A pilot, open-label, multicentre study to investigate the safety of calf intestine alkaline phosphatase in patients with fulminant active ulcerative colitis refractory to steroid therapy

ISRCTN	ISRCTN64619216
DOI	https://doi.org/10.1186/ISRCTN64619216
Secondary identifying numbers	N/A

Submission date: 07/06/2006
Registration date: 07/06/2006
Last edited: 07/09/2011

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Digestive System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr B.Th.M. Bierman
Scientific

AM-Pharma B.V.
Rumpsterweg 6
Bunnik
3981 AK
Netherlands

Phone	+31 (0)30 2289222
Email	B.Bierman@AM-Pharma.com

Study information

Study design	A pilot, open-label, non-randomized, multicentre study
Primary study design	Interventional
Secondary study design	Non randomised controlled trial
Study setting(s)	Not specified
Study type	Treatment
Scientific title
Study acronym	AP IBD 02-01
Study objectives	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(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	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
Primary outcome measure	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 study start date	06/12/2006
Completion date	31/12/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	20
Key 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
Key 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
Date of first enrolment	06/12/2006
Date of final enrolment	31/12/2007

Locations

Countries of recruitment

Netherlands

Study participating centre

AM-Pharma B.V.

Bunnik
3981 AK
Netherlands

Sponsor information

AM-Pharma B.V. (The Netherlands)
Industry

Rumpsterweg 6
Bunnik
3981 AK
Netherlands

"ROR"	https://ror.org/02bpbnv34

Funders

Funder type

Industry

AM-Pharma B.V.

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan