SMART-RA: Dynamic Treatment Regiments for Glucocorticoid Tapering
Study Details
Study Description
Brief Summary
The purpose of this clinical trial is to better understand how people with rheumatoid arthritis (RA) respond to gradual dose reduction, or "tapering", of steroid medications like prednisone. Some people with RA have symptoms when steroid dose is reduced, while others don't. This trial will look at different patient characteristics, including levels of inflammation in the body, differences in the way the brain processes sensory information, and certain hormone levels, to help researchers better understand why different people have these different responses to steroid tapering.
The hypotheses include:
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Greater or equal to ( ) 30% of participants in each arm will develop taper intolerance (either subjective, objective, or both) during the study period
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Greater or equal to 60% of participants will reduce Glucocorticoid dose by at least 5 Milligrams per day during the study period
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 15-day taper prednisone This will be for 30 days. Participants will be allocated to the 15-day strategy preferentially until enrollment goals have been met; once completing the 15-day strategy, many participants will also be eligible to complete the 150-day strategy, and may subsequently enroll in it if they wish. Participants that are not eligible for the 15-day strategy, but are eligible for the 150-day strategy, will be enrolled in the 150-day strategy. |
Drug: Oral prednisone Taper
The one group (15-day taper) will have approximately 50% oral prednisone dose reduction over 15 days. The other group 150-day taper will assess the effect of reducing oral prednisone by 1 milligram (mg) every 30 days over 150 days. The 15-day taper group and 150 day taper group will be followed for an additional 15 and 30 days, respectively, after the last dose reduction.
Other Names:
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| Experimental: 150-day taper prednisone This will be for 180 days. Participants who are not eligible for the 15-day strategy, but are eligible for the 150-day strategy, will be enrolled in the 150-day strategy. |
Drug: Oral prednisone Taper
The one group (15-day taper) will have approximately 50% oral prednisone dose reduction over 15 days. The other group 150-day taper will assess the effect of reducing oral prednisone by 1 milligram (mg) every 30 days over 150 days. The 15-day taper group and 150 day taper group will be followed for an additional 15 and 30 days, respectively, after the last dose reduction.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Taper intolerance - subjective [Day 30 (15-day taper) or day 180 (150-day taper group)]
Subjective intolerance, the first point when a participant elects to stop glucocorticoid taper due to associated symptoms.
- Taper intolerance -objective [Day 30 (15-day taper) or day 180 (150-day taper group)]
The first point when a participant develops any one of: increased RA activity (clinical disease activity index [CDAI] increase >2); RA flare (CDAI increase > 1 at a time when participant classifies as flaring); Clinical adrenal insufficiency.
- Net glucocorticoid dose reduction [Day 30 (15-day taper) or day 180 (150-day taper group)]
The difference (in mg/day) between a participant's prednisone dose at enrollment, and either (1) the dose at which participants first develop taper intolerance, or (2) the dose at the end of study involvement, if participants do not develop taper intolerance.
Eligibility Criteria
Criteria
Inclusion Criteria:
Ability to read and speak English to allow for written informed consent and patient-reported outcomes measures.
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Provision of signed and dated informed consent form
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Stated willingness to comply with all study procedures and availability for the duration of the study
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Ability to take oral medication and be willing to adhere to the study intervention regimen
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Diagnosis of rheumatoid arthritis by a medical provider, confirmed by checking medical records.
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Current use of an RA treatment regimen of both oral prednisone and 1 other Food and Drug Administration-approved disease-modifying antirheumatic drug (DMARD), with no change in this therapy over the past 90 days
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Eligible DMARDs include the following: hydroxychloroquine, sulfasalazine, methotrexate, leflunomide, etanercept, adalimumab, infliximab, golimumab, certolizumab pegol, abatacept, tocilizumab, sarilumab, rituximab, tofacitinib, baricitinib, upadacitinib
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Patients enrolling in the 15-day taper must be taking 7.5mg/day oral prednisone
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Patients enrolling in the 150-day taper must be taking 5mg/day oral prednisone
Exclusion Criteria:
Current or recent (past year) use of systemic glucocorticoid (oral, intravenous, or intramuscular administration) >2 weeks for an indication other than RA, to reduce risk of adverse health outcomes related to worsening of the indicated condition
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High RA disease activity, defined as a Clinical Disease Activity Index of greater (>) 10, given high likelihood of taper failure in this population due to increased RA activity alone
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Pre-existing primary or secondary adrenal insufficiency diagnosed by a physician, given high risk of worsening with prednisone taper
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Treatment with another investigational drug or intervention within 90 days
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Pregnancy
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Any impairment, activity, behavior, or situation that in the judgment of the study team would prevent satisfactory completion of the study protocol
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | VA Ann Arbor Healthcare System, Ann Arbor, MI | Ann Arbor | Michigan | United States | 48105-2303 |
Sponsors and Collaborators
- VA Office of Research and Development
Investigators
- Principal Investigator: Beth Wallace, MD MSc, VA Ann Arbor Healthcare System, Ann Arbor, MI
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IMMA-010-21S
- CX002430