The aim of this study is to determine the safety and effectiveness of extracorporeal photopheresis (ECP) to induce a clinical response in Crohn's disease patients who have failed treatment with immunosuppressants or anti-TNF agents. Existing experience supports the use of ECP in Crohn's disease as it has been successful in allowing steroid-dependent Crohn's patients to decrease or eliminate steroid use. The study design consists of a twelve week course of treatment with two weekly (weeks 0-4) and then two bi-weekly ECP (weeks 6, 8, 10, and 12) session with data collected on adverse events and clinical response as measured by the Crohn's disease Activity Index (CDAI). There is a 4 week follow-up phase following the last ECP treatment. Outcomes will include the rates of adverse events and proportion of responders (a fall in the CDAI score of greater than or equal to 100 points) at each treatment week.

The purpose of this sub study is to determine changes in the immune response that attend a clinical response during and after ECP treatment. We will assay for changes in cytokine production and immune cell populations in white blood cells in the peripheral blood and the lining of the inflamed colon. To do this we obtain additional blood samples at baseline, week 6, 12, and at the end of follow-up and will obtain gut mucosal biopsies at baseline and week 12. Cells purified from these samples will be assayed for cytokine secretion, regulatory T cell activity, and lymphocyte and dendritic cell phenotyping.

Treatment or Intervention	Phase
Drug: Uvadex	Phase II

Further Study Details: 

Expected Total Enrollment:  4

The aim of this study is to determine the safety and effectiveness of extracorporeal photopheresis (ECP) to induce a clinical response in Crohn's disease patients who have failed treatment with immunosuppressants or anti-TNF agents. Existing experience supports the use of ECP in Crohn's disease as it has been successful in allowing steroid-dependent Crohn's patients to decrease or eliminate steroid use. The study design consists of a twelve week course of treatment with two weekly (weeks 0-4) and then two bi-weekly ECP (weeks 6, 8, 10, and 12) session with data collected on adverse events and clinical response as measured by the Crohn's disease Activity Index (CDAI). There is a 4 week follow-up phase following the last ECP treatment. Outcomes will include the rates of adverse events and proportion of responders (a fall in the CDAI score of greater than or equal to 100 points) at each treatment week.

The purpose of this sub study is to determine changes in the immune response that attend a clinical response during and after ECP treatment. We will assay for changes in cytokine production and immune cell populations in white blood cells in the peripheral blood and the lining of the inflamed colon. To do this we obtain additional blood samples at baseline, week 6, 12, and at the end of follow-up and will obtain gut mucosal biopsies at baseline and week 12. Cells purified from these samples will be assayed for cytokine secretion, regulatory T cell activity, and lymphocyte and dendritic cell phenotyping.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
To be eligible, patients must have passed the same screening criteria as for the main protocol but with more stringent platelet level requirements:
Signed and dated consent form for main protocol and substudy protocol must be obtained prior to conducting any study procedure.
Patients must be greater than or equal to 18 years of age.
Patients must weight greater than or equal to 40 kg (88 lb).
Patients must have had Crohn's disease for at least 6 months' duration, with ileitis, colitis, or ileocolitis confirmed by radiography or endoscopy.
Patients must have a CDAI greater than or equal to 220 to less than 450.
Patients must have a CRP greater than 10.0 mg/L.
Patients taking steroids must be on a prednisone equivalent less than 25 mg/d or an oral budesonide dose less than 9 mg/d.
Concomitant medications may include:
-any stable dose of aminosalicylates, antibiotics, or immunosuppressants (6-MP, AZA, or MTX, e.g.) for at least 4 weeks.
-corticosteroids or p.o. budesonide for at least 2 weeks.
-anti-TNF agents (infliximab or adalimumab) for at least 8 weeks.
Patients must have a history of failed response or intolerance to treatment with immunosuppressants or anti-TNF agents. A failed response is the persistence of active Crohn's symptoms despite prior or current treatment with at least one of the following:
Azathioprine 2-3 mg/kg for 12 weeks;
6-MP 1.0-1.5 mg/kg/d for 12 weeks;
Methotrexate 25 mg/wk for 8 weeks;
Infliximab greater than or equal to 5 mg/kg for 4 weeks (i.e. at least one infusion);
Adalimumab greater than or equal to 40 mg SC for 4 weeks (i.e. at least two injections);
Intolerance to immunosuppressants or anti-TNF agents is experiencing side effects related to at least one of the agents listed above at Grade 2 or higher according to the Common Toxicity Criteria that limit or proscribe their use at doses needed to adequately control the activity of the patients' Crohn's disease.
Patients discontinuing therapies prior to enrolling must have done so by the following times:
-Antibiotics, aminosalicylates, corticosteroids or PO budesonide for at least 2 weeks.
-Immunosuppressants or anti-TNF agents for at least 8 weeks.
-Other investigational agents or non-biologics for at least 4 weeks and other biologics for at least 8 weeks.
Patients may have fistulae if they also have predominantly luminal Crohn's disease and the fistulae are not associated with abscess formation.
Patients must have a platelet count greater than or equal to 100,000/micro L.
Female patients must be postmenopausal, surgically incapable of bearing children, or practicing an acceptable method of birth control (hormonal contraceptives, intrauterine devices, spermicide and barrier, for instance). Abstinence or partner/spouse sterility may also qualify at the Investigator's discretion. Female patients of child-bearing potential must have a negative urine pregnancy test at screening.
Patients must be able and willing to comply with all main protocol and substudy procedures.
EXCLUSION CRITERIA:
Patients who are concomitantly using biologic agents other than anti=TNF agents, cyclosporine, tacrolimus, mycophenylate mofetil, or investigational Crohn's therapies.
Patients who in the opinion of the Investigator may not be able to stay on a stable dose of concomitant Crohn's disease medication for at least 12 weeks.
Patients with currently symptomatic untreated diarrhea due to conditions other than inflammatory Crohn's disease (e.g. bacterial or parasitic gastroenteritis, bile salt diarrhea, or bacterial overgrowth).
Patients with symptomatic intestinal strictures.
Patients with stomas.
Patients with other local manifestations of Crohn's disease such as abscesses, or other disease manifestations for which surgery might be indicated, or which might preclude utilization of a CDAI to assess response to therapy (such as short gut syndrome).
Patients who are unable to tolerate the extracorporeal volume shifts associated with ECP treatment due to the presence of any o the following conditions: Uncompensated congestive heart failure, pulmonary edema, severe chronic obstructive pulmonary disease, severe asthma, renal failure, hepatic failure.
Patients receiving TPN as the sole source of nutrition within the three weeks of screening.
Female patients whose hemoglobin is less than 8.5 g/dL or male patients who hemoglobin is less than 10 g/dL at the first screening visit.
Patients with a poor tolerability of venipuncture or a lack of adequate venous access for required treatments and blood sampling.
Patients who have a known hypersensitivity or allergy to psoralen (methoxsalen).
Patients who have a known hypersensitivity or allergy to both heparin and citrate products.
Female patients who are pregnant and/or lactating.
Patients who have been enrolled in any investigational study for the treatment of Crohn's disease within 4 weeks of enrollment for non-biologic therapies and within 8 weeks of enrollment for biologic therapies.
Patients with platelet count less than 100,000/micro L or PT INR greater than 1.3 or PTT greater than 3 sec control.

Maryland
      National Institute of Allergy and Infectious Diseases (NIAID), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  050108; 05-I-0108
Record last reviewed:  February 17, 2005
Last Updated:  March 10, 2005
Record first received:  March 10, 2005
ClinicalTrials.gov Identifier:  NCT00105261
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08