Androgens and NAFLD Longitudinal Cohort Study

University of California San Francisco (UCSF) logo

University of California San Francisco (UCSF)

Status

Enrolling

Conditions

NASH
PCOS
NAFLD

Study type

Observational

Funder types

Other
NIH

Identifiers

NCT06124261
1R01DK134633-01A1 (Other Grant/Funding Number)
23-39040

Details and patient eligibility

About

The researchers want to learn how androgens, a type of sex hormone, might affect nonalcoholic fatty liver (NAFLD) in young women over time. NAFLD happens when fat builds up in the liver which can cause damage to the liver such as inflammation or scarring. Young women with a condition called polycystic ovary syndrome (PCOS) have a high risk for NAFLD, and they often have high androgen levels too. So the researchers are recruiting young women with PCOS as well as those without PCOS, and will compare changes in NAFLD over time between young women with and without PCOS. This study is funded by the National Institutes of Health

Full description

The studies central hypothesis is that androgens promote liver injury and NAFLD/NASH progression in PCOS, which occurs through aberrant lipid activity (including lipotoxicity and dysregulated de novo lipogenesis), in part from androgenic effects on visceral adipose tissue (VAT). Data in young women taking exogenous testosterone show redistribution of fat from subcutaneous to visceral stores In the general population, VAT promotes NASH through several established pathways, including production of tissue injurious or "lipotoxic" lipids such as some phospholipid, sphingomyelin, and ceramide species. Recent data show androgen- associated increase in serum glycerophospholipids in women with PCOS, a lipid class that is associated with NASH in women. Additionally, androgen-associated de novo lipogenesis (DNL) may contribute to NASH in women. Hepatic DNL is a key source of lipid accumulation, and co-investigators at Duke University recently discovered an enzymatic balance that regulates hepatic DNL with dysregulation of this pathway (reflected by branched-chain keto and amino acids) predictive of prevalent NASH in humans. Androgen-induced de novo lipogenesis also occurs in cultured hepatocytes from women (but not men) supporting the researchers focused evaluation of the relationship between androgens, dysregulated hepatic DNL, and NASH in PCOS. As existing data support androgenic effects on hepatic and visceral fat in women, the researchers will now determine the relationship of androgens with liver injury and progression in PCOS and the potential mechanistic contributions of VAT and aberrant lipid metabolism to this process. The team includes clinical and translational researchers at two centers (UCSF and Duke) with expertise in NAFLD, PCOS, obesity, and lipid metabolism, with a track record of collaboration. The study team will leverage an existing well-characterized PCOS cohort29 to follow 150 reproductive-aged women with NASH (125 PCOS and 25 non-PCOS controls) to accomplish this.

Enrollment

150 estimated patients

Sex

Female

Ages

18 to 40 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Metabolic associated steatohepatitis (MASH) (formerly NASH)
  • PCOS
  • Non-PCOS

Exclusion criteria

  • High levels of alcohol use (more than 7 drinks a week)
  • Current pregnancy
  • Other causes of hepatic steatosis
  • Weight loss of more than 10% body weight in the last 6 months

Trial design

150 participants in 3 patient groups

MASLD and PCOS hyperandrogenism
Description:
Patients with MASLD and PCOS with the phenotype of hyperandrogenism
MASLD and PCOS non-hyperandrogenism
Description:
Patients with MASLD and PCOS with the phenotype of non-hyperandrogenism
MASLD and no-PCOS
Description:
Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and no PCOS

Trial contacts and locations

2

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Central trial contact

Elle K Oberweis-Manion, B.A.

Data sourced from clinicaltrials.gov

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