Androgens and NAFLD Longitudinal Cohort Study

NCT ID: NCT06124261

Last Updated: 2025-03-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

150 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-01-22

Study Completion Date

2028-12-31

Brief Summary

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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

Detailed Description

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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.

Conditions

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PCOS NAFLD NASH

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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MASLD and PCOS hyperandrogenism

Patients with MASLD and PCOS with the phenotype of hyperandrogenism

No interventions assigned to this group

MASLD and PCOS non-hyperandrogenism

Patients with MASLD and PCOS with the phenotype of non-hyperandrogenism

No interventions assigned to this group

MASLD and no-PCOS

Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and no PCOS

No interventions assigned to this group

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

42 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Duke University

OTHER

Sponsor Role collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Monika A Sarkar, M.D., M.A.S

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Ayako Suzuki, M.D.,Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

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University of California San Francisco

San Francisco, California, United States

Site Status RECRUITING

Duke University

Durham, North Carolina, United States

Site Status NOT_YET_RECRUITING

Countries

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United States

Central Contacts

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Elle K Oberweis-Manion, B.A.

Role: CONTACT

415-502-3725

Facility Contacts

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Elle K Oberweis-Manion, B.A.

Role: primary

415-502-3725

Jasmine Gamez, B.S.

Role: backup

415-353-9240

Linda Perry, R.N.

Role: primary

References

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Sarkar M, Terrault N, Chan W, Cedars MI, Huddleston HG, Duwaerts CC, Balitzer D, Gill RM. Polycystic ovary syndrome (PCOS) is associated with NASH severity and advanced fibrosis. Liver Int. 2020 Feb;40(2):355-359. doi: 10.1111/liv.14279. Epub 2019 Nov 12.

Reference Type BACKGROUND
PMID: 31627243 (View on PubMed)

Sarkar MA, Suzuki A, Abdelmalek MF, Yates KP, Wilson LA, Bass NM, Gill R, Cedars M, Terrault N; NASH Clinical Research Network. Testosterone is Associated With Nonalcoholic Steatohepatitis and Fibrosis in Premenopausal Women With NAFLD. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1267-1274.e1. doi: 10.1016/j.cgh.2020.09.045. Epub 2020 Oct 1.

Reference Type BACKGROUND
PMID: 33010412 (View on PubMed)

Sarkar M, Yates K, Suzuki A, Lavine J, Gill R, Ziegler T, Terrault N, Dhindsa S. Low Testosterone Is Associated With Nonalcoholic Steatohepatitis and Fibrosis Severity in Men. Clin Gastroenterol Hepatol. 2021 Feb;19(2):400-402.e2. doi: 10.1016/j.cgh.2019.11.053. Epub 2019 Dec 5.

Reference Type BACKGROUND
PMID: 31812658 (View on PubMed)

Sarkar M, Terrault N, Duwaerts CC, Tien P, Cedars MI, Huddleston H. The Association of Hispanic Ethnicity with Nonalcoholic Fatty Liver Disease in Polycystic Ovary Syndrome. Curr Opin Gynecol Obstet. 2018 Feb 20;1(1):24-33. Epub 2018 Apr 5.

Reference Type BACKGROUND
PMID: 30112518 (View on PubMed)

Other Identifiers

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1R01DK134633-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

23-39040

Identifier Type: -

Identifier Source: org_study_id

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