Trial record 1 of 1 for:    NCT01851343
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Bone Marrow Stromal Cells for Inflammatory Bowel Diseases

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier:
NCT01851343
First received: May 8, 2013
Last updated: July 18, 2014
Last verified: September 2013
  Purpose

Background:

- 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.

Objectives:

- To look at the safety and effectiveness of BMSC infusions for moderate to severe CD and UC.

Eligibility:

- Individuals between 18 and 65 years old with moderate or severe inflammatory bowel disease (CD or UC) that has not responded to standard treatment.

Design:

  • 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.

Condition Intervention Phase
Crohns
Ulcerative Colitis
Procedure: Allogenic Bone Marrow Stromal Cell Inf
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Safety and tolerability, as measured by the presence of any adverse events. [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: January 2013
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: Allogenic Bone Marrow Stromal Cell Inf
    N/A
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • ISUBJECT INCLUSION CRITERIA:

Subjects who meet ALL of the following criteria will be considered for enrollment into this study:

  1. Be 18 to 65 years of age, inclusive, as of the date of enrollment.
  2. Females of childbearing potential must agree not to become pregnant beginning from enrollment in the study to at least 12 weeks after the last BMSC infusion. Subjects must remain abstinent or use 2 methods of birth control to be selected from the following list:

    1. Hormonal methods.
    2. Surgical sterilization of either partner.
    3. Intrauterine device.
    4. Male or female condoms with a spermicide.
    5. Diaphragm, cervical cap, or sponge.
  3. Have a diagnosis of CD or UC that has been endoscopically or radiographically confirmed at least 6 months prior to screening.
  4. Have either active CD symptoms as defined by a CDAI score between 220 and 450, inclusive, as measured for 7 consecutive days during screening, or active UC as defined by a SCCAI score greater than or equal to 6.
  5. The patient must have demonstrated an inadequate response to, loss of response to, or intolerance of at least 1 of the following agents as defined below:

    • Corticosteroids

      • Signs and symptoms of persistently active disease despite a history of at least one 4-week induction regimen that included a dose equivalent to prednisone 30 mg daily orally for 2 weeks or intravenously for 1 week OR
      • Two failed attempts to taper corticosteroids to below a dose equivalent to prednisone 10 mg daily orally on 2 separate occasions OR
      • History of intolerance of corticosteroids (including, but not limited to Cushing s syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, infection)
    • Immunomodulators

      • Signs and symptoms of persistently active disease despite a history of at least one 8 week regimen of oral azathioprine (greater than or equal to 1.5 mg/kg) or 6-mercaptopurine mg/kg (greater than or equal to 0.75 mg/kg) OR
      • Signs and symptoms of persistently active disease despite a history of at least one 8 week regimen of methotrexate (greater than or equal to 12.5 mg/week) OR
      • History of intolerance of at least one immunomodulator (including, but not limited to nausea/vomiting, abdominal pain, pancreatitis, LFT abnormalities, lymphopenia, TPMT genetic mutation, infection)
    • TNF antagonists

      • Signs and symptoms of persistently active disease despite a history of at least one 4 week induction regimen of 1 of the following agents

        • Infliximab: 5 mg/kg IV, 2 doses at least 2 weeks apart
        • Adalimumab: one 80 mg SC dose followed by one 40 mg dose at least 2 weeks apart
        • Certolizumab pegol: 400 mg SC, 2 doses at least 2 weeks apart OR
      • Recurrence of symptoms during scheduled maintenance dosing following prior clinical benefit (discontinuation despite clinical benefit does not qualify) OR
      • History of intolerance of at least 1 TNF antagonist (including, but not limited to infusion-related reaction, demyelination, congestive heart failure, infection)
  6. May be receiving a therapeutic dose of the following drugs:

    • Oral 5-ASA compounds provided that the dose has been stable for the 2 weeks immediately prior to enrollment
    • Oral corticosteroid therapy (prednisone at a stable dose less than or equal to 30 mg/day, budesonide at a stable dose less than or equal to 9 mg/day, or equivalent steroid) provided that the dose has been stable for the 4 weeks immediately prior to enrollment if corticosteroids have just been initiated, or for the 2 weeks immediately prior to enrollment if corticosteroids are being tapered
    • Probiotics (e.g., Culturelle, Saccharomyces boulardii) provided that the dose has been stable for the 2 weeks immediately prior to enrollment
    • Antidiarrheals (e.g., loperamide, diphenoxylate with atropine) for control of chronic diarrhea
    • Azathioprine or 6-mercaptopurine provided that the dose has been stable for the 8 weeks immediately prior to enrollment
    • Methotrexate provided that the dose has been stable for the 8 weeks immediately prior to enrollment
    • Antibiotics used for the treatment of CD (i.e., ciprofloxacin, metronidazole) provided that the dose has been stable for the 2 weeks immediately prior to enrollment
  7. Subjects must agree to have samples of their blood and tissue samples stored for potential future research use.
  8. Subjects must have a primary medical care provider.

