Mesenchymal Stem Cell Transfusion for the Treatment of Refractory Lupus Nephritis

NCT06485648 | Not Yet Recruiting Early Phase 1

• 2 other identifiers: 2023-5332020YFA0113004
• Study Type: interventional
• Target: 96
• Locations: 0 countries
• Sites: N/A

Brief Summary

Lupus nephritis (LN) is the most common and serious complication of systemic lupus erythematosus (SLE), which can lead to permanent kidney injury and uremia. At present, the combination of glucocorticoids and immunosuppressants is still the first line of clinical treatments. Only about 20%-30% of patients with LN can achieve a complete response. In addition, attainment of clinical remission does not necessarily reflect improvement in the kidney tissues, A substantial proportion of patients who show a clinical response to treatment still have histological findings in their kidney biopsy samples that are consistent with active kidney disease after clinical complete remission. Because of the complexity of refractory lupus nephritis, there is no uniform and effective treatment for them. Mesenchymal stem cells (MSCs) are a class of pluripotent stem cells, that can secrete hundreds of cytokines to participate in immune regulation, anti-inflammatory and anti-fibrosis processes, etc., so they have been actively explored for the treatment of autoimmune diseases which Including systemic lupus erythematosus and lupus nephritis recently. Therefore, MSCs have been considered as a potential therapeutic regimen for the treatment of refractory LN. Several clinical trials have been performed, but the results have been inconsistent and the outcome indicators of treatment were not verified by pathological findings. Therefore, this trial wishes to investigate whether MSCs can improve renal recovery in patients with refractory lupus nephritis and to evaluate the effectiveness of treatment by renal biopsy.

Conditions

Lupus Nephritis

Keywords

lupus nephritis; Mesenchymal Stem Cells; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (3)

• Complete response rate

  * Number of participants with reduction in content of Protein creatinine ratio \<0.5 g/g (50 mg/mmol) measured as the from of 24h-urine collection * Stabilization or improvement in kidney function (±10%-15% of baseline) * Within 6-12 month of starting therapy, but could take more than 12 month

  Within 6-12 mo of starting therapy, but could take more than 12 mo

• Partial response rate

  * Number of participants with reduction in content of Protein creatinine ratio by at least 50% and to \<3 g/g (300 mg/mmol) measured from a 24-h urine collection * Stabilization or improvement in kidney function (±10%-15% of baseline) * Within 6-12 mo of starting therapy

  Within 6-12 mo of starting therapy

• No kidney response rate

  • Number of participants with failure to achieve a partial or complete response within 6-12 mo of starting therapy

  within 6-12 mo of starting therapy

Secondary Outcomes (4)

• Number of participants with varying degrees of LN activity according to SLEDAI 2000 and BILAG 2004.

  within 6-12 mo of starting therapy

• Number of participants with the recurrence within 48 weeks after complete and partial remission.

  within 6-12 mo of starting therapy

• Number of participants with abnormal laboratory tests results for blood routine; blood biochemistry; urine routine; Immune indexes (ANA, Anti-dsDNA, C1q, C3, C4, etc.) and umor markers.

  within 6-12 mo of starting therapy

• Overall survival rate and survival rate without renal involvement.

  within 6-12 mo of starting therapy

Study Arms (2)

Control

PLACEBO COMPARATOR

Drug: Normal saline

Treatment

EXPERIMENTAL

Biological: Umbilical cord mesenchymal stem cells

Interventions

Umbilical cord mesenchymal stem cells BIOLOGICAL

Treatment: G(glucocorticoid) + i.v. uc-MSC (1×106 cells/Kg)

Treatment

Normal saline DRUG

Control: G(glucocorticoid) + i.v. Normal saline

Control

Eligibility Criteria

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

You may qualify if:

• years old (including 18 and 65 years old, gender is not limited);
• According to the revised criteria of ACR, the diagnosis of SLE was confirmed;
• Diagnosed with LN (III, IV or III+V or IV+V) active lesions according to the 2016 revised ISN/RPS renal pathological classification criteria and unachieved a partial or complete response within 6-12 month of starting standard therapy.

You may not qualify if:

• Do not agree to sign the informed consent;
• Pregnancy, lactation or do not agree to take effective contraceptive measures during the trial and within 12 months after the trial;
• Kidney biopsy indicated chronic nephritis (extensive glomerular sclerosis, extensive fibrous crescent formation, extensive interstitial fibrosis, tubule atrophy);
• In addition to SLE, patients with other autoimmune diseases (dermatomyositis/polymyositis, mixed connective tissue disease, scleroderma, rheumatoid arthritis, etc.);
• Severe hepatic dysfunction (total bilirubin exceeding 14mg/L, AST or ALT exceeding 1.5 times the upper limit of normal) or estimated glomerular filtration rate (eGFR) ≤45ml/min per 1.73 m2;
• Severe and uncontrollable cardiovascular disease, neurological disease, lung disease, endocrine or gastrointestinal disease;
• Any substantial organ surgery performed within 12 weeks prior to screening is not tolerated by the test, or elective surgery is required during the study period;
• A history of malignant tumors, including solid tumors and malignant hematological tumors (except resected or cured basal cell carcinoma of the skin, squamous cell carcinoma and cervical intraepithelial neoplasia);
• A history of bone marrow, lung, liver, pancreas, or small intestine transplantation;
• A current or recent (within 4 weeks prior to enrollment) history of serious active or recurrent bacterial, viral, fungal, parasitic or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, hepatitis B and C, HIV infection, shingles, but not tinea onychomycosis);
• Had received live vaccine within 12 weeks prior to enrollment, or expected to require/receive live vaccine (other than shingles vaccine) during the study period;
• Suffering from a serious mental illness (e.g. schizophrenia, bipolar personality disorder) that affects communication and decision-making;
• Patients with severe allergies, who have a history of allergies to biological products, hypersensitivity reactions or other serious reactions;
• Participate in other clinical trials within 30 days before enrollment.

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

MeSH Terms

Conditions

Lupus Nephritis

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Xiangmei Chen

  Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiangmei Chen

CONTACT

86-10-66935462; xmchen301@126.com

Xueyuan Bai

CONTACT

86-13521203523; xueyuan_bai@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Chief physician, Academician of Chinese Academy of Engineering

Study Record Dates

• First Submitted: June 15, 2024
• First Posted: July 3, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2029
• Last Updated: July 3, 2024

Record last verified: 2024-06