once daily for 12 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 Hepatic Steatosis by Magnetic Resonance Proton Density Fat Fraction (PDFF)	-4.95 % change Interval -6.6 to 3.1	-3.05 % change Interval -6.6 to 11.1	-5.20 % change Interval -6.35 to -2.95	-3.20 % change Interval -8.3 to 0.2

SECONDARY outcome

Timeframe: 6 or 12 months

Population: Median (IQR) change in cm\^2 will be reported from baseline to 6 months and separately baseline to 12 months by treatment group.

The investigators will assess for change in the MRI quantified VAT volume cm\^2

Outcome measures

Outcome measures
Measure	Spironolactone 6 n=10 Participants spironolactone, 100 mg capsule administered orally once daily for 6 Spironolactone 100mg: Spironolactone capsules will be prepared from USP grade powder at a dose of 100 mg.	Placebo 6 n=6 Participants matching placebo capsule administered orally once daily for 6 Placebo oral capsule: Matching placebo capsules of the same color, mass, and appearance to the spironolactone capsules will be filled using microcrystalline cellulose powder.	Sprionolactone 12 n=8 Participants spironolactone, 100 mg capsule administered orally once daily for 12 Spironolactone 100mg: Spironolactone capsules will be prepared from USP grade powder at a dose of 100 mg.	Placebo 12 n=3 Participants matching placebo capsule administered orally once daily for 12 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 Visceral Adipose Tissue (VAT) Volume by Magnetic Resonance Imaging (MRI)	3.3 cm^2 Interval -4.4 to 9.6	11.9 cm^2 Interval -5.2 to 12.9	6.8 cm^2 Interval -7.4 to 16.8	18.3 cm^2 Interval 10.0 to 32.6

SECONDARY outcome

Timeframe: 6 or 12 Months

Population: Median (IQR) change will be reported (mU/L\*mmol/L) from baseline to 6 months and separately from baseline to 12 months by treatment group.

The investigators will assess change in continuous measures of HOMA-IR as insulin resistance is known to contribute to NASH progression. HOMA-IR was calculated as: Fasting serum insulin (mU/L) x Fasting plasma glucose (mmol/L) / 22.5. Higher scores indicate greater insulin resistance and a worse outcome. There is no theoretical minimum and/or maximum value for HOMA-IR.

Outcome measures

Outcome measures
Measure	Spironolactone 6 n=10 Participants spironolactone, 100 mg capsule administered orally once daily for 6 Spironolactone 100mg: Spironolactone capsules will be prepared from USP grade powder at a dose of 100 mg.	Placebo 6 n=6 Participants matching placebo capsule administered orally once daily for 6 Placebo oral capsule: Matching placebo capsules of the same color, mass, and appearance to the spironolactone capsules will be filled using microcrystalline cellulose powder.	Sprionolactone 12 n=8 Participants spironolactone, 100 mg capsule administered orally once daily for 12 Spironolactone 100mg: Spironolactone capsules will be prepared from USP grade powder at a dose of 100 mg.	Placebo 12 n=3 Participants matching placebo capsule administered orally once daily for 12 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 HOMA-IR (Homeostatic Model Assessment (HOMA) for Insulin Resistance (IR)).	5.29 mU/L*mmol/L Interval 3.46 to 14.3	4.49 mU/L*mmol/L Interval 3.63 to 7.8	5.99 mU/L*mmol/L Interval 3.43 to 7.3	11.90 mU/L*mmol/L Interval 4.8 to 24.62

SECONDARY outcome

Timeframe: 6 or 12 Months

Population: Median (IQR) change will be reported from baseline to 12 months by treatment group.

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). The NAS scoring is used to assess the severity and activity of NAFLD taking into account three components: steatosis (fat accumulation) scored from 0 to 3, Lobular inflammation scored from 0 to 3, and hepatocyte ballooning scored from 0 to 2. The total NAS score ranges from 0 to 8. Higher scores indicate greater disease activity. Interpretation of NAS scores: 0-2 no significant NAFLD, 3-4, borderline NASH, and 5-8, definite NASH. As this was an optional component of the study, none of the participants who completed 6 months chose to undergo the biopsy which is why we only have 12 month measurements.

Outcome measures

Outcome measures
Measure	Spironolactone 6 n=3 Participants spironolactone, 100 mg capsule administered orally once daily for 6 Spironolactone 100mg: Spironolactone capsules will be prepared from USP grade powder at a dose of 100 mg.	Placebo 6 n=2 Participants matching placebo capsule administered orally once daily for 6 Placebo oral capsule: Matching placebo capsules of the same color, mass, and appearance to the spironolactone capsules will be filled using microcrystalline cellulose powder.	Sprionolactone 12 spironolactone, 100 mg capsule administered orally once daily for 12 Spironolactone 100mg: Spironolactone capsules will be prepared from USP grade powder at a dose of 100 mg.	Placebo 12 matching placebo capsule administered orally once daily for 12 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 the Non-Alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS 0-8).	2 scores on a scale Interval 0.0 to 2.0	2.5 scores on a scale Interval 2.0 to 3.0	—	—

Adverse Events

Spironolactone

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Principal Investigator: Dr. Monika Sarkar

