A Randomized, Dose-Finding, Proof-of-Concept Study of Berberine Ursodeoxycholate in Patients With Primary Sclerosing Cholangitis
Bibliographic record
Abstract
INTRODUCTION: Primary sclerosing cholangitis (PSC) is a fibroinflammatory disease of the bile ducts leading to cirrhosis and hepatic decompensation. There are no approved pharmaceutical therapies for PSC. Berberine ursodeoxycholate (HTD1801) is an ionic salt of berberine and ursodeoxycholic acid with pleiotropic mechanisms of action. METHODS: An 18-week proof-of-concept study was conducted to assess the safety and efficacy of HTD1801 in PSC. This study had three 6-week periods: (i) a placebo-controlled period, (ii) a treatment extension period, and (iii) a randomized treatment withdrawal period. The primary end point was change from baseline in alkaline phosphatase (ALP) at week 6. RESULTS: Fifty-five patients were randomized and treated; 35 (64%) had inflammatory bowel disease and 22 (40%) had previously received ursodeoxycholic acid. Patients were initially randomized to placebo (n = 16), HTD1801 500 mg BID (n = 15), or HTD1801 1000 mg BID (n = 24). At baseline, mean (range) ALP values were 414 U/L (138-1,048), 397 U/L (237-773), and 335 U/L (122-882) for the placebo, HTD1801 500 mg BID, and HTD1801 1,000 mg BID groups, respectively. At week 6, a significant decrease in ALP was observed with HTD1801 (least square mean; HTD1801 500 mg BID = -53 U/L, P = 0.016; HTD1801 1000 mg BID = -37 U/L, P = 0.019) compared with placebo (98 U/L). ALP reductions were sustained through week 18 in those who remained on therapy, whereas ALP increased in those who crossed over to placebo during period 3. HTD1801 was generally well tolerated; 4 patients experienced serious adverse events, none attributed to HTD1801. DISCUSSION: HTD1801 is associated with significant improvement in ALP and warrants further study as a treatment for PSC.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".