Clinical Research on Treatment of Psoriasis by Human Umbilical Cord-derived Mesenchymal Stem Cells

• ClinicalTrials.gov Identifier: NCT03765957
• Recruitment Status: Not yet recruiting
• First Posted: December 5, 2018
• Last Update Posted: December 5, 2018
• Sponsor: Central South University
• Information provided by (Responsible Party): Yijing He, Central South University

Study Description

Brief Summary:

To evaluate the effect and safety of treatment of psoriasis by human umbilical cord blood-derived mesenchymal stem cell

Condition or disease	Intervention/treatment	Phase
Psoriasis	Biological: Mesenchymal Stem Cells; Drug: Oral Methotrexate	Early Phase 1

Detailed Description:

Psoriasis is a chronic and recurrent inflammatory skin disease and its histological features are characterized by epidermal hyperplasia, increased angiogenesis and immune cell infiltration. Psoriasis prevalence is about 0.1%-3%, affecting approximately 125 million people worldwide. In China, there are about 10 million psoriasis patients.

Human umbilical cord blood-derived MSC (hUCB-MSC) has many advantages for the treatment of immune disease. Because it was demonstrated that hUCB-MSCs are effective in modulating immune cells and treating diseases and it has low immunogenicity. Furthermore, hUCB-MSCs do not raise ethical issue for clinical applications.

Some experimental results and cases has showed that mesenchymal stem cell (MSC) can prevent or treat psoriasis. This clinical study is conducted to provide more data to evaluate the effect and safety of treatment of psoriasis by human umbilical cord blood-derived mesenchymal stem cell.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical Research on Treatment of Psoriasis by Human Umbilical Cord-derived Mesenchymal Stem Cells
• Estimated Study Start Date: January 1, 2019
• Estimated Primary Completion Date: July 31, 2020
• Estimated Study Completion Date: June 1, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Mesenchymal Stem Cells; The mesenchymal stem cells will be derived from human umbilical cord. The subjects will be injected intravenously with 1x10E6/kg （according to the weight of subject）mesenchymal stem cells at baseline and every 2 weeks until week 6.	Biological: Mesenchymal Stem Cells; The subjects will be injected intravenously with 1x10E6/kg （according to the weight of subject）Human Umbilical Cord-derived Mesenchymal Stem Cells at baseline and every 2 weeks until week 6. Besides MSC, conventional moisturizer such 10% boric acid ointment is given to all patients in the treatment and follow-up period.; Other Name: Human Umbilical Cord-derived Mesenchymal Stem Cells
Active Comparator: Oral Methotrexate; The subjects will be treated with oral methotrexate 7.5-15mg every week (The dose will start from 7.5mg/w and increase to 15mg/w depending on the response of subjects). This is a conventional systemic treatment.	Drug: Oral Methotrexate; The subjects will be treated with oral methotrexate 7.5-15mg every week (The dose will start from 7.5mg/w and increase to 15mg/w depending on the response of subjects). Besides methotrexate, conventional moisturizer such 10% boric acid ointment is given to all patients in the treatment and follow-up period.; Other Name: MTX

Outcome Measures

Primary Outcome Measures :

1. Number of Participants Achieving Psoriasis Area and Severity Index ≥75% (PASI 75) Improvement [ Time Frame: Month 6 ]
   The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation (scaling), erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Participants achieving PASI 75 was defined as having an improvement of at least 75% in the PASI scores compared to baseline.
2. Number of Participants Achieving a Static Physician Global Assessment (sPGA) of (0, 1) [ Time Frame: Month 6 ]
   The sPGA is a physician's determination of the participant's psoriasis lesions overall at a given time point categorized by descriptions for induration, erythema, and scaling. For the analysis of responses, the participant's psoriasis is assessed as clear (0), minimal (1), mild (2), moderate (3), severe (4), or very severe (5). An sPGA (0,1) response was defined as a post-baseline sPGA score of 0 or 1.

Secondary Outcome Measures :

1. Number of Participants Achieving an sPGA (0) [ Time Frame: Month 6 ]
   The sPGA is a physician's determination of the participant's psoriasis lesions overall at a given time point categorized by descriptions for induration, erythema, and scaling. For the analysis of responses, the participant's psoriasis is assessed as clear (0), minimal (1), mild (2), moderate (3), severe (4), or very severe (5). An sPGA (0) response was defined as a post-baseline sPGA score of 0.
2. Number of Participants Achieving ≥90% (PASI 90) Improvement [ Time Frame: Month 6 ]
   The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation (scaling), erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Participants achieving PASI 90 were defined as having an improvement of at least 90% in the PASI scores compared to baseline.
3. Number of Participants Achieving 100% [ Time Frame: Month 6 ]
   The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation (scaling), erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Participants achieving PASI 100 were defined as having an improvement of at least 100% in the PASI scores compared to baseline.
4. Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score [ Time Frame: Baseline, Month 6 ]
   The DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include "not at all," "a lot," and "very much," with corresponding scores of 1, 2, and 3, respectively, and unanswered ("not relevant") responses scored as "0." Totals range from 0 to 30 (less to more impairment), and a 5 point change from baseline is considered clinically relevant. Least Square (LS) Means in total DLQI score were calculated using Mixed Model Repeated Measures (MMRM) with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Diagnosed according to Classification criteria for Psoriasis vulgaris for more than 6 months;
2. Body Mass Index (BMI) between 18.5-35;
3. Resistance to phototherapy, systemic therapy, or a combination of these therapies
4. BSA(body surface area)>10%, sPGA>3 and PASI>10 at baseline;
5. Understanding the whole process of the study, voluntary participation and signed the informed consent.

