Safety/Efficacy Study of Bovine Intestinal Alkaline Phosphatase in Patients With Moderate to Severe Ulcerative Colitis

NCT00727324 | Completed Phase 2 DMC

• 1 other identifier: AP IBD 02-02
• Study Type: interventional
• Target: 22
• Locations: 2 countries
• Sites: 11

Brief Summary

Ulcerative colitis is characterized by abnormal activation of, and damage to, the colon epithelium, which is considered to be a central pathogenic mechanism. Activation of colon epithelium cells in UC is associated with an abnormal high expression of Toll-like receptors, including TLR-4, the major transducer of LPS, binding specifically the lipid A portion of LPS. Alkaline Phosphatase binds and subsequently dephosphorylates LPS, thereby eliminating the ability of LPS to activate TLR-4. This is expected to 1) prevent activation of the intestinal epithelium and 2) prevent systemic inflammatory responses that result from transmigration of endotoxin though the leaky inflamed intestinal mucosa. Therefore, it is expected that administration of BIAP may attenuate or prevent the local and systemic inflammatory response in patients with severe ulcerative colitis.

Conditions

Ulcerative Colitis

Keywords

Ulcerative Colitis; UC; moderate; severe; LPS; Alkaline Phosphatase; AP; BIAP; Mucositis

Outcome Measures

Primary Outcomes (1)

• Investigate the safety and tolerability of 7 days of BIAP administration in subjects with moderate to severe ulcerative colitis

  28 days

Secondary Outcomes (2)

• To evaluate the efficacy of 7 days of BIAP administration in subjects with moderate to severe ulcerative colitis

  63 days (9 weeks)

• To evaluate the efficacy of 7 days of BIAP administration on related variables in subjects with moderate to severe ulcerative colitis

  63 days (9 weeks)

Study Arms (1)

1

EXPERIMENTAL

BIAP

Drug: bovine intestinal alkaline phosphatase (BIAP)

Interventions

bovine intestinal alkaline phosphatase (BIAP) DRUG

30,000U/24h for 7 consecutive days via a duodenal catheter

Also known as: BIAP, AP

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age, \>18 years, AND
• Capable of understanding the purpose and risks of the study and have provided a signed and dated written IC, AND
• Prior to the study baseline, been treated with oral steroid medication, of which \> 2 weeks on oral prednisone equivalent of at least 40mg/day, and still have:
• active ulcerative colon disease documented by a MAYO score of 6-11, and
• active ulcerative colon disease documented by a MTWSI score of 7-15
• Prior to the study baseline, documented clinical inability to decrease or stop the course of oral steroid medication. Subjects have been treated for a minimum of 12 weeks, and still have:
• chronic active ulcerative colon disease documented by a MAYO score of 6-11, and
• chronic active ulcerative colon disease documented by a MTWSI score of 7-15
• Prior to the study baseline, been treated with a stable dosage of azathioprine for a minimum of 12 weeks, and have a moderate to severe relapse defined as:
• chronic active ulcerative colon disease documented by a MAYO score of 6-11, and
• chronic active ulcerative colon disease documented by a MTWSI score of 7-15.

You may not qualify if:

• UC, requiring immediate surgical, endoscopic, or radiological intervention; including massive haemorrhage, perforation and sepsis, suppurative complications (intra-abdominal or peri-anal abscesses) or toxic colon,
• history of large bowel surgery,
• history of serious infections,
• positive stool cultures, including Clostridium difficile,
• significant organ dysfunction,
• pregnancy, nursing mothers, or women of childbearing potential without appropriate use of contraceptives,
• treatment with:
• an altered dose of any 5-ASA preparation within 4 weeks of screening,
• an altered dose of azathioprine or mercaptopurine within 4 weeks of screening (stable dosage of immunosuppressives is allowed), or start of azathioprine in the last 3 months prior to baseline,
• probiotics, antibiotics within 1 month, methotrexate or cyclosporine within 2 months prior to screening,
• any experimental treatment for this population e.g. infliximab, tacrolimus, FK506 or other anti TNFα therapy) within 2 months of screening.

