Bone Marrow Stromal Cells for Inflammatory Bowel Diseases

NCT01851343 | Terminated Phase 1

• 2 other identifiers: 13007713-I-0077
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Inflammatory Bowel Disease

Keywords

Stem Cell Infusion; Crohns; Ulcerative Colitis; Inflammation; Diarrhea

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability, as measured by the presence of any AEs

  Day 0 through Week 16

Secondary Outcomes (1)

• Proportion of subjects who achieve clinical response and remission, mucosal healing, change in immunologic parameters and stability of remission/response at 3 months

  3 months

Study Arms (1)

1

EXPERIMENTAL

All patients will receive the same treatment

Other: Bone Marrow Stromal Cell (BMSC) Infusion

Interventions

Bone Marrow Stromal Cell (BMSC) Infusion OTHER

Subjects will receive 4 weekly BMSC infusions and be monitored for AEs as well as for clinical improvement and mucosal healing.

1

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who meet ALL of the following criteria will be considered for enrollment into this study:
• Be 18 to 65 years of age, inclusive, as of the date of enrollment.
• Be willing to take appropriate measures to avoid pregnancy during the study period. Subject to the judgment and discretion of the PI, participants who meet ANY of the criteria listed immediately below, as well as male participants who are in a monogamous relationship with a woman who meets ANY of the criteria below, may not be required to take any pregnancy avoidance measures (e.g. barrier methods). Such participants will be counseled on risks at the time of consent and at appropriate points (e.g. when pregnancy testing occurs) during the study:
• Females who have had their uterus, and/or BOTH ovaries removed
• Females who have had BOTH fallopian tubes surgically tied or removed
• Females who have undergone other permanent birth control procedures, such as endometrial ablation or sterilization (such as Essure or Novasure), and have had any required follow up testing to confirm the effectiveness of the permanent birth control procedure.
• Females who are above the age of 50 and have spontaneously had no menses at any point during the past 12 or more consecutive months (i.e. have reached menopause).
• Females who, in the conservative and reasonable judgment of the PI (e.g. due to sexual orientation, or serious life choice), from the time of enrollment until
• weeks after the last BMSC infusion, will NOT participate in any potentially reproductive sexual contact (i.e. sexual intercourse with a male partner).
• Males who have had a vasectomy and have had the follow-up testing confirming zero sperm count in their semen.
• Any subject who does NOT meet the criteria listed in #2 above, will be appropriately counseled on reproductive risks and pregnancy avoidance, and will be required to adhere to the following measures, as agreed upon by the subject and the PI until at least 12 weeks after the last BMSC infusion:
• A highly effective hormonal method to prevent pregnancy \[e.g. CONSISTENT, CONTINUOUS use of contraceptive pill, patch, ring, implant or injection\], and/or IUD or equivalent.
• IN ADDITION TO
• A barrier method to be used at the time of potentially reproductive sexual activity (e.g. \[male/female condom, cap, or diaphragm\] + spermicide).
• Male participants will be appropriately counseled on risks and must agree to consistently use effective contraception with female sexual partners through the Day 112 study visit to avoid a pregnancy that could be affected by the study drug. Appropriate measures to avoid pregnancy and trial related risks in sexual partners, per the PI s judgment, must be agreed to and practiced.

You may not qualify if:

• Subjects who meet ANY of the following criteria will be excluded from participation in this study:
• 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.
• Concomitant treatment with anti-TNF therapy (or other biological therapy) or with Entyvio/vedolizumab. The following washout period will be required for subjects to be eligible to participate in the trial:
• Three months washout prior to baseline for certolizumab or natalizumab.
• Two months washout prior to baseline for adalimumab, etanercept, infliximab, and Entyvio/vedolizumab.
• One month washout prior to baseline for cyclosporine, mycophenolate,
• pimecrolimus, tacrolimus, and any other systemic immunosuppressants.
• 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.
• Subject does not agree to pregnancy avoidance measures required to prevent pregnancy during participation in the study, or meet criteria that would exempt them from contraceptive measures.
• Has clinically significant systemic infection (e.g., chronic or acute infection, urinary tract infection, upper respiratory tract infection) within one month 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).
• 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).
• 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).
• Has abnormal hematological and biochemical parameters, including:
• Neutrophil count \<1500 cells/mm(3).
• Hemoglobin \<9 g/dL.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Devine SM, Cobbs C, Jennings M, Bartholomew A, Hoffman R. Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates. Blood. 2003 Apr 15;101(8):2999-3001. doi: 10.1182/blood-2002-06-1830. Epub 2002 Dec 12.

  PMID: 12480709 BACKGROUND

• Nauta AJ, Fibbe WE. Immunomodulatory properties of mesenchymal stromal cells. Blood. 2007 Nov 15;110(10):3499-506. doi: 10.1182/blood-2007-02-069716. Epub 2007 Jul 30.

  PMID: 17664353 BACKGROUND

• Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999 Apr 2;284(5411):143-7. doi: 10.1126/science.284.5411.143.

  PMID: 10102814 BACKGROUND

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Colitis, Ulcerative; Inflammation; Diarrhea

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colonic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Digestive; Signs and Symptoms

Study Officials

• Ivan J Fuss, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2013
• First Posted: May 10, 2013
• Study Start: January 27, 2013
• Primary Completion: July 12, 2017
• Study Completion: July 12, 2017
• Last Updated: March 29, 2019

Record last verified: 2017-07-12

Locations

US (1)