Bone Marrow Stromal Cells for Inflammatory Bowel Diseases
- Bone marrow stromal cells (BMSCs) are cells that can develop into other tissue types, including bone, cartilage, marrow, and blood cells. However, BMSCs are not stem cells there is no evidence that after infusion into another person that BMSCs change into any other cells. Research suggests that BMSCs can travel to different parts of the body and work with immune cells to reduce inflammation and help repair damaged tissues. BMSC infusions have been used in tests to treat moderate to severe inflammatory bowel disease, like Crohn's disease (CD) or ulcerative colitis (UC). These tests have shown some good results, but more research is needed to study their safety and effectiveness. Researchers want to see how well BMSC infusions work to treat CD and UC. The BMSCs will be collected from volunteer donors.
- To look at the safety and effectiveness of BMSC infusions for moderate to severe CD and UC.
- Individuals between 18 and 65 years old with moderate or severe inflammatory bowel disease (CD or UC) that has not responded to standard treatment.
- Participants will have two screening visits. The first will be 15 to 30 days before the first BMSC infusion. The second will be within 14 days of the first BMSC infusion.
- At the first screening visit, participants will have a physical exam and medical history. They will provide blood, urine, and stool samples. They will also give information about their symptoms and quality of life.
- At the second screening visit, participants will have their vital signs (like blood pressure and heart rate) measured. They will also provide blood samples, and have a colonoscopy with biopsies.
- During treatment, participants will have one BMSC infusion per week for 4 weeks. Blood and urine samples will be collected at each treatment visit.
- One week after the last infusion, participants will have a study visit. The tests from the first and second screening visits will be repeated.
- There will be six follow-up visits at 1, 2, 3, 6, 12, and 24 months after the last study visit. Participants will repeat the tests from the first screening visit.
|Inflammatory Bowel Disease||Other: Bone Marrow Stromal Cell (BMSC) Infusion||Phase 1|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||An Open-Label, Phase 1 Study to Assess the Safety and Tolerability of Bone Marrow Stromal Cell Infusion for the Treatment of Moderate to Severe Inflammatory Bowel Disease|
- Safety and tolerability, as measured by the presence of any AEs [ Time Frame: Day 0 through Week 16 ]
- Proportion of subjects who achieve clinical response and remission, mucosal healing, change in immunologic parameters and stability of remission/response at 3 months [ Time Frame: 3 months ]
|Study Start Date:||January 27, 2013|
|Estimated Study Completion Date:||November 1, 2019|
|Estimated Primary Completion Date:||November 1, 2017 (Final data collection date for primary outcome measure)|
All patients will receive the same treatment
Other: Bone Marrow Stromal Cell (BMSC) Infusion
Subjects will receive 4 weekly BMSC infusions and be monitored for AEs as well as for clinical improvement and mucosal healing.
Crohn s disease (CD) and ulcerative colitis (UC), the 2 major sub-types of inflammatory bowel disease (IBD), are chronic, life-long conditions characterized by relapsing inflammation of the gastrointestinal tract. CD has a predilection for the small bowel and the proximal large bowel; however, it can affect the gastrointestinal tract discontinuously anywhere. UC mainly affects the distal colon but can involve the entire colon as well. In spite of advances in IBD therapeutics, a significant number of patients continue to have symptoms while on conventional medications. The current protocol proposes to study infusions of allogenic bone marrow stromal cells (BMSCs) for the treatment of active IBD.
The purpose of this study is to evaluate the safety of BMSC infusions in subjects with IBD and to examine the host clinical and immunologic response to BMSCs. BMSCs possess multi-lineage differentiation potential in bone marrow, and aid in the repair of damaged tissue. They suppress the lymphocyte immune response and target sites of inflammation to promote healing through tissue regeneration. Studies are underway examining the utility of BMSCs to treat several conditions including neurologic disorders, myocardial infarctions, rheumatologic disorders, and gastrointestinal disorders including acute graft-versus-host-disease and IBD. Progress in the understanding of the cell populations involved in the pathogenesis of IBD and the discovery of the potential immunologic and regenerative characteristics of BMSCs have created a new potential direction for IBD therapy.
This phase I study will enroll subjects with moderate-to-severe IBD who are refractory to or intolerant of standard therapy. Under the guidance of the NIH Bone Marrow Stromal Cell Transplantation Center, the Cell Processing Section of the Department of Transfusion Medicine at the Clinical Center has developed a procedure for collecting, expanding, and cryopreserving clinical grade BMSCs under an FDA Drug Master File. Marrow will be aspirated from volunteer donors participating on protocol 10-CC-0053 who have passed the standard screening for blood and marrow donors; BMSCs will be expanded in vitro. Since it is not necessary to HLA-match BMSC donors with their recipients, a BMSC repository will be used as the source of BMSCs for this study.
In Arm 1, the safety of the BMSC infusion dosage (4 x 106 cells/kg/dose 10%) and schedule (once a week for 4 weeks) will be evaluated in 3 non-overlapping IBD subjects. Once safety is established in these subjects, subsequent subjects in Arm 2 will be enrolled without overlap restriction. Subjects will return to the clinic for safety and response assessments at 28, 56, 84, and 112 days after the first infusion. Additional safety visits will be performed at 180, 360 and 720 days after the first infusion. Safety will be monitored by a Data and Safety Monitoring Board. Response to study drug will be assessed in all patients by changes in symptom scores, endoscopic/histologic findings, quality of life scores, and immunologic/laboratory parameters. Fifty subjects will be evaluated over a 5-year period.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01851343
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Ivan J Fuss, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|