Exclusion Criteria:

1. WBC(white blood cell count ) <3.0x109/L, blood platelet count<100x109/L, hemoglobin<100g/L serum creatinine>1.5 x ULN(upper limit of normal), bilirubin > 1.5 x ULN(upper limit of normal), AST(SGOT,glutamic-oxalacetic transaminase)/ALT(SGPT,glutamic-pyruvic transaminase) >2.5 x ULN(upper limit of normal);
2. Pregnant women, or women who ready for pregnancy or lactating;
3. Have a serious heart, lung, kidney and other vital organs and endocrine system lesions and the history;
4. Patients suffering from malignant tumor;
5. Patients suffering from any acute or chronic infectious diseases;
6. Mental disorders, history of alcohol abuse, drug or other substance abuse;
7. Patients participated in any clinical trials within 3 months or any stem cell therapy within 6 months;
8. Having a serious allergic history or being allergic to two or more than 2 kinds of food or drugs;
9. Patients who have received systemic therapy within recent one month or topical therapy in two weeks;
10. Either HIV-antibody(human immunodeficiency virus-antibody), HBV-antibody (hepatitis B virus-antibody ) or syphilis antibody is positive;
11. Other cases which researchers believe that can not enroll.

Contacts and Locations

Contacts

Contact: Mi Zhang; 08615116331788 ext 08615116331788; 648979182@qq.com

Sponsors and Collaborators

Central South University

More Information

Publications:

Comella K, Parlo M, Daly R, Dominessy K. First-in-man intravenous implantation of stromal vascular fraction in psoriasis: a case study. Int Med Case Rep J. 2018 Mar 21;11:59-64. doi: 10.2147/IMCRJ.S163612. eCollection 2018.

Lee YS, Sah SK, Lee JH, Seo KW, Kang KS, Kim TY. Human umbilical cord blood-derived mesenchymal stem cells ameliorate psoriasis-like skin inflammation in mice. Biochem Biophys Rep. 2016 Oct 8;9:281-288. doi: 10.1016/j.bbrep.2016.10.002. eCollection 2017 Mar.

Boehncke WH, Schön MP. Psoriasis. Lancet. 2015 Sep 5;386(9997):983-94. doi: 10.1016/S0140-6736(14)61909-7. Epub 2015 May 27. Review.

Owczarczyk-Saczonek A, Krajewska-Włodarczyk M, Kruszewska A, Placek W, Maksymowicz W, Wojtkiewicz J. Stem Cells as Potential Candidates for Psoriasis Cell-Replacement Therapy. Int J Mol Sci. 2017 Oct 20;18(10). pii: E2182. doi: 10.3390/ijms18102182. Review.

Guan LX, Guan H, Li HB, Ren CA, Liu L, Chu JJ, Dai LJ. Therapeutic efficacy of umbilical cord-derived mesenchymal stem cells in patients with type 2 diabetes. Exp Ther Med. 2015 May;9(5):1623-1630. Epub 2015 Mar 9.

Ra JC, Kang SK, Shin IS, Park HG, Joo SA, Kim JG, Kang BC, Lee YS, Nakama K, Piao M, Sohl B, Kurtz A. Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells. J Transl Med. 2011 Oct 21;9:181. doi: 10.1186/1479-5876-9-181.

Dahbour S, Jamali F, Alhattab D, Al-Radaideh A, Ababneh O, Al-Ryalat N, Al-Bdour M, Hourani B, Msallam M, Rasheed M, Huneiti A, Bahou Y, Tarawneh E, Awidi A. Mesenchymal stem cells and conditioned media in the treatment of multiple sclerosis patients: Clinical, ophthalmological and radiological assessments of safety and efficacy. CNS Neurosci Ther. 2017 Nov;23(11):866-874. doi: 10.1111/cns.12759. Epub 2017 Sep 29.

Cui GH, Wang YY, Li CJ, Shi CH, Wang WS. Efficacy of mesenchymal stem cells in treating patients with osteoarthritis of the knee: A meta-analysis. Exp Ther Med. 2016 Nov;12(5):3390-3400. Epub 2016 Oct 11.

• Responsible Party: Yijing He, Associate professor, Central South University
• ClinicalTrials.gov Identifier: NCT03765957 History of Changes
• Other Study ID Numbers: 2018-MSC/CSU/PS
• First Posted: December 5, 2018
• Last Update Posted: December 5, 2018
• Last Verified: December 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Yijing He, Central South University:

Mesenchymal Stem Cells

Additional relevant MeSH terms:

Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Methotrexate; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Dermatologic Agents; Enzyme Inhibitors; Folic Acid Antagonists; Immunosuppressive Agents; Immunologic Factors; Antirheumatic Agents; Nucleic Acid Synthesis Inhibitors