A Phase 2 interventional study of N-Acetyl Cysteine (NAC) and Alpha-Lipoic Acid (ALA) in Primary Sclerosing Cholangitis (PSC), sponsored by Brigham and Women's Hospital. Not yet recruiting. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-10-27.
Sponsored by Brigham and Women's Hospital · Phase 2, Interventional, and Other
The goal of this clinical trial is to test whether a type of cell death called disulfidptosis plays a role in primary sclerosing cholangitis (PSC) in adults aged 18 to 70. Researchers will do this by giving participants a study diet and four oral agents designed to block disulfidptosis, then checking whether liver blood tests change. This study is not designed to show that the combination treats PSC.
PSC is a long-term liver disease. In PSC, the bile ducts become inflamed and scarred over time. Bile ducts are small tubes that carry bile from the liver to the gut.
Researchers are testing a new idea about why bile duct cells are damaged in PSC. Cells need a balance of certain sulfur-containing building blocks and the energy to process them. When this balance breaks down, proteins inside the cell can stick together the wrong way. This can cause the cell's inner structure to collapse, and the cell dies. This type of cell death is called disulfidptosis. Researchers think disulfidptosis may contribute to bile duct damage in PSC.
This is a proof-of-principle study. This means it is an early, small study to test whether this idea is correct and worth studying further. Participants will follow a study diet and take four oral agents. Each agent was chosen because it may help protect cells from disulfidptosis:
Alpha-lipoic acid (ALA), a natural antioxidant that helps cells manage stress N-acetylcysteine (NAC), which helps the body make glutathione, a natural antioxidant Nicotinamide riboside (NR), a form of vitamin B3 that helps cells make energy Metformin, a common diabetes medicine that changes how cells use sugar and energy
The main questions it aims to answer are:
There is no comparison group in this study. All participants will receive the study diet and all four agents.
Participants will:
Researchers will watch closely for side effects throughout the study. If liver tests rise too much, researchers will follow set safety steps, which may include stopping one or more study agents. About 15 people will take part.
150 studies on the registry are indexed under Cholangitis, Sclerosing; 38 are open to participants now.
This study's planned enrollment of 15 is below the median of 33 across 97 interventional studies indexed under Cholangitis, Sclerosing.
Browse Cholangitis, Sclerosing studies →Brigham and Women's Hospital is the lead sponsor of 1,265 studies on the registry; 226 are open to participants now.
Of its 116 completed or terminated interventional studies of FDA-regulated products, 65 (56%) have results posted.
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Exclusion Criteria:
Single-arm, open-label. All participants follow a study diet and take four oral agents targeting disulfidptosis for approximately 16 weeks (Baseline through Week 16). Study diet: guided by study dietitians, with grocery support and meal photo logging via the MetaBite app. Study agents: alpha-lipoic acid (ALA) 600 mg once daily in Week 0, then 600 mg twice daily from Week 1; N-acetylcysteine (NAC); nicotinamide riboside (NR) 500 mg twice daily; and metformin extended-release, with doses titrated over the initial weeks per protocol. Enrollment is stratified by inflammatory bowel disease (IBD) status. Study agents may be withdrawn sequentially per the protocol-defined ALP management plan.
Dietary Supplement: N-Acetyl Cysteine (NAC) · Dietary Supplement: Alpha-Lipoic Acid (ALA) · Dietary Supplement: Nicotinamide Riboside (NR) · Drug: Metformin Hydrochloride Extended-Release Tablets · Other: Study Diet
N-acetylcysteine (NAC) capsules (Pure Encapsulations), taken orally. Dose: 1200 mg/day through Week 16. Selected as a precursor of glutathione to support cellular thiol and redox balance as part of a regimen targeting disulfidptosis.
Alpha-lipoic acid (ALA) capsules (Pure Encapsulations), taken orally. Dose: 600 mg once daily in Week 0, then 600 mg twice daily from Week 1 through Week 16. Selected to support cellular antioxidant capacity and redox balance as part of a regimen targeting disulfidptosis.
Nicotinamide riboside (NR) chloride 250 mg capsules (Tru Niagen, ChromaDex), taken orally. Dose: 500 mg twice daily (1,000 mg/day) through Week 16. Selected as an NAD+ precursor to support cellular NADPH availability as part of a regimen targeting disulfidptosis.
Metformin hydrochloride extended-release 500 mg tablets (Granules Pharmaceuticals), taken orally. Dose titrated per protocol to 1000 mg through Week 16. Selected for its effects on cellular glucose and energy metabolism as part of a regimen targeting disulfidptosis.
Participants follow a protocol-specified study diet from Baseline through Week 16, guided by study dietitians. Dietary intake is recorded through meal photographs using the MetaBite for Research app, which dietitians review to provide individualized recommendations. Participants receive grocery support to facilitate adherence.
Change in Serum Alkaline Phosphatase (ALP) From Baseline to Week 16
Serum ALP (U/L) will be measured at Baseline and Week 16. Change will be calculated as the Week 16 value minus the Baseline value. ALP is a marker of cholestatic liver injury commonly elevated in primary sclerosing cholangitis (PSC).
Time frame: Baseline (Week 0) and Week 16
Percentage of Participants With ≥50% Reduction in Serum ALP at Week 16
ALP response is defined as a reduction of 50% or more from baseline at Week 16. Reported as the proportion of participants achieving response, with 95% confidence interval.
Time frame: Baseline (Week 0) and Week 16
Change in Liver Biochemistry From Baseline to Week 16
Change in serum gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin from Baseline to Week 16.
Time frame: Baseline (Week 0) and Week 16
Change in Pro-peptide of Type III Collagen (PRO-C3) From Baseline to Week 16
Serum PRO-C3 (ng/mL), a biomarker of liver fibrogenesis. Change from baseline to Week 16 is reported as absolute and percent change from baseline.
Time frame: Baseline (Week 0) and Week 16
Change in Enhanced Liver Fibrosis (ELF) Score From Baseline to Week 16
The ELF score is a composite serum fibrosis score calculated from hyaluronic acid, amino-terminal propeptide of type III procollagen (PIIINP), and tissue inhibitor of metalloproteinase 1 (TIMP-1). Change from baseline to Week 16 is reported as absolute and percent change from baseline.
Time frame: Baseline (Week 0) and Week 16
Change in LMR Inflammatory Panel Markers From Baseline to Weeks 8 and 16
Serum inflammatory and metabolic markers measured using the LMR Inflammatory Panel. Change from baseline to Week 8 and to Week 16 is reported.
Time frame: Baseline (Week 0), Week 8, and Week 16
No study locations are listed for this record.
Plan to share: Yes
No publications or documents are linked to this record.
Start is estimated for Jan 2027; primary completion for Dec 2028, 23 months later.
Of 23 phase 2 interventional studies under Cholangitis, Sclerosing, half reached primary completion within 37 months of starting (the median), counting those still running; a quarter within 21 and three quarters within 62. This study's planned 23 months is below that.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Acetylcysteine · Thioctic Acid · Nicotinamide-beta-riboside · Metformin
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