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
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