Sponsors & Collaborators

• AM-Pharma: lead
• CRM Biometrics GmbH: collaborator
• Sintesi Research Srl: collaborator
• Vigilex BV: collaborator

Study Sites (11)

Internal Clinic, Vitkovice Hospital Ostrava

Ostrava, Vitkovice, 703 84, Czechia

Location

Teaching Hospital Olomouc, Dep. Internal Clinic

Olomouc, 775 20, Czechia

Location

Center of Gastroenterology at General Teaching Hospital

Prague, 120 00, Czechia

Location

Institute of Clinical and Preventive Medicine (IKEM), Clinic of Hepatogastroenterology

Prague, 40 21, Czechia

Location

Università di Ancona - Nuovo Complesso Didattico, Facoltà di Medicina e Chirurgia, Clinica di Gastroenterologia

Ancona, Torrette, 60020, Italy

Location

University of Bologna, Dept of Internal Medicine and Gastroenterology

Bologna, I-40138, Italy

Location

Ospedale di Marsciano, Ambulatorio Gastroenterologia

Marsciano, 06055, Italy

Location

Ospedale Santa Maria delle Croci, Servizio di Gastroenterologia e Endoscopia Digestiva

Ravenna, 48100, Italy

Location

Università Cattolica di Roma, Dipartimento di Medicina Interna

Roma, 00168, Italy

Location

Azienda Ospedaliera S. Camillo - Forlanini

Roma, I-00152, Italy

Location

Ospedale Mauriziano, UOA Gastroenterologia

Torino, 10128, Italy

Location

Related Publications (4)

• Poelstra K, Bakker WW, Klok PA, Kamps JA, Hardonk MJ, Meijer DK. Dephosphorylation of endotoxin by alkaline phosphatase in vivo. Am J Pathol. 1997 Oct;151(4):1163-9.

  PMID: 9327750 BACKGROUND

• Nakamura M, Saito H, Kasanuki J, Tamura Y, Yoshida S. Cytokine production in patients with inflammatory bowel disease. Gut. 1992 Jul;33(7):933-7. doi: 10.1136/gut.33.7.933.

  PMID: 1644332 BACKGROUND

• Brynskov J, Nielsen OH, Ahnfelt-Ronne I, Bendtzen K. Cytokines (immunoinflammatory hormones) and their natural regulation in inflammatory bowel disease (Crohn's disease and ulcerative colitis): a review. Dig Dis. 1994 Sep-Oct;12(5):290-304. doi: 10.1159/000171464.

  PMID: 7882549 BACKGROUND

• Lukas M, Drastich P, Konecny M, Gionchetti P, Urban O, Cantoni F, Bortlik M, Duricova D, Bulitta M. Exogenous alkaline phosphatase for the treatment of patients with moderate to severe ulcerative colitis. Inflamm Bowel Dis. 2010 Jul;16(7):1180-6. doi: 10.1002/ibd.21161.

  PMID: 19885903 RESULT

Related Links

• AM-Pharma Homepage

MeSH Terms

Conditions

Colitis, Ulcerative; Lymphoma, Follicular; Mucositis

Interventions

2-(3',4'-dihydroxyphenyl-1-azo)benzimidazole

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Mouth Diseases; Stomatognathic Diseases

Study Officials

• Prof Milan Lukas, PhD, MD

  University Prague, Czech Republic

  PRINCIPAL INVESTIGATOR

• Prof Paolo Gionchetti, PhD, MD

  Policlinico S. Orsola, Bologna, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: July 30, 2008
• First Posted: August 1, 2008
• Study Start: May 1, 2006
• Primary Completion: November 1, 2006
• Study Completion: December 1, 2006
• Last Updated: April 2, 2012

Record last verified: 2012-03

Locations

CZ (4); IT (7)