Mesenchymal Cell Therapy in Osteogenesis Imperfecta (OI)

This is a Phase 1/2 study to determine the safety and efficacy of allogeneic (third party), bone-marrow derived mesenchymal stromal cells (MSCs) for the treatment of Osteogenesis Imperfecta (OI) Type 3. It will evaluate this by looking at whether there are treatment related infusion reactions, and assessing linear growth rates and bone health, both of which are impaired in patients ages 3-10 with Osteogenesis Imperfecta Type 3. This is a single-site non-randomized clinical trial, that will take place at Children's Healthcare of Atlanta (CHOA) at Egleston and Emory Children's Center.

This is a Phase 1/2 study to determine the safety and efficacy of allogeneic (third party), bone-marrow derived mesenchymal stromal cells (MSCs) for the treatment of Osteogenesis Imperfecta (OI) Type 3. It will evaluate this by looking at whether there are treatment related infusion reactions, and assessing linear growth rates and bone health, both of which are impaired in patients ages 3-10 with Osteogenesis Imperfecta Type 3. This is a single-site non-randomized clinical trial, that will take place at Children's Healthcare of Atlanta (CHOA) at Egleston and Emory Children's Center. MSCs will be infused through IV every 4 months for 6 total infusions. There will be a baseline visit before MSC therapy is initiated, and there will be a follow up visits every 4 months for 1 year after the final MSC infusion. These infusions will take place in between pamidronate infusions (i.e. 2 months after the last pamidronate infusion, and 2 months before the next one). Pamidronate aids in treatment of bone pain and bone mineral density but does not correct the underlying defect nor does it show substantial improvements in linear growth. After the MSC infusions, patients will be provided an overnight at Ronald McDonald House, or a hospital affiliated hotel so they can be near to the hospital in case of any unanticipated effects, and for a follow up visit the next morning. Labs will be collected during every visit to look at bone metabolism. Limb and bone age x-rays, pQCT scans, and dual-energy x-ray absorptiometry (DXA) scans will be completed annually, while spine films will be completed every 18 months. These images will directly examine bone health. Body measurements will be taken every visit as well to assess linear growth. The patients' parents will complete events diaries and submit them each infusion day to evaluate fractures that occurred between visits. Patients and their parents will also complete quality of life surveys once a year. There will be financial compensation for each study visit. Subjects will also be provided a free lunch on days when radiology visits occur and will be reimbursed for parking. Subjects will be identified and recruited mainly through Children's endocrinology clinic. There will also be advertisements to the OI foundation, and neighboring pediatric hospitals with OI programs such as University of Alabama at Birmingham, and Vanderbilt. If identified as eligible to participate, the study team will seek approval by the subjects' primary endocrinologist. The consent process will then take place in person during a baseline visit. There is an optional part of the study that involves donation of a bone fragment that is taken out during a routine surgical rodding procedure. This piece of bone is removed and discarded, if it is not donated, making it minimal risk. Bone sample donation will be available to OI Type 3 subjects receiving MSCs, and to OI Type 3 subjects who are not receiving MSCs but want to participate in research. Leftover blood samples, and bone fragments may be stored for future research by the sponsor of this study. The purpose of this study is to help doctors and scientists learn if serial MSC infusions will safely and effectively aid in growth, bone health, and ultimately improve motoric function and quality of life in this population.