Inflammatory Disorders: Inflammatory Bowel Diseases (IBD) – Crohn’s and Ulcerative Colitis (UC) and Others
- The systemic inflammatory response
- sepsis
- vasculitis
- neurodegenerative disease
- cancer immunology
- autoimmune diseases: rheumatoid arthritis, colitis, ileitis, …
- T cells in immunity
SOURCES
Inflammatory Disorders: Articles published @ pharmaceuticalintelligence.com
Curators: Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
Biology, Physiology and Pathophysiology of Heat Shock Proteins
Curation: Larry H. Bernstein, MD, FCAP
Heat Shock Proteins (HSP) and Molecular Chaperones
Curator: Larry H. Bernstein, MD, FCAP
https://pharmaceuticalintelligence.com/2016/04/13/heat-shock-proteins-and-molecular-chaperones/
LPBI Group’s Inflammation Drug Discovery and Positioning Project
Curator: Aviva Lev-Ari, PhD, RN
Autoimmune Inflammtory Bowel Diseases: Crohn’s Disease & Ulcerative Colitis – Potential Roles for Modulation of Interleukins 17 and 23 Signaling for Therapeutics
Curators: Larry H Bernstein, MD FCAP and Aviva Lev-Ari, PhD, RN
Cytokines in IBD
Curators: Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2016/02/13/cytokines-in-ibd/
Collagen-binding Molecular Chaperone HSP47: Role in Intestinal Fibrosis – colonic epithelial cells and subepithelial myofibroblasts
Curators: Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
IBD: Immunomodulatory Effect of Retinoic Acid – IL-23/IL-17A axis correlates with the Nitric Oxide Pathway
Curators: Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
Intestinal inflammatory pharmaceutics
Curator: Larry H. Bernstein, MD, FCAP
http://pharmaceuticalintelligence.com/2016/02/11/intestinal-inflammatory-pharmaceutics/
How could we develop such capabilities — what type of relations should we explore with the Cambridge, MA company
http://pharmaceuticalintelligence.com/2016/02/11/intestinal-inflammatory-pharmaceutics/
Multi-Functional Anti-Inflammatory Drugs (MFAIDs): Small Molecule Invention of Dr. Saul Yedgar, HUJI and Yissum
Reporters: Larry H Bernstein and Aviva Lev-Ari, PhD, RN
Clinicaltrials.gov
Curator: Stuart Cantor, PhD
Search “inflammation” and “phase 3” and disease state ”IBD”, “Cirrhosis”, “Celiac disease”
Inflammatory Bowel Disease (IBD)
Title/Sponsor | Purpose | Drug(s) | Comments |
Effects of Prednisolone and Infliximab on the Regulation of Urea Synthesis in Active Inflammatory Bowel Disease
University of Aarhus, Denmark |
Loss of total mass of muscles (catabolism) is a serious clinical problem in patients with active inflammatory bowel disease (IBD). The investigators have earlier shown that the liver plays an important role in this stress-catabolism by increasing the production of urea during the inflammatory process.
The purpose of this study is to examine the effect of the anti-inflammatory drugs prednisolone and infliximab on the regulation of the urea synthesis in patients with active ulcerative colitis and Crohn’s disease. |
Prednisolone and Infliximab | **STUDY COMPLETED** |
Safety and Tolerability Of Allogeneic Mesenchymal Stromal Cells in Pediatric Inflammatory Bowel Disease
Catherine Bollard, Children’s Research Institute |
Investigators will infuse donor bone marrow mesenchymal stromal cells intravenously, as a treatment for pediatric Crohn’s disease that has not responded to conventional therapies. The goals of this study are to test the safety and tolerability of donor mesenchymal stromal cells in children with Inflammatory Bowel Disease.
