Table 3.
Clinical trials and translational research
| Area of concern and specific cholestatic liver disease | Findings | Phase, study description | Clinical trial number | Ref. |
| IL12/IL23 Inflammatory pathway and loss of self-tolerance (Primary biliary cholangitis) | After 28 wk of treatment modest decreases in alkaline phosphatase | Phase 2, open-label proof of concept using Ustekimunab for ursodeoxycholic acid non-responsive patients | NCT01389973 | [72] |
| Ileal bile acid transporter (IBAT) (Primary biliary cholangiti, Alagille syndrome, progressive familial intrahepatic cholestasis) | Bile acid transporter inhibitor A4250 interrupts enterohepatic bile acid circulation at the terminal ileum | Phase 1 (40 individuals) completed Bile acids A4250 either as monotherapy or in combination with colonic release cholestyramine | NCT02963077 | [73] |
| Modified bile acid and FXR agonist derived from chenodeoxycholic acid Obeticholic acid (OCA) (Primary biliary cholangitis) | Durable treatment response; the drug was approved by FDA in May 2017 for non-UDCA responders | Phase 4, double-blind, randomized, placebo-controlled, multicenter (428 patients) estimated completion by 2025 (COBALT study) | NCT02308111 | [34] |
| IBAT inhibition by GSK2330672 | After 14 d, GSK2330672 demonstrated to be safe, well tolerated and reduced pruritus severity | Phase 2 double-blind, randomized, placebo-controlled | NCT01899703 | [74] |
| Bile acids | Significantly reduced ALT and the bile acid intermediate C4 | Phase I: Combination of UDCA and ATRA | NCT01456468 | [75] |
| Bile acids Obeticholic acid monotherapy (Primary biliary cholangitis) | With ursodiol or as monotherapy for 12 mo decreases from baseline in alkaline phosphatase and total bilirubin levels that differed significantly from the placebo. observed changes | Phase 3, double-blind, placebo-controlled trial and long-term safety extension of obeticholic acid (217 patients) (POISE study) | NCT01473524 | [76] |
| Bezafibrate 400 mg alternative | PBC patients with inadequate response to ursodeoxycholic acid alone, treatment with bezafibrate in addition to ursodeoxycholic acid resulted in a rate of complete biochemical response that was significantly higher than the rate with placebo and ursodeoxycholic acid therapy | Phase 3 multi-center, randomized, placebo-controlled, parallel-group (100 patients) (BEZURSO study) | NCT01654731 | [77] |
| Different doses of UDCA in primary sclerosing cholangitis | Significantly reduced ALP values dose-dependently | Phase 2 double-blind, randomized, multi-center, placebo-controlled (159 patients) (NUC3) | NCT01755507 | [78] |
| Pentoxifylline as immunomodulator for primary biliary cholangitis | The study is small, and results were in clinicaltrials.gov, but due to study size no conclusion can be safely achieved | Phase 2, pilot study, open-label Pentoxifylline 400 mg TID for six months (20 participants) | NCT01249092 | Results at clinicaltrials.gov |
| Umbilical cord-derived mesenchymal cells (UC-MSC) | A significant decrease in alkaline phosphatase | Phase1/2 study, randomized, parallel group (100 participants) 12 wk of treatment | NCT01662973 | [79] |
| Mitomycin C in primary sclerosing cholangitis | Final results awaited | Phase 2, double-blind, randomized, parallel group (130 participants) | NCT01688024 | - |
| Curcumin in primary sclerosing cholangitis | Final results awaited | Phase1/2 open-label pilot study Evaluating the safety and efficacy of curcumin (15 participants) | NCT02978339 | - |
| Human monoclonal antibody (BTT1023) that targets the vascular adhesion protein (VAP-1) in primary sclerosing cholangitis | Recruiting | Phase 2, a single arm, two-stage, multicenter, open-label (41 participants) | NCT02239211 | [80] |
| Cenicriviroc a CCR2/CCR5 inhibitor proof of concept in primary sclerosing cholangitis | Results awaited | Phase 2, proof of concept, open-label (24 participants) (PERSEUS study) | NCT02653625 | - |
| Bile acids Maralixibat Apical bile acids transporter inhibition (ASBTi) in primary sclerosing cholangitis | Although results are online, complete information is still awaited | Phase 2, pilot, open-label | NCT02061540 | Results available at clinicaltrial.gov |
| Immunomodulation Simtuzumab in primary sclerosing cholangitis Monoclonal antibody against lysyl oxidase-like 2 (LOXL2) | Results awaited | Phase 2b, dose-ranging, randomized, double-blind, placebo-controlled (235 participants) | NCT01672853 | - |
| Bile acids Obethicolic acid in primary biliary cholangitis | Treatment with OCA 5-10 mg reduced serum ALP in patients with PSC. Mild to moderate dose-related pruritus was the most common adverse event | Phase 2, double-blind, placebo-controlled trial. Dose-Finding (AESOP) | NCT02177136 | [80] |
PSC: Primary sclerosing cholangitis.