Safety and Feasibility of Umbilical Cord Blood Cell Transplant Into Injured Spinal Cord

• ClinicalTrials.gov Identifier: NCT01046786
• Recruitment Status: Completed
• First Posted: January 12, 2010
• Last Update Posted: January 28, 2014
• Sponsor: China Spinal Cord Injury Network
• Collaborators: Chinese University of Hong Kong; The University of Hong Kong
• Information provided by (Responsible Party): China Spinal Cord Injury Network

Study Description

Brief Summary:

To investigate the feasibility, safety, efficacy and optimal dose of umbilical cord blood mononuclear cell transplant in the treatment of chronic spinal cord injuries.

Condition or disease	Intervention/treatment	Phase
Spinal Cord Injuries	Biological: Umbilical Cord Blood Mononuclear Cell; Drug: Methylprednisolone; Drug: Lithium	Phase 1; Phase 2

Detailed Description:

This is an open-label, dose-escalating clinical trial. Three groups of four patients will receive transplants of increasing doses of HLA-matched umbilical cord blood mononuclear cell into the spinal cord. In the fourth group, we will transplant the highest volume of cells that did not increase neurological deficits along with a single bolus of 30mg/kg methylprednisolone sodium succinate. In the fifth group of four subjects, we will inject that volume of cells plus a bolus intravenous dose of 30mg/kg methylprednisolone sodium succinate and a 6-week course of oral lithium carbonate titrated to 0.6-1.0 mM serum levels. All the subjects are encouraged to stand or walk for one hour a day after the cell transplantation.

The neurological and walking outcomes will be assessed 1, 2, 6, 24 and 48 weeks after transplantation. The outcomes of the five treatment groups will be compared by analysis of variance and, if possible, correlation with cell dose. Efficacy and safety will be analyzed comparing neurological change scores amongst the five different treatment groups. Loss of motor (>5 points) or sensor scores (>2 points) from baseline pre-treatment levels would be considered deleterious. Increases in scores above baseline would be considered beneficial.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Feasibility of Umbilical Cord Blood Cell Transplant Into Injured Spinal Cord: an Open-Labeled, Dose-Escalating Clinical Tiral
• Study Start Date: January 2010
• Actual Primary Completion Date: October 2013
• Actual Study Completion Date: December 2013

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Group A; Intraspinal injection of 1.6 million cord blood mononuclear cell	Biological: Umbilical Cord Blood Mononuclear Cell; The cord blood mononuclear cells are obtained from thawed units of HLA-matched human umbilical cord blood. The cells will be slowly injected into the posterior gray matter after laminectomy and opening of the dura.
Active Comparator: Group B; Intraspinal injection of 3.2 million cord blood mononuclear cell	Biological: Umbilical Cord Blood Mononuclear Cell; The cord blood mononuclear cells are obtained from thawed units of HLA-matched human umbilical cord blood. The cells will be slowly injected into the posterior gray matter after laminectomy and opening of the dura.
Active Comparator: Group C; Intraspinal injection of 6.4 million cord blood mononuclear cell	Biological: Umbilical Cord Blood Mononuclear Cell; The cord blood mononuclear cells are obtained from thawed units of HLA-matched human umbilical cord blood. The cells will be slowly injected into the posterior gray matter after laminectomy and opening of the dura.
Active Comparator: Group D; Intraspinal injection of 6.4 million cord blood mononuclear cell plus 30 mg/kg methylprednisolone	Biological: Umbilical Cord Blood Mononuclear Cell; The cord blood mononuclear cells are obtained from thawed units of HLA-matched human umbilical cord blood. The cells will be slowly injected into the posterior gray matter after laminectomy and opening of the dura.; Drug: Methylprednisolone; 30 mg/kg methylprednisolone
Active Comparator: Group E; Intraspinal injection of 6.4 million cord blood mononuclear cell plus 30 mg/kg methylprednisolone plus 6 week course of oral lithium, titrated to maintain 0.6-1.0 mM serum level	Biological: Umbilical Cord Blood Mononuclear Cell; The cord blood mononuclear cells are obtained from thawed units of HLA-matched human umbilical cord blood. The cells will be slowly injected into the posterior gray matter after laminectomy and opening of the dura.; Drug: Methylprednisolone; 30 mg/kg methylprednisolone; Drug: Lithium; oral lithium, titrated to maintain 0.6-1.0 mM serum level

Outcome Measures

Primary Outcome Measures :

1. ASIA motor scores and sensory scores [ Time Frame: 0, 1, 2, 6 24 and 48 weeks ]
2. ASIA Impairment Scale grade [ Time Frame: 0, 1, 2, 6 24 and 48 weeks ]

Secondary Outcome Measures :

1. MRI and Diffusion Tensor Imaging of spinal cord [ Time Frame: 0, 1, 24 and 48 weeks ]
2. Spinal Cord Independence Measure (SCIM) score [ Time Frame: 0, 6, 24 and 48 weeks ]
3. Walking Index of Spinal Cord Injury (WISCI) level [ Time Frame: 0, 6, 24 and 48 weeks ]
4. Modified Ashworth Scale (MAS) of Spasticity [ Time Frame: 0, 1, 2, 6, 24 and 48 weeks ]
5. Visual Analog Scale (VAS) of pain [ Time Frame: 0, 1, 2, 6, 24 and 48 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Subjects of either gender and 18-60 years old
• Subjects with chronic spinal cord injury (defined as ≧12 months post-initial SCI surgery) with stable neurological findings for at least 6 months
• Subject with a current neurological status of ASIA A
• The neurological level of the subjects is between C5 and T11
• The MRI shows that the injured site of the spinal cord is within three vertebral levels and there is no cyst
• Subjects must be able to read, understand, and complete the Visual Analog Scale
• Subjects who have voluntarily signed and dated an informed consent form, approved by the appropriate IRB, prior to any study-specific procedures

Exclusion Criteria:

• Significant renal, cardiovascular, hepatic and psychiatric diseases
• Significant medical diseases or infection (including but not limited to the carrier of hepatitis B virus or HIV)
• Pregnant or lactating woman
• Female of childbearing potential and who is unwilling to use an effective contraceptive method while enrolled in the study
• The MRI shows that the length of spinal cord lesion exceeds three segments or there is cyst in the spinal cord
• The lesion edge of the spinal cord cannot be determined by imaging technology
• Unavailability of HLA matched umbilical cord blood cells
• Any contraindication of laminectomy operation, MPSS and/or lithium carbonate
• Subject who is currently participating in another investigational study or has been taking any investigational drug within the last 4 weeks prior to screening of this study and finally
• Any criteria, which, in the opinion of the investigator, suggests that the subject would not be compliant with the study protocol and/or would not be suitable to participant this study

Contacts and Locations

Locations

Hong Kong

Queen Mary Hospital

Hong Kong, Hong Kong

Prince of Wales Hospital

Shatin, Hong Kong

Sponsors and Collaborators

China Spinal Cord Injury Network

Chinese University of Hong Kong

The University of Hong Kong

Investigators

• Principal Investigator: Wai Sang Poon, MD; The Chinese University of Hong Kong / Prince of Wales Hospital
• Principal Investigator: Gilberto Leung, MD; The University of Hong Kong / Queen Mary Hospital

More Information

• Responsible Party: China Spinal Cord Injury Network
• ClinicalTrials.gov Identifier: NCT01046786
• Other Study ID Numbers: CN102B
• First Posted: January 12, 2010
• Last Update Posted: January 28, 2014
• Last Verified: January 2014

Keywords provided by China Spinal Cord Injury Network:

spinal cord injury; cord blood mononuclear cell; Methylprednisolone; Lithium Carbonate

Additional relevant MeSH terms:

Spinal Cord Injuries; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuroprotective Agents; Protective Agents; Antineoplastic Agents, Hormonal; Antineoplastic Agents