A new treatment for skin ulcers associated with systemic sclerosis using the ability of own bone marrow cells to regenerate blood vessels

JRCT ID: jRCTb032210204

Registered date:19/07/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Systemic sclerosis
• Date of first enrollment: 19/07/2021
• Target sample size: 12
• Countries of recruitment: Japan
• Study type: Interventional
• Intervention(s): Autologous bone marrow cell collection is performed by physicians using the same method as bone marrow transplantation performed in hematology. About 10 to 15 mL/kg body weight of bone marrow fluid is collected from both iliac bones under general anesthesia, and bone fragments and the like are removed using a bone marrow collection kit. Thereafter, bone marrow-derived mononuclear cells are separated and concentrated to about 40 to 100 mL by using a blood component separator. The physicians dispense 0.5 to 1.0 mL of the cell solution into 100 syringes in advance. A total of 40 to 100 mL of bone marrow mononuclear cells are transplanted equally to each of 200 limb skeletal muscles with a 22 to 27 G needle at 0.2 to 0.5 mL each. The total dose should be between 40 and 100 mL. If the number of bone marrow-derived mononuclear cells obtained by autologous bone marrow cell collection is less than the prescribed value, the physicians will determine the priority in the extremities according to the severity of skin ulcer and transplant to the three limbs, two limbs, or one limb. Gauze is applied to the transplanted limb after sterilization, and an elastic bandage is applied to the limbs. The gauze and elastic bandage will be released the day after the operation.

Outcome(s)

• Primary Outcome: Effective treatment rate

Secondary Outcome

(1) Number of skin ulcers
(2) Number of new skin ulcers
(3) The change rate of skin ulcer area
(4) Presence of cyanose
(5) The severity of Raynaud's phenomenon by Raynaud's Condition Score
(6) Pain evaluation by the visual analog scale
(7) Impairment assessment by health assessment questionnaire
(8) Amputation of the affected limb and the period until amputation
(9) Overall survival time

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 80age old
• Gender: Both

Include criteria

Include patients who meet all of the selection criteria (1) to (8).
(1) Patients with a total of 9 or more ACR/EULAR systemic sclerosis criteria at the time of diagnosis, and who have been clinically diagnosed with systemic sclerosis by a physician.
(2) Patients who are at least 20 years old and under 80 years old at the time of obtaining written consent (irrespective of gender).
(3) Patients who have intractable skin ulcers associated with systemic sclerosis and whose ulcer area reduction rate is less than 20% during the 12-week observation period before registration.
(4) Patients who are judged to be inadequately effective after treatment for the past 12 weeks or more with a standard treatment approved by the public health insurance for skin ulcers associated with systemic sclerosis.
(5) Patients who have not performed split-thickness skin grafting or limb amputation for skin ulcer/gangrene.
(6) Patients holding limbs.
(7) Patients who have not been treated with therapeutic angiogenesis similar to this study.
(8) Patients who have given written informed consent to participate in the study.

Exclude criteria

Subjects who do any of the following must not be included:
(1) Life expectancy is less than one year due to other complications.
(2) When there is a malignant tumor that has not been determined to be cured.
(3) If there is ischemic heart disease and blood circulation has not been reconstructed.
(4) If the HbA1c (NGSP) value within 10 days before registration is 10% or more, or if there is diabetic retinopathy.
(5) If there is an infection requiring systemic treatment or have a fever of 38.0 degrees C or more at the time of registration.
(6) If the laboratory test within 28 days before registration falls under the following or is a dialysis patient. a) AST: 100 U/L or more, b) ALT: 100 U/L or more, or c) eGFR: less than 25 mL/min/1.73m2.
(7) When there are severe blood diseases such as leukopenia and thrombocytopenia and severe anemia requiring blood transfusion.
(8) If patients are pregnant, nursing, may be pregnant or wish to become pregnant.
(9) Participation in clinical trials or clinical trials of drugs or medical devices within 28 days before registration in this study, and undergoing intervention such as test drugs.
(10) If there are other severe acute or chronic medical or mental conditions or abnormal laboratory values that may increase the risk of participating in the study or affect the interpretation of the study results.
(11) Patients who cannot escape amputation of the affected limb regardless of the success or failure of this treatment due to evidence of osteonecrosis or bone/tendon exposure in the ulcer/necrotic lesion before registration.
(12) Besides, when the chief investigator or the investigator judges that participation in this study is inappropriate.

Related Information

• Primary Sponsor: Yoshimi Ryusuke
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development