Rheumatoid ArthritisPhase 4NCT00695188
Methotrexate Polyglutamate Levels as a Marker for the Clinical Outcome in the Treatment of Rheumatoid Arthritis
A Phase 4 study testing methotrexate in people with Rheumatoid Arthritis, run by Ludwig-Boltzmann Institut fuer Rheumatologie, Balneologie und Rehabilitation at 2 sites in Austria.
Trial summary
The primary objective is to determine whether erythrocyte polyglutamate levels are associated with objective clinical response in patients with rheumatoid arthritis after oral administration of low-dose methotrexate.The secondary aim of this study is to compare the efficacy and safety of standard dose methotrexate… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- methotrexate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 2 sitesAustria
- Study dates
- May 2008to Dec 2010
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- MTX-naive
- Age > 18 years
- DAS-28 > 3.2
- American College of Rheumatology-criteria for RA
- Chest-X-ray
- Informed consent
- Prednisolon < 10 mg a day
Who cannot join
- Pregnancy
- Lactation
- Renal and hepatic impairment
- Malignant diseases (last 5 years)
- Contraindications
- Human Immunodeficiency Virus (HIV), Hepatitis B and C
Trial locations and contacts
2 sites in 1 country.
Austria2 sites
Kaiser-Franz-Josef-Spital
Vienna, 1100
Rheumazentrum Wien Oberlaa
Vienna, 1100
About this study
Official title: Methotrexate Polyglutamate Levels as a Marker for the Clinical Outcome in the Treatment of Rheumatoid Arthritis A Multicenter, Randomized, Double-blind, Controlled Phase IV Trial
The primary objective is to determine whether erythrocyte polyglutamate levels are associated with objective clinical response in patients with rheumatoid arthritis after oral administration of low-dose methotrexate.The secondary aim of this study is to compare the efficacy and safety of standard dose methotrexate versus a higher starting dose.
Read the detailed description
The folate antagonist methotrexate (MTX) is currently one of the most widely used drugs for the treatment of rheumatoid arthritis (RA).Although MTX is very effective and well tolerated, the major drawback is the large interpatient variability in the clinical response.MTX is intracellularly converted by folylpolyglutamate synthetase (FPGS) to methotrexate polyglutamates (MTXPGs), which enhance the intracellular retention of MTX. Furthermore, the γ-linked sequential addition of glutamic acid residues inhibits finals steps in the de novo purine and pyrimidine biosynthesis, resulting in anti-proliferative and anti-inflammatory effects.76 adult, MTX-naive patients who fulfill the American College of Rheumatology criteria (ACR) for RA with a Disease Activity Score in 28 joints (DAS-28) > 3.2 are enrolled at two sites in Vienna (Austria).Clinical status is assessed by the number of joint counts and the Health Assessment Questionnaire (HAQ).Patients are randomly assigned to receive either a standard dose or a higher starting dose of 25 mg orally. In week 5, a subcutaneous dose of 25 mg is administered to each patient to get a reference level (bioavailability of 100%).The patients participate for 16 weeks, in which blood samples are collected at weeks 1, 2, 5, 6, 10 and 11 to perform pharmacokinetic analyses and metabolite measurements.The determination of erythrocyte MTXPG-levels is performed by using a HPLC technique.The primary outcome is the objective clinical response (measured in a rheumatic score, DAS-28), secondary outcome parameters are quality of life and routine laboratory parameters used in rheumatology. This clinical outcome will be correlated with MTX pharmacokinetics in blood, MTXPG kinetics in erythrocytes, and their impact on the folate pathway.
- Conditions
- Rheumatoid Arthritis
- Being tested
- methotrexate
- Keywords
- rheumatoid arthritis, MTX polyglutamates, clinical outcome
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
methotrexateDrug
oral administration Escalating dose (15, 20, 25 mg)
methotrexateDrug
25 mg oral administration
| Study group | Role | What they receive |
|---|---|---|
| Standard dose | Other | Escalating dose Receives: Drug: methotrexate |
| High dose | Active comparator | 25 mg Receives: Drug: methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
DAS-28 (Disease Activity Score in 28 Joints)
DAS stands for "Disease Activity Score" and is a measure of the activity of rheumatoid arthritis. In Europe the DAS is the recognized standard in research and clinical practice.
The following parameters are included in the calculation:
- Number of joints tender to the touch (TEN)
- Number of swollen joints (SW)
- Erythrocyte sedimentation rate (ESR)
- Patient assessment of disease activity (VAS; mm)
The DAS-28 is evaluated using a scale:
0 - 3.2: low disease activity 3.2 - 5.1: moderate disease activity > 5.1: severe disease activity
Measured: 16 weeks
Secondary outcomes (1)
HAQ (Health Assessment Questionnaire)
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2008 (estimated)
- Study startMay 2008
- Primary completionDec 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ludwig-Boltzmann Institut fuer Rheumatologie, Balneologie und Rehabilitation
- Sponsor type
- University, hospital or other
- Investigators
- Hans Broell, Prof. Dr., Principal investigator, Ludwig-Boltzmann-Institut fuer Rheumatologie und Balneologie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00695188
- Sponsor's protocol ID
- PROMTX2007_01
- Other IDs
- EudraCT: 2007-006288-56
- Status last verified
- Aug 2009
- First submitted
- 9 Jun 2008
- Last updated
- 17 Feb 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Hobl EL, Mader RM, Jilma B, Duhm B, Mustak M, Broll H, Hogger P, Erlacher L. A randomized, double-blind, parallel, single-site pilot trial to compare two different starting doses of methotrexate in methotrexate-naive adult patients with rheumatoid arthritis. Clin Ther. 2012 May;34(5):1195-203. doi: 10.1016/j.clinthera.2012.03.059. Epub 2012 Apr 18.
PubMed 22516039
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Methotrexate Polyglutamate Levels as a Marker for the Clinical Outcome in the Treatment of Rheumatoid Arthritis A Multicenter, Randomized, Double-blind, Controlled Phase IV Trial
- ClinicalTrials.gov ID
- NCT00695188
- Acronym / sponsor ID
- PROMTX2007_01
- Conditions
- Rheumatoid Arthritis
- Keywords
- rheumatoid arthritis, MTX polyglutamates, clinical outcome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Ludwig-Boltzmann Institut fuer Rheumatologie, Balneologie und RehabilitationUniversity, hospital or other
- Study start
- May 2008
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 11 Jun 2008 (estimated)
- Results
- Posted 15 Feb 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective is to determine whether erythrocyte polyglutamate levels are associated with objective clinical response in patients with rheumatoid arthritis after oral administration of low-dose methotrexate.The secondary aim of this study is to compare the efficacy and safety of standard dose methotrexate versus a higher starting dose.
Detailed description
The folate antagonist methotrexate (MTX) is currently one of the most widely used drugs for the treatment of rheumatoid arthritis (RA).Although MTX is very effective and well tolerated, the major drawback is the large interpatient variability in the clinical response.MTX is intracellularly converted by folylpolyglutamate synthetase (FPGS) to methotrexate polyglutamates (MTXPGs), which enhance the intracellular retention of MTX. Furthermore, the γ-linked sequential addition of glutamic acid residues inhibits finals steps in the de novo purine and pyrimidine biosynthesis, resulting in anti-proliferative and anti-inflammatory effects.76 adult, MTX-naive patients who fulfill the American College of Rheumatology criteria (ACR) for RA with a Disease Activity Score in 28 joints (DAS-28) > 3.2 are enrolled at two sites in Vienna (Austria).Clinical status is assessed by the number of joint counts and the Health Assessment Questionnaire (HAQ).Patients are randomly assigned to receive either a standard dose or a higher starting dose of 25 mg orally. In week 5, a subcutaneous dose of 25 mg is administered to each patient to get a reference level (bioavailability of 100%).The patients participate for 16 weeks, in which blood samples are collected at weeks 1, 2, 5, 6, 10 and 11 to perform pharmacokinetic analyses and metabolite measurements.The determination of erythrocyte MTXPG-levels is performed by using a HPLC technique.The primary outcome is the objective clinical response (measured in a rheumatic score, DAS-28), secondary outcome parameters are quality of life and routine laboratory parameters used in rheumatology. This clinical outcome will be correlated with MTX pharmacokinetics in blood, MTXPG kinetics in erythrocytes, and their impact on the folate pathway.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard dose | Other | Drug: methotrexateEscalating dose |
| High dose | Active comparator | Drug: methotrexate25 mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- MTX-naive
- Age > 18 years
- DAS-28 > 3.2
- American College of Rheumatology-criteria for RA
- Chest-X-ray
Key exclusion criteria (6 listed)
- Pregnancy
- Lactation
- Renal and hepatic impairment
- Malignant diseases (last 5 years)
- Contraindications
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| methotrexateoral administration Escalating dose (15, 20, 25 mg) | Drug | Standard dose |
| methotrexate25 mg oral administration | Drug | High dose |
Primary outcome
DAS-28 (Disease Activity Score in 28 Joints)
Time frame: 16 weeks
DAS stands for "Disease Activity Score" and is a measure of the activity of rheumatoid arthritis. In Europe the DAS is the recognized standard in research and clinical practice. The following parameters are included in the calculation: * Number of joints tender to the touch (TEN) * Number of swollen joints (SW) * Erythrocyte sedimentation rate (ESR) * Patient assessment of disease activity (VAS; mm) The DAS-28 is evaluated using a scale: 0 - 3.2: low disease activity 3.2 - 5.1: moderate disease activity > 5.1: severe disease activity
1 secondary outcome
HAQ (Health Assessment Questionnaire)
Time frame: 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22516039Hobl EL, Mader RM, Jilma B, Duhm B, Mustak M, Broll H, Hogger P, Erlacher L. A randomized, double-blind, parallel, single-site pilot trial to compare two different starting doses of methotrexate in methotrexate-naive adult patients with rheumatoid arthritis. Clin Ther. 2012 May;34(5):1195-203. doi: 10.1016/j.clinthera.2012.03.059. Epub 2012 Apr 18.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hans Broell, Prof. Dr. principal investigator
Ludwig-Boltzmann-Institut fuer Rheumatologie und Balneologie
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing methotrexate in people with Rheumatoid Arthritis, run by Ludwig-Boltzmann Institut fuer Rheumatologie, Balneologie und Rehabilitation at 2 sites in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Feb 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Feb 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DAS-28 (Disease Activity Score in 28 Joints) (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00695188, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2011.