Mesenchymal stromal cells support the development of blood cells within the bone marrow. When isolated from a donor and infused into an animal or human, they have been demonstrated to travel to areas of inflammation, to alter immune responses, to decrease pro-inflammatory cytokines, and to promote tissue repair. Infusion of these cells does not lead to rejection. These properties lead investigators to hypothesize that that these may be they may be beneficial in treating IBD. |
Allogeneic bone marrow-derived mesenchymal stromal cells | Phase 1 |
Effects of Naltrexone on Active Crohn’s Disease Penn State University |
It is hypothesized that the opioid antagonist naltrexone will improve inflammation of the bowel and quality of life in subjects with active Crohn’s disease compared to placebo. |
Naltrexone |
STUDY COMPLETED |
Anti- Inflammatory Effects of Mango Polyphenolics in Inflammatory Bowel Disease
Texas A&M University |
Bioactive compounds from mango are bioavailable and their anti-inflammatory efficacy has been demonstrated in animals and humans. However, the efficacy of mangoes has not previously been compared with respect to mild inflammatory bowel disease. In order to justify future pharmacokinetic and pharmacodynamic analyses in human clinical trials, a pilot assessment to determine efficacy in preventing or resolving Inflammatory bowel disease is a necessary step. Therefore, in this aim we will determine the clinical relevance of mango as an adjuvant treatment to conventional therapy in Inflammatory bowel disease . The effects of mango with common drug treatment in mild-moderate Inflammatory bowel disease will be compared to the drug-treatment alone. | Mango polyphenolics Dietary Supplement: sugary beverage |
This study is currently recruiting participants. Estimated Study Completion DATE: May 2016
Infliximab to Treat Crohn’S-like Inflammatory Bowel Disease in Chronic Granulomatous Disease
This study will determine if the drug infliximab is safe for treating inflammatory bowel disease (IBD) in patients with chronic granulomatous disease (CGD). IBD is an inflammation or irritation of the gut that leads to symptoms such as diarrhea, bloating and stomach cramps. CGD is an inherited disease affecting white blood cells called neutrophils in which patients are susceptible to repeated bacterial and fungal infections. They also have a higher incidence of some autoimmune diseases, such as IBD. Infliximab is approved to treat Crohn’s disease, an IBD similar to that seen in patients with CGD.
InfliximabThis study has been completed.
Pilot Study of Green Tea Extract (Polyphenon E) in Ulcerative Colitis
University of Louisville
Green tea consists of several components, with most research focusing on the polyphenol fraction. The polyphenol fraction(-)-epigallocatechin-3-gallate (EGCG)has been studied extensively as an anti-inflammatory agent as well as a preventative agent for cancer. It has been shown to effectively reduce the inflammation associated with animal models of inflammatory bowel disease. This clinical trial will determine the ability of EGCG, in the form of Polyphenon E®, to treat patients with mild to moderately severe ulcerative colitis.
Green tea extract
green tea polyphenol extracts manufactured by the Mitsui Norin Co., Ltd. of Japan
This study has been completed.
Casein Glycomacropeptide in Active Distal Ulcerative Colitis (Pilot Study)
University of Aarhus
Casein glycomacropeptide (CGMP) has anti-inflammatory properties in experimental rodent colitis and using human in vitro inflammation models. Its use as a food ingredient has proven safe and with no influence on dietary intake. We hypothesize that orally administered CGMP has a beneficial effect comparable to that of mesalazine in active distal ulcerative colitis.
Drug: CGMP protein
powder dissolved in 300 ML water once daily
Drug: Maximal oral 5ASA
4800 grams/day of Mesalazine (Asacol/Mezavant)
This study has been completed.
G-CSF to Treat Crohn’s Disease
National Institute of Allergy and Infectious Diseases (NIAID)
Evaluate the immunologic and the clinical response to granulocyte-colony stimulating factor (G-CSF, Filgrastim, Neupogen) administered to patients with Crohn’s Disease.
This study will examine the effectiveness of G-CSF in treating patients with Crohn’s disease-a long-term recurring inflammation of the small and large intestine. Patients may have swelling and bleeding of the intestinal lining, which can lead to infection and abdominal pain, weight loss, fever, diarrhea, bloody stools, fistula (connections between the skin and intestine), intestinal blockages, and abscesses. Although there are various treatments for Crohn’s disease, many patients continue to have inflammation that is difficult to control or severe side effects from the medications. G-CSF is an approved drug that is used to increase white blood cell counts. Other cells, immune cells, exposed to G-CSF can develop a specific immune action-a Th-2 response-that decreases the inflammatory response in Crohn’s disease-a Th-1 response.
Filgrastim,
Neupogen
This study has been completed.
Dose Escalation and Remission
James Lewis, University of Pennsylvania
The proposed study will test whether increasing Lialda dose can reduce fecal calprotectin (FCP) levels, a marker of intestinal inflammation that is highly predictive of the risk of relapse among patients with quiescent ulcerative colitis. Sixty patients with FCP levels <50µg/g stool will be observed for 48 weeks. A ll patients will have FCP concentration measured using a commercially available assay at enrollment, 6 weeks and 12 weeks. All patients with persistently elevated FCP will receive one or both of the following interventions: change in the mesalamine formulation to Lialda and/or increase in the dose of Lialda. Reduction in FCP levels below 50µg/g stool 6 weeks after randomization will be the primary outcome.mesalamineThis study has been completed.
Visilizumab for Moderate to Severe Inflammatory, Nonstricturing, Nonpenetrating Crohn’s Disease
The purpose of the study is to evaluate an intravenous (by injection) investigational medication to treat moderate to severe inflammatory, nonstricturing, nonpenetrating Crohn’s disease. The research is being conducted at up to 5 clinical research sites in the US and Europe and is open to both men and women ages 18 to 70 years old. Participants in the study will have a number of visits to a research site up to 17 months
Visilizumab (a humanized antibody)This study has been completed.
Cirrhosis: “inflammation” and “cirrhosis” and “phase 3”
Title/Sponsor | Purpose | Drug | Phase/Comments |
Phase 3 Study of Obeticholic Acid Evaluating Clinical Outcomes in Patients With Primary Biliary Cirrhosis (COBALT)
Intercept Pharmaceuticals |
OCA is a modified bile acid and bile acid or Farnesoid X receptor (FXR) agonist that is derived from the primary human bile acid chenodeoxycholic acid. The key mechanisms of action of OCA, including its choleretic, anti-inflammatory, and anti-fibrotic properties, underlie its hepatoprotective effects and result in attenuation of injury and improved liver function in a cholestatic liver disease such as PBC. The study will assess the effect of OCA compared to placebo, combined with stable standard care, on clinical outcomes in Primary Biliary Cirrhosis (PBC) patients. | Obeticholic Acid (OCA) | Phase 3
The primary functions of FXR activation is the suppression of cholesterol 7 alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis from cholesterol. FXR does not directly bind to the CYP7A1 promoter. Rather, FXR induces expression of small heterodimer partner (SHP), which then functions to inhibit transcription of the CYP7A1 gene. In this way a negative feedback pathway is established in which synthesis of bile acids is inhibited when cellular levels are already high. FXR has also been found to be important in regulation of hepatic triglyceride levels. |
Safety and Efficacy Study of Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis
University of Tennessee |
Primary sclerosing cholangitis (PSC), although uncommon, is a devastating and insidiously progressive liver disease, resulting from advancing inflammation, fibrosis and obliteration of the bile ducts in the liver, leading to cirrhosis and end-stage liver disease. Although prognosis in children may be somewhat better than that of adults, approximately one third of pediatric patients require transplantation by adulthood. Other than transplantation, there is to date no therapy conclusively proven to improve the long-term outcome. Ursodeoxycholic acid (UDCA) improves biochemical markers of liver disease, although in high doses does not clearly improve the long-term outcome in adults, and in a recent study may have actually worsened outcome. Childhood PSC is different from that of adult PSC in many ways, and children may derive more short-term, as well as long-term, benefit than adults. This unique multicenter study will carefully monitor the effects of withdrawal and restarting UDCA on liver injury and inflammation in children with PSC. The preliminary data will help in the design of a more definitive larger study to determine if UDCA has a beneficial role in the treatment of PSC in children. | ursodeoxycholic acid (UDCA) | Phase 1 |
Study of the Effect of Adjunctive Vivomixx® in Addition to Antibiotics on Systemic and Cerebral Inflammatory Response in Patients With Cirrhosis and Spontaneous Bacterial Peritonitis (SBP)
Fundació Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, Barcelona, Spain |
Objectives: To assess the effect of adjunctive Vivomixx® on bacterial translocation in patients with cirrhosis and SBP. The main Inclusion Criteria: Patients with cirrhosis hospitalized with an episode of SBP at the hospital.
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Vivomixx® |
Phase 3
Vivomixx® is a probiotic mixture of 8 proprietary strains. It will be supplied as a 4.4 g sachet at a dose of 450 billion live bacteria per sachet with maltose and silicon dioxide as excipients. This study will have 30 patients and run for 2 years. |
Albumin Administration in Cirrhotic Patients w/Bacterial Infection & a Systemic Inflammatory Response Syndrome Unrelated to Spontaneous Bacterial Peritonitis
Centre Hospitalier Universitaire de Besancon, France |
Spontaneous bacterial peritonitis (SBP) is the most frequent infection and induces severe circulatory dysfunction associated with renal failure in about 30% of cases. Renal failure is a reliable surrogate marker of in-hospital mortality in patients with SBP or with non-SBP infections. Albumin, as an adjuvant to antibiotherapy reduces significantly the rate of renal failure, in-hospital mortality, and overall mortality (Sort P, et al. NEJM 1999). However, little is known regarding the effect of albumin administration in patients with non-SBP infections. Two recent prospective studies demonstrated that non-SBP infections are associated with impairment of the effective circulating volume and precipitate renal failure whatever the presence of ascites.The aim of this randomized clinical trial is to evaluate the effects of albumin, associated with appropriate antibiotic therapy, on occurrence or deterioration of renal failure and survival in septic (SIRS criteria required) cirrhotic patients with non-SBP infections and presenting with a Child-Pugh score > 8. | Albumin | Phase 3.Study terminated- decision of independent monitoring committee. Risk of death at 3 months higher in Albumin group than in control group, without reaching significance level. |
Anti-Fibrotic Effects of Losartan in non-alcoholic steatohepatitis (Nash) Evaluation Study
Newcastle-upon-Tyne Hospitals, UK |
Liver fibrosis is the accumulation of tough, fibrous scar tissue in the liver which occurs in patients with NASH. NASH resembles alcoholic liver disease, but occurs in people who drink little or no alcohol. The major feature in NASH is fat in the liver, along with inflammation and damage, which may lead to cirrhosis, in which the liver is permanently damaged and scarred and no longer able to function properly. | Losartan | Phase 3 |
Omega 3 Fish Oil Supplements vs. Placebo for Patients With Non-alcoholic Steatohepatitis (NASH)
University of Virginia |
Nonalcoholic steatohepatitis (NASH) occurs in 2-3% of the US population and carries a 15-20% chance of progression to cirrhosis. It is closely associated with obesity, hyperlipidemia and insulin resistance. Therapy usually includes recommendations to increase exercise and to begin weight reducing diets but these goals are variably achieved and their relative effects in conjunction with pharmacological intervention have not been well defined. Moreover, these lifestyle changes can confound results of treatment trials if not quantified through conditioning testing and measures of body fat. Polyunsaturated fatty acids, especially formulation rich in omega-3, are widely accepted and endorsed in the medical community for their beneficial effects on hyperlipidemia and coronary disease risk reduction. Recent data suggests that omega-3 fatty acids ameliorate hepatic steatosis in humans and in animal models of NASH by reducing hepatic fat content. We hypothesize that a one year course of omega-3 fatty acid (3gm/day) will produce improvement in NASH histological injury independent of changes in weight (BMI) or degree of conditioning measured by the lactate threshold. The effects of the supplement will be compared to a placebo group and controlled for these lifestyle changes. | Omega 3 Fish Oil supplements | Phase 3 (with placebo) |
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Prevention of Disease Progress in Chronic Hepatitis C Patients With Liver Fibrosis
Merck Sharp & Dohme Corp. |
The objective of the study is to evaluate the safety and efficacy of PEG-Intron versus no treatment for the prevention of fibrosis progression in adult participants with moderate to severe liver fibrosis secondary to chronic hepatitis C, who failed PEG-Intron plus Rebetol treatment in protocol P02370 (NCT00039871). | Peginterferon alfa-2b PEG-Intron 0.5 µg/kg weekly subcutaneously as maintenance therapy for 36 months with 4-week follow-up. | **STUDY COMPLETED** |
“Inflammation” and “Celiac disease”
Sponsor | Purpose | Drug/Arms | Comments/Phase |
Celimmune | randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of AMG 714 for the attenuation of the effects of gluten exposure in adult patients with celiac disease during a gluten challenge. | AMG 714 (biologic)
fully human anti-IL-15 monoclonal antibody
150 or 300 mg SC every 2 weeks |
Phase 2a, posted 12/15 (not started yet) |
ChemoCentryx
|
Evaluation of the effect of CCX282-B compared to placebo on the villous height/crypt depth ratio of small intestinal biopsy specimens taken from subjects with celiac disease, before and after gluten exposure. | CCX282-B
vercirnon is a specific, orally-administered chemokine receptor CCR9 antagonist. 250mg capsule, twice daily, 13 weeks |
Phase 2 . This drug targets the chemokine receptor known as CCR9, and used for the potential treatment of patients with moderate-to-severe Crohn’s disease |