Clinical Study of MMF in Treatment of IIM-ILD and Its Effect on Peripheral Blood Treg Cells

Sponsor
First Affiliated Hospital Xi'an Jiaotong University (Other)
Overall Status
Recruiting
CT.gov ID
NCT05129410
Collaborator
(none)
20
1
1
35.9
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Study Details

Study Description

Brief Summary

Interstitial lung disease (ILD) is a common pulmonary manifestation of idiopathic inflammatory myopathy (IIM). The overall 5-year mortality is 50%. The prognosis is poor and the treatment is challenging.At present, according to the consensus of IIM-ILD experts, glucocorticoids as first-line treatment are often used in high doses and have a variety of adverse reactions. Previous studies have shown that cyclophosphamide (CYC) is effective for IIM-ILD and tends to be used in rapidly progressive interstitial lung disease(RP-ILD)or refractory ILD. However, CYC is an alkylating agent with many toxic and side effects. It is prone to gonadal inhibition, infection, tumor, hemorrhagic cystitis and other risks. At present, Mycophenolate mofetil (MMF) has been widly used in the treatment of IIM, systemic lupus erythematosus (SLE), ANCA associated vasculitis (AAV). The observational research on MMF in the treatment of IIM-ILD shows that it can delay the progress of pulmonary fibrosis and can be used as the first-line treatment of IIM-ILD. Moreover, immune tolerance caused by defects in the number and/or quality of regulatory T cells (Treg) is considered to be a key source of autoimmune diseases. However, it is unclear whether MMF can improve the immune status of IIM-ILD by increasing Treg cells. The aim of this study was to evaluate the effect of MMF for IIM-ILD and its effcts on Treg through a prospective open single arm study, and provide a theoretical basis for the individualized treatment of IIM-ILD, which has important clinical significance.

Condition or Disease Intervention/Treatment Phase
  • Drug: Mycophenolate Mofetil
Phase 4

Detailed Description

Interstitial lung disease (ILD) is a common pulmonary manifestation of idiopathic inflammatory myopathy (IIM), with an incidence ranging from 23.1 to 65%. The treatment of IIM patients with ILD is challenging, and the overall 5-year mortality is 50%. The disease process of ILD from stable or slow to rapid. Increased mortality and poor prognosis were observed, which needs active treatment. At present, according to the consensus of IIM-ILD experts, glucocorticoids as first-line treatment are often used in high doses, but have a variety of adverse reactions. Previous studies have shown that cyclophosphamide (CYC) is effective for IIM-ILD and tends to be used in rapidly progressive interstitial lung disease(RP-ILD)or refractory ILD. However, CYC is an alkylating agent with many toxic and side effects. It is prone to gonadal inhibition, infection, tumor, hemorrhagic cystitis and other risks. Mycophenolate mofetil (MMF) has been widly used in the treatment of IIM, systemic lupus erythematosus (SLE), ANCA associated vasculitis (AAV). The observational research on MMF in the treatment of IIM-ILD shows that it can delay the progress of pulmonary fibrosis and can be used as the first-line treatment of IIM-ILD. Moreover, immune tolerance caused by defects in the number and / or quality of regulatory T cells (Treg) is considered to be a key source of autoimmune diseases. In transplant patients, studies have found that the combination of MMF and tacrolimus can increase the number of Treg cells in peripheral blood, suggesting that MMF has a certain regulatory effect on Treg cells. Therefore, it is unclear whether MMF can improve the immune status of IIM-ILD by increasing Treg cells, so as to improve the prognosis of the disease. However, it is unclear whether MMF can improve the immune status of IIM-ILD by increasing Treg cells. The aim of this study was to evaluate the effect of MMF for IIM-ILD and its effcts on Treg through a prospective open single arm study, and provide a theoretical basis for the individualized treatment of IIM-ILD.This was a single-arm open-label pilot observational study. Patients were received prednisone (0.5mg-1.0mg/kg/d ) combined with MMF(1.5g-2.0g/d) for 12 months, 4 weeks later, reduced 5mg every two weeks to 10mg/d orally for 3 months, gradually reduced to 7.5mg/ day until 12 months.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
20 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
A single-arm open-label pilot observational studyA single-arm open-label pilot observational study
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Clinical Study of MMF in Treatment of IIM-ILD and Its Effect on Peripheral Blood Treg Cells
Actual Study Start Date :
Dec 1, 2020
Anticipated Primary Completion Date :
Nov 30, 2022
Anticipated Study Completion Date :
Nov 30, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: A single-arm open-label pilot observational study

Patients were received prednisone(0.5mg-1mg/kg/day) and a combination with MMF (1.5g-2.0g/d).

Drug: Mycophenolate Mofetil
Prednisone 0.5-1.0 mg/kg/d, the dose was gradually reduced, and after 4 weeks, the dose was reduced by 5mg every two weeks, and then reduced to 10mg/d for 4-6 months after oral administration for 3 months, and then reduced to 7.5mg/d for maintenance therapy until 12 months; MMF1.5g-2.0g/d

Outcome Measures

Primary Outcome Measures

  1. FVC % predicted [12 months]

    Percentage of predicted FVC

Secondary Outcome Measures

  1. DLCO % predicted [12 months]

    Percentage of predicted DLCO

  2. Lung high resolution CT score [12 months]

    Lung high resolution CT score

  3. TDI [12 months]

    Transitional dyspnoea index

  4. TIS [12 months]

    Clinical response

  5. Overall survival rate [12 months]

    Overall survival rate%

  6. Infection rate [12 months]

    Infection rate%

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • meet the PM/DM diagnostic criteria according to Bohan-Peter

  • consistent with ILD diagnosis

  • predicted forced vital capacity (FVC) of at least 50%

  • patients who did not use immunosuppress agents (including but not limited to cyclophosphamide, cyclosporine, leflunomide, azathioprine, tacrolimus, etc.) at the time of screening, or who had stopped taking drugs for ≥3 months.

Exclusion Criteria:
  • Anti MDA5 antibody positive DM and necrotizing myopathy

  • patients if they had other connective tissue diseases, an underlying cancer, a concomitant active infection.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Department of Rheumatology,the First Affiliated Hospital of Xi'an Jiaotong University Xi'an China 710061

Sponsors and Collaborators

  • First Affiliated Hospital Xi'an Jiaotong University

Investigators

  • Study Chair: Lan He, First Affiliated Hospital Xi'an Jiaotong University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
First Affiliated Hospital Xi'an Jiaotong University
ClinicalTrials.gov Identifier:
NCT05129410
Other Study ID Numbers:
  • XJTU1AF2020LSK-194
First Posted:
Nov 22, 2021
Last Update Posted:
Nov 22, 2021
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Keywords provided by First Affiliated Hospital Xi'an Jiaotong University
Additional relevant MeSH terms:

Study Results

No Results Posted as of Nov 22, 2021