SUBJECT EXCLUSION CRITERIA

Subjects who meet ANY of the following criteria will be excluded from participation in this study:

  1. Subjects who are currently taking greater than or equal to 20 mg of prednisone per day. Subjects on corticosteroids must be on a stable dose for at least 4 weeks.
  2. Concomitant treatment with anti-TNF therapy (or other biological therapy). The following washout period will be required for subjects to be eligible to participate in the trial:

    1. Three months washout prior to baseline for certolizumab or natalizumab.
    2. Two months washout prior to baseline for adalimumab, etanercept, and infliximab.
    3. One month washout prior to baseline for cyclosporine, mycophenolate,

    pimecrolimus, tacrolimus, and any other systemic immunosuppressants.

  3. Pregnant or breastfeeding. Serum pregnancy test must be negative at screening for

    female subjects of childbearing potential. Urine pregnancy test must remain negative

    at each of the four infusion visits.

  4. Has clinically significant systemic infection (e.g., chronic or acute infection, urinary tract infection, upper respiratory tract infection) within three months of screening and no opportunistic infection within six months of screening. Has a history or presence of recurrent or chronic infection (e.g. viral infections [including hepatitis B or C, HIV], bacterial infections, systemic fungal infections, or syphilis).
  5. Has a positive Quantiferon-TB Gold (QFT-G) test, indicating tuberculosis infection, at time of screening. A QFT-G will not be done in a subject who has received tuberculosis vaccination; these subjects will be eligible to participate if latent tuberculosis can be excluded with a chest x-ray (CXR).
  6. Received an agent not approved by the FDA for marketed use in any indication or any small molecule inhibitors (e.g., Naltrexone) within 90 days of beginning the screening CDAI diary or at any time during the screening window. This includes medications used to treat IBD as an off-label use (at the discretion of the investigator).
  7. Has abnormal hematological and biochemical parameters, including:

    1. Neutrophil count < 1500 cells/mm(3).
    2. Hemoglobin < 9 g/dL.
    3. Platelet count less than or equal to150,000 cells/mm(3).
    4. Creatinine greater than or equal to1.2 times the upper limit of normal (ULN).
    5. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) greater than or equal to2 times ULN.
    6. Prothrombin time-International Normalized Ratio (PT-INR) > 2 and/or on chronic anticoagulation medications.
    7. If total bilirubin is greater than 1.2 mg/dL, then direct bilirubin can be no more than 70% of the total, up to a direct bilirubin of 2.0 mg/dL.
  8. Has active infection with enteric pathogens as evidenced by positive microbiological culture of stool.
  9. Has active cytomegalovirus (CMV) infection. CMV polymerase chain reaction (PCR) testing will be performed on biopsies taken during the time of initial colonoscopy in order to exclude CMV.
  10. Has a history of low-grade or high-grade colonic mucosal dysplasia.
  11. Has a history of uveitis or iritis within the previous two months. This is due to the concern that BMSCs may home to sites of active inflammation.
  12. Had bowel surgery other than perianal (e.g., fistulotomy, seton placement, abscess drainage) within 6 months prior to beginning the CDAI screening diary or drawing screening blood samples.
  13. Has surgical changes to gut anatomy that preclude administration of clinical activity indicies including but not limited to ileostomy, colostomy, or subtotal colectomy with ileorectal anastomosis.
  14. Has known or suspected short bowel syndrome.
  15. Requires parenteral or total parenteral nutrition.
  16. Has a history of cancer, other than non-melanomatous cancer of the skin, within the past 5 years.
  17. Unwillingness or inability to comply with study requirements.
  18. Has any medical or psychiatric condition that, in the opinion of the investigator, contraindicates participation in this protocol.
  19. Has only small bowel IBD that is inaccessible by standard colonoscopy to obtain research biopsies. For this reason patients with only upper gastrointestinal IBD are also excluded.
  20. Refuses to abstain from using COX-2 inhibitors or NSAIDs throughout the 4 week study drug infusion period.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01851343

Contacts
Contact: Kimberly L Montgomery-Recht, R.N. (301) 827-0038 kim.montgomery-recht@nih.gov
Contact: Ivan J Fuss, M.D. (301) 496-9663 ifuss@niaid.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Ivan J Fuss, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier: NCT01851343     History of Changes
Other Study ID Numbers: 130077, 13-I-0077
Study First Received: May 8, 2013
Last Updated: July 18, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Stem Cell Infusion
Crohns
Ulcerative Colitis
Inflammation
Diarrhea

Additional relevant MeSH terms:
Colitis
Colitis, Ulcerative
Inflammatory Bowel Diseases
Intestinal Diseases
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on July 26, 2014