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Low-dose Methotrexate for Change in Global Initiative for Asthma Step 5 Medications in Chronic Severe Asthma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02124226
Recruitment Status : Not yet recruiting
First Posted : April 28, 2014
Last Update Posted : April 23, 2019
Information provided by (Responsible Party):
Riccardo Polosa, Universita degli Studi di Catania

Brief Summary:

Patients with chronic severe asthma (CSA) have a crippling disease and current available treatments are not satisfactory. Thus, management of CSA remains a major unmet need. Although the evidence from existing randomized controlled trials fails to support a definite role for immunomodulatory drugs in these patients due to major methodologic drawbacks, findings with low-dose methotrexate (MTX) are encouraging. However, larger and well designed clinical trials are required to establish the beneficial role of MTX in CSA and for the detection of the key characteristics of those who are going to respond to this drug.

This study will be the first multi-centre RCT investigating the role of an add-on immunological modifier as a clinically useful therapeutic strategy in patients with well-phenotyped chronic severe asthma. As such, this study does not overlap with any other research currently ongoing.

Condition or disease Intervention/treatment Phase
Low Dose Methotrexate in Severe Chronic Asthma Drug: Methotrexate Drug: Placebo Phase 3

Detailed Description:

Patients will be recruited from the accessible asthmatic patients lists of tertiary referral centers. All patients will meet the stringent diagnostic criteria for CSA, including the requirement for the regular use of Step 5 medications (i.e. oral prednisone and/or omalizumab). The experimental design of the proposed study will take the form of a double-blind parallel-randomized placebo-controlled trial consisting of a total of eight visits including run-in and run-out periods. Patients will be randomly allocated to receive either MTX or matched placebo once a week as add-on therapy to their existing medication after run-in. Physiological, laboratory and clinical assessments will be measured regularly throughout the study and compared with baseline assessments.

We expect that MTX will reduce Step 5 medications dosage in patients with CSA without compromising the overall disease control. Improvement in several indicators of asthma severity and control will be also investigated

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 102 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: Low-dose Methotrexate for Change in Global Initiative for Asthma Step 5 Medications in Chronic Severe Asthma: a Randomized Controlled Trial
Estimated Study Start Date : April 2020
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Experimental: Methotrexate
Starting dose of 7.5 mg/week + folic acid the day after for 3 weeks as add-on therapy to their existing medication. Study treatment dosage will be increased, the maintenance dose will be 10 mg/week + folic acid the day after for 27 weeks
Drug: Methotrexate
7.5 mg/week + folic acid the day after
Other Name: Several brand names

Placebo Comparator: Matched placebo
Placebo pills
Drug: Placebo
matched placebo
Other Name: matched placebo

Primary Outcome Measures :
  1. At least 50% reduction in total dosage of GINA step 5 medications [ Time Frame: 80 weeks ]

Secondary Outcome Measures :
  1. clinically significant changes in clinimetric scores [ Time Frame: 80 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. patients with a diagnosis of CSA taking GINA Step 5 medications (i.e. regular OCS and/or omalizumab for a minimum of 6 months);
  2. failure in weaning patients completely from Step 5 medications during run-in;
  3. male and female individuals age 18 - 75 years;
  4. patients must be able to provide consent;

Exclusion Criteria:

  1. use of immunomodulatory therapies in the preceding 3 months;
  2. recent or current history of alcoholism;
  3. high liver enzyme levels (greater than 2.5 times the upper limit of the normal range);
  4. serum creatinine levels greater than 2.0 mg/dL
  5. acute illness within 15 days of study medication administration;
  6. leucopenia (below 3.0x109/L) and/or thrombocytopenia (below 100x109/L).
  7. pregnancy or planning to become pregnant;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02124226

Sponsors and Collaborators
Universita degli Studi di Catania
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Principal Investigator: Riccardo Polosa, Full Professor Universita di Catania

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Riccardo Polosa, Professor, Universita degli Studi di Catania Identifier: NCT02124226    
Other Study ID Numbers: METGINA-005
First Posted: April 28, 2014    Key Record Dates
Last Update Posted: April 23, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Riccardo Polosa, Universita degli Studi di Catania:
Chronic severe asthma, immunomodulation, methotrexate, steroids, omalizumab
Additional relevant MeSH terms:
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Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors