Condition category
Digestive System
Date applied
07/06/2006
Date assigned
07/06/2006
Last edited
07/09/2011
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr B.Th.M. Bierman

ORCID ID

Contact details

AM-Pharma B.V.
Rumpsterweg 6
Bunnik
3981 AK
Netherlands
+31 (0)30 2289222
B.Bierman@AM-Pharma.com

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Acronym

AP IBD 02-01

Study hypothesis

Ulcerative colitis (UC) is characterized by abnormal activation of the colon epithelium, which is considered to be a central pathogenic mechanism. Activation of colon epithelium cells in UC is associated with an abnormally high expression of Toll-like receptors (TLR), including TLR-4, the major transducer of lipopolysaccharide (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
2. Prevent systemic inflammatory responses that result from transmigration of endotoxin though the leaky inflamed intestinal mucosa.
Therefore, it is expected that administration of calf intestine alkaline phosphatase (CIAP) may attenuate or prevent the local and systemic inflammatory response in patients with fulminant ulcerative colitis.

Ethics approval

Not provided at time of registration

Study design

A pilot, open-label, non-randomized, multicentre study

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Fulminant ulcerative colitis

Intervention

Subjects will receive 30,000 U alkaline phosphatase per 24 hr for 7 consecutive days via a duodenal catheter.

Intervention type

Other

Phase

Not Specified

Drug names

Primary outcome measures

Safety and tolerability

Secondary outcome measures

1. Rescue medication including cyclosporin,
experimental medication such as anti-CD-3 antibodies or colectomy rate at 9 weeks (63 days)
2. Clinical response based on change in the MTWSI for disease activity between baseline - day 15 - clinical, endoscopical and serological activity scores at baseline and after 1 week of treatment, including the Modified Truelove and Witts Severity Index, the Mayo score, colon biopsy samples
3. CRP plasma levels and stool markers of disease activity (calprotectin)

Overall trial start date

06/12/2006

Overall trial end date

31/12/2007

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients between 18 and 70 years (inclusive)
2. A diagnosis of UC verified by colonoscopy and confirmed by histology
3. Active disease documented by a Modified True Love and Witts Severity Index (MTWSI) score of 11-21, despite an ongoing treatment course of intravenous steroids for a minimum of 3 days prior to the study; a stool frequency >8 stools or a stool frequency between 3 and 8 and a C-reactive protein (CRP) >45 mg/l (Travis criteria)
4. Women of childbearing potential who have a negative serum pregnancy test at baseline screening
5. Patients must have tested negative for stool cultures including Clostridium difficile
6. Patients who are capable of understanding the purpose and risks of the study and who provide a signed and dated written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

20

Participant exclusion criteria

1. UC requiring immediate surgical, endoscopic, or radiological interventions, including massive hemorrhage, perforation and sepsis, suppurative complications (intra-abdominal or peri-anal abscesses) or toxic colon
2. History of large bowel surgery
3. Patients with serious infections
4. Significant organ dysfunction
5. Pregnant women or nursing mothers
6. Concomitant medications:
a.. Altered dose of any 5-aminosalicylates (5-ASA) preparation within two weeks of screening
b. Altered dose of azathioprine or mercaptopurine within four weeks of screening
c. Patients who have started azathioprine in the last three months prior to baseline
d. Received probiotic, antibiotics or cyclosporine within 1 month or 2 months respectively prior of screening
e. Received any experimental treatment for this population e.g. infliximab, tacrolimus, (FK506) within two months of screening

Recruitment start date

06/12/2006

Recruitment end date

31/12/2007

Locations

Countries of recruitment

Netherlands

Trial participating centre

AM-Pharma B.V.
Bunnik
3981 AK
Netherlands

Sponsor information

Organisation

AM-Pharma B.V. (The Netherlands)

Sponsor details

Rumpsterweg 6
Bunnik
3981 AK
Netherlands

Sponsor type

Industry

Website

Funders

Funder type

Industry

Funder name

AM-Pharma B.V.

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes