Clinical trial NCT06072768: Dynamic Treatment Regiments for Glucocorticoid Tapering
Official title: Using SMART Design to Develop Dynamic Treatment Regimens for Glucocorticoid Tapering
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Disease-modifying anti-rheumatic drug
Oral prednisone
Dose reduction
Tapering
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: University of Michigan
First posted: 2023-10-10
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: HEALTH_SERVICES_RESEARCH

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:

* Greater or equal to ( ) 30% of participants in each arm will develop taper intolerance (either subjective, objective, or both) during the study period
* Greater or equal to 60% of participants will reduce Glucocorticoid dose by at least 5 Milligrams per day during the study period

Detailed description: This trial was changed, so that participants could participate remotely without coming into the clinic. For participants coming into the clinic, the clinical disease activity index (CDAI) will be used to measure objective intolerance to tapering.

For remote participants, the Rheumatoid Arthritis Disease Activity Index (RADAI) will be used instead of the CDAI.

Eligibility criteria: Inclusion Criteria:

Ability to read and speak English to allow for written informed consent and patient-reported outcomes measures.

* Provision of signed and dated informed consent form
* Stated willingness to comply with all study procedures and availability for the duration of the study
* Ability to take oral medication and be willing to adhere to the study intervention regimen
* Diagnosis of rheumatoid arthritis by a medical provider, confirmed by checking medical records.
* 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

  1. Eligible DMARDs include the following: hydroxychloroquine, sulfasalazine, methotrexate, leflunomide, etanercept, adalimumab, infliximab, golimumab, certolizumab pegol, abatacept, tocilizumab, sarilumab, rituximab, tofacitinib, baricitinib, upadacitinib
  2. Patients enrolling in the 15-day taper must be taking 7.5mg/day oral prednisone
  3. 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

* Patients with greater than moderate RA activity as determined by the Clinical Disease Activity Index or by rheumatologist assessment, given high likelihood of taper failure in this population due to increased RA activity alone.
* Pre-existing primary or secondary adrenal insufficiency diagnosed by a physician, given high risk of worsening with prednisone taper
* Treatment with another investigational drug or intervention within 90 days
* Pregnancy
* Self-reported medical or psychiatric conditions that in the judgment of study personnel would preclude participation in this study (e.g., schizophrenia, malignancy, psychosis, suicidal ideation, history of substance abuse; note that stable anxiety and depression are NOT exclusions)
* Current, recent (within the last 6 months), or habitual use of artificial nails or nail enhancements. (Artificial nails can influence pressure pain sensitivity at the thumbnail);
* Any impairment, activity, behavior, or situation that in the judgment of the study team would prevent satisfactory completion of the study protocol

Primary outcomes:
measure: Number of participants with subjective taper intolerance
timeFrame: Day 30 (15-day taper) or day 180 (150-day taper group)
measure: Number of participants with objective taper intolerance
timeFrame: Day 30 (15-day taper) or day 180 (150-day taper group)
measure: Net glucocorticoid dose reduction
timeFrame: Day 30 (15-day taper) or day 180 (150-day taper group)
Secondary outcomes:
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: VA Ann Arbor Healthcare System, Ann Arbor, MI
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: VA Ann Arbor Healthcare System, Ann Arbor, MI
name: Beth Wallace, MD MSc
role: PRINCIPAL_INVESTIGATOR
References: