The aim of the present study is to increase our understanding of the cost effectivity and the pathophysiology underlying the beneficial effect of autologous SCT. We will investigate the immunological mechanisms involved in the (re)induction of…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To investigate on the cost effectivity and the immunological mechanisms
involved in immune reconstitution and engraftment after ASCT in Crohn's disease
patients. To gain insight in the effect of ASCT on the microbiome
Secondary outcome
Not applicable
Background summary
Crohn' disease is a complex disorder of the gastrointeinal tract that affects
over 35.000 patients in the Netherlands. Although available therapies are in
general effective, a small subgroup of patients is refractory to treatment and
are no candidates for surgery because of the risk of short bowel syndrome. ASCT
is a *last resort* for these CD patients who are refractory to any type of
therapy. Autologous SCT has been shown to induce dramatic and long-term
improvements in a range of autoimmune disorders in patients undergoing this
treatement for hematological malignancies. Also in Crohn's disease several
series have been published reporting succesful remission induction after ASCT.
The largest series has been reported bij Oyama et. al. in which twelve patients
with active Crohn's disease were treated with ASCT. After one and a half year
of follow up only one relapse was observed.
Although the underlying mechanisms remain largely unknown, immune
reconstitution after profound depletion appears to favor the development of
tolerance over pathogenic immunity. The first aim of the present study is to
increase our understanding of the pathophysiology underlying the beneficial
effect of autologous ASCT. We will investigate the immunological mechanisms
involved in the (re)induction of immune tolerance in the setting of autologous
ASCT. In addition by comparison of microbiome pre- and post transplantation we
aim to gain insight in the role of microbiota in the pathogenesis of acitve
Crohn*s disease in patients with refractoryCrohn*s disease.
Study objective
The aim of the present study is to increase our understanding of the cost
effectivity and the pathophysiology underlying the beneficial effect of
autologous SCT. We will investigate the immunological mechanisms involved in
the (re)induction of immune tolerance in the setting of autologous SCT. In
addition by comparison of microbiome pre- and post transplantation we aim to
gain insight in the role of microbiota in the pathogenesis of acitve Crohn*s
disease in patients with refractory Crohn*s disease.
Study design
Biomaterial (serum, DNA, feces, tissue) will be collected from patients
undergoing autologous stem cell transplantation for the treatment of Crohn's
disease.This is an open label, non-randomized, non-blinded, prospective study.
Patients will be recruited from the outpatient IBD clinics of the UMCU. Many
patients will be referrals from other centers. The ASCT will take place in the
st. Antonius Hospital. The expected recruitment is five patients per year.
Study burden and risks
The study related procedures for obtaining biomaterials (blood, fecal samples,
tissue samples during colonoscopy) involve no risk or burden except the
coloscopy with biopsy (risk of complicatiens is 0,3-1 per 1000)
Koekoekslaan 1
Nieuwegein 3435 CM
NL
Koekoekslaan 1
Nieuwegein 3435 CM
NL
Listed location countries
Age
Inclusion criteria
1) Age between 18 and 65 years
2) Confirmed diagnosis of active Crohn*s Disease:
3) Active disease at the time of registration to the trial
4) Unsatisfactory course despite 3 immunosuppressive agents (usually azathioprine, methotrexate and infliximab or adalimumab) in addition to corticosteroids. Patients should have relapsing disease (i.e. >1 exacerbation/year) despite thiopurines, methotrexate and/or infliximab/adalimumab maintenance therapy or clear demonstration of intolerance / toxicity to these drugs.
4) Current problems unsuitable for surgery or patient is at risk for developing short bowel syndrome.
Exclusion criteria
1) Pregnancy or unwillingness to use adequate contraception during the treatement, if a woman of childbearing age
2) Concomitant severe disease
a) renal: creatinine clearance < 40 ml/min (measured or estimated)
b) cardiac: clinical evidence of refractory congestive heart failure
c) psychiatric disorders including active drug or alcohol abuse
d) concurrent or recent history of malignant disease (excl. non-melanoma skin cancer)
e) uncontrolled hypertension, defined as resting systolic blood pressure >= 140 and/or resting diastolic pressure >= 90 despite at least 2 anti-hypertensive agents.
f) uncontrolled acute or chronic infection with HIV, HTLV-1 or 2, hepatitis viruses or any other infection the investigators consider a contraindication to participation.
g) other chronic disease causing significant organ failure, including established cirrhosis with evidence of impaired synthetic function on biochemical testing and known severe respiratory disease.
h) Crohn*s Disease symptoms predominantly due to fibrotic stricturing and unlikely to respond to immune manipulation.
3) Infection or risk thereof
a) History of tuberculosis or at current increased risk of tuberculosis
b) Mantoux test result or other investigations that the investigator as evidence of active tuberculosis.
c) Abnormal chest x ray (CXR) consistent with active infection or neoplasm.
4) Previous poor compliance
5) Concurrent enrolment in any other protocol using an investigational drug or hematopoietic growth factor up to four weeks before study entry.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL42003.100.13 |