Research
Division of Gastroenterology & Hepatology
RESEARCH
The UVA Division of Gastroenterology & Hepatology has a rich tradition of clinical, translational and basic research that has had a major impact on human health, and that helps differentiate its care from other health systems in the region and state. For example, breakthrough studies performed in the division led to the identification of Helicobacter pylori as a major cause of peptic ulcer disease, gastric carcinomas and mucosa-associated lymphoid tissue lymphomas. The Nobel Prize in Medicine was awarded to Barry Marshall, MD, a former faculty member of the Division of Gastroenterology, for his discovery of H. pylori, in work that was performed while he was on faculty in the division.
Other recent scientific discoveries by investigators in the division have produced promising new potential drug targets for modulating intestinal inflammation and microbiota in inflammatory bowel diseases and led to new insights into enteric infections, the immunopathogenesis of hepatitis C and hepatitis C treatment. A summary of major clinical research activities and faculty research interests is outlined below.
Hepatology
Clinical research efforts have been very active in this area, with ongoing trials of simtuzumab (anti-LOXL) from Gilead Sciences Inc. for advanced nonalcoholic steatohepatitis (NASH) cirrhosis. The division is among the highest enrollers in these trials.
In addition, it has seven clinical trials that are ongoing or near opening. For NASH, these include:
- An Immuron Ltd. trial that binds gut endotoxin.
- NGM 282, which is a partial fibroblast growth factor agonist.
- A toll-like receptor antagonist from Taiwan.
- Aramcol, a lipid agent that favorably alters fat metabolism from Galmed.
- A new Gilead Sciences protocol studying simtuzumab and an ASK-1 pathway inhibitor.
The division has recently completed the GenFit trial of a partial peroxisome proliferator-activated receptor alpha/delta agonist for NASH, and in the near future plans to participate in a primary sclerosing cholangitis trial. It is also considering participation in a protocol focused on severe alcoholic steatohepatitis (ASH), the acute variety of alcohol-related liver disease.
Inflammatory Bowel Disease (IBD)
The IBD group has several active phase III studies that are recruiting patients, including:
- Etrolizumab, a gut-selective integrin inhibitor that inhibits lymphocyte migration to the bowel.
- RPC1063, a modulator of S1P1R.
- GS-5746, a monoclonal antibody active against MMP-9.
- ABT-494, an oral JAK1 inhibitor.
Patients are also being followed in long-term extension trials involving vedolizumab, ustekinumab and the adalimumab registry.
Active phase III trials include:
- Etrolizumab vs. Placebo SC Therapy in Moderate to Severe UC (Roche GA29102 & GA28951) Naïve to TNF Antagonist Therapy and Surgery Evaluating the efficacy & safety of 10 Wk Induction & 52 Wk Maintenance of Etrolizumab (rhuMAb Beta 7 binding a4b7 & aEb7).
- Etrolizumab vs. Placebo SC Therapy in Moderate to Severe UC (Roche GA28950 & GA28951) Refractory or Intolerant to TNF Antagonist Therapy Blinded study evaluating the efficacy & safety of 10 Wk Induction & 52 Wk Maintenance.
- GS-5746 vs. Placebo SC Therapy in Moderate to Severe UC (Gilead GS US 326 1100) Naïve or Refractory/Intolerant to TNF Antagonist Therapy Evaluating GS-5746 SC (an Anti MMP-9 monoclonal antibody) with 8 Wk Induction & 44Wk Maintenance.
- RPC1063 vs. Placebo Oral Therapy in Moderate to Severe UC (Receptos RPC01 3101 & 3102) Naïve or Refractory/Intolerant to TNF Antagonist Therapy Evaluating RPC1063 (modulates S1P1R, reduces lymphocytes) w/12Wk Induction & 40Wk Maintenance.
- Etrolizumab vs. Placebo SC Therapy in Moderate to Severe CD (Roche GA29144 & GA29145) Naïve or Refractory/Intolerant to TNF Antagonist Therapy Evaluating the efficacy & safety of 14 Wk Induction & 60 Wk Maintenance.
- ABT-494 vs. Placebo Oral Therapy in Moderate to Severe CD (AbbVie Celest M13-740) Naïve or Refractory/Intolerant to TNF Antagonist Therapy Evaluating ABT-494 (JAK1 Inhibitor) w/16Wk Induction & 36Wk Maintenance.
- GS-5746 vs. Placebo SC Therapy in Moderate to Severe CD (Gilead GS US 395 1663) Naïve or Refractory/Intolerant to TNF Antagonist Therapy Evaluating GS-5746 with 8Wk Induction & 44Wk Maintenance (Brian Behm).