University of California San Francisco

Phone: 415-502-2656

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Spironolactone n=11 participants at risk spironolactone, 100 mg capsule administered orally once daily for 6 or 12 months Spironolactone 100mg: Spironolactone capsules will be prepared from USP grade powder at a dose of 100 mg.	Placebo n=6 participants at risk matching placebo capsule administered orally once daily for 6 or 12 months Placebo oral capsule: Matching placebo capsules of the same color, mass, and appearance to the spironolactone capsules will be filled using microcrystalline cellulose powder.
General disorders Polydipsia	9.1% 1/11 • Number of events 1 • Through study completion on average 1 year.	16.7% 1/6 • Number of events 1 • Through study completion on average 1 year.
Musculoskeletal and connective tissue disorders Muscle Cramping	9.1% 1/11 • Number of events 2 • Through study completion on average 1 year.	0.00% 0/6 • Through study completion on average 1 year.
Renal and urinary disorders Dark urine	9.1% 1/11 • Number of events 1 • Through study completion on average 1 year.	0.00% 0/6 • Through study completion on average 1 year.
Musculoskeletal and connective tissue disorders Right ankle pain	9.1% 1/11 • Number of events 1 • Through study completion on average 1 year.	0.00% 0/6 • Through study completion on average 1 year.
Musculoskeletal and connective tissue disorders Neck stiffness/pain	18.2% 2/11 • Number of events 2 • Through study completion on average 1 year.	0.00% 0/6 • Through study completion on average 1 year.
Gastrointestinal disorders Vomiting	9.1% 1/11 • Number of events 2 • Through study completion on average 1 year.	33.3% 2/6 • Number of events 2 • Through study completion on average 1 year.
Reproductive system and breast disorders Vaginal bleeding	9.1% 1/11 • Number of events 1 • Through study completion on average 1 year.	0.00% 0/6 • Through study completion on average 1 year.
Musculoskeletal and connective tissue disorders Lower back pain	18.2% 2/11 • Number of events 2 • Through study completion on average 1 year.	0.00% 0/6 • Through study completion on average 1 year.
Respiratory, thoracic and mediastinal disorders Cough and sore throat	18.2% 2/11 • Number of events 2 • Through study completion on average 1 year.	16.7% 1/6 • Number of events 1 • Through study completion on average 1 year.
Gastrointestinal disorders Stomach cramping/abdominal pain	18.2% 2/11 • Number of events 2 • Through study completion on average 1 year.	50.0% 3/6 • Number of events 3 • Through study completion on average 1 year.
General disorders Lightheadeness	0.00% 0/11 • Through study completion on average 1 year.	16.7% 1/6 • Number of events 1 • Through study completion on average 1 year.
General disorders Fatigue/ increased fatigue	9.1% 1/11 • Number of events 1 • Through study completion on average 1 year.	50.0% 3/6 • Number of events 3 • Through study completion on average 1 year.
Immune system disorders Fever	0.00% 0/11 • Through study completion on average 1 year.	33.3% 2/6 • Number of events 3 • Through study completion on average 1 year.
Ear and labyrinth disorders Worsened bilateral otalgia/otitis externa	0.00% 0/11 • Through study completion on average 1 year.	16.7% 1/6 • Number of events 1 • Through study completion on average 1 year.
Immune system disorders nasal congestion, sneezing, and rhinorrhea	9.1% 1/11 • Number of events 1 • Through study completion on average 1 year.	16.7% 1/6 • Number of events 1 • Through study completion on average 1 year.
Psychiatric disorders Increased anxiety/depression	0.00% 0/11 • Through study completion on average 1 year.	16.7% 1/6 • Number of events 1 • Through study completion on average 1 year.
Musculoskeletal and connective tissue disorders trigger finger of right hand	0.00% 0/11 • Through study completion on average 1 year.	16.7% 1/6 • Number of events 1 • Through study completion on average 1 year.
Gastrointestinal disorders Nausea	9.1% 1/11 • Number of events 1 • Through study completion on average 1 year.	33.3% 2/6 • Number of events 2 • Through study completion on average 1 year.
Renal and urinary disorders Increased urination	18.2% 2/11 • Number of events 2 • Through study completion on average 1 year.	16.7% 1/6 • Number of events 1 • Through study completion on average 1 year.
Eye disorders eye twitching	9.1% 1/11 • Number of events 1 • Through study completion on average 1 year.	0.00% 0/6 • Through study completion on average 1 year.
Gastrointestinal disorders Diarrhea	9.1% 1/11 • Number of events 1 • Through study completion on average 1 year.	16.7% 1/6 • Number of events 1 • Through study completion on average 1 year.
Infections and infestations Herpes	0.00% 0/11 • Through study completion on average 1 year.	16.7% 1/6 • Number of events 1 • Through study completion on average 1 year.
General disorders Insomnia	9.1% 1/11 • Number of events 1 • Through study completion on average 1 year.	0.00% 0/6 • Through study completion on average 1 year.
General disorders bilateral hand itchiness	9.1% 1/11 • Number of events 1 • Through study completion on average 1 year.	0.00% 0/6 • Through study completion on average 1 year.
Surgical and medical procedures shoulder and abdominal pain after biopsy	9.1% 1/11 • Number of events 1 • Through study completion on average 1 year.	0.00% 0/6 • Through study completion on average 1 year.
Reproductive system and breast disorders amenorrhea	9.1% 1/11 • Number of events 1 • Through study completion on average 1 year.	0.00% 0/6 • Through study completion on average 1 year.
Infections and infestations COVID-19 infection	0.00% 0/11 • Through study completion on average 1 year.	16.7% 1/6 • Number of events 1 • Through study completion on average 1 year.
General disorders Increased hair loss	0.00% 0/11 • Through study completion on average 1 year.	16.7% 1/6 • Number of events 1 • Through study completion on average 1 year.
General disorders Headache	0.00% 0/11 • Through study completion on average 1 year.	16.7% 1/6 • Number of events 1 • Through study completion on average 1 year.
Musculoskeletal and connective tissue disorders left pinched nerve and neck pain	0.00% 0/11 • Through study completion on average 1 year.	16.7% 1/6 • Number of events 1 • Through study completion on average 1 year.