Dynamic Treatment Regiments for Glucocorticoid Tapering

Rheumatoid Arthritis Clinical Trial

— SMART-RA  

Official title:

Using SMART Design to Develop Dynamic Treatment Regimens for Glucocorticoid Tapering

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06072768
• Other study ID #: IMMA-010-21S
• Secondary ID: CX002430
• Status: Recruiting
• Phase: Phase 2
• Start date: March 9, 2023
• Est. completion date: March 1, 2030

Study information

• Verified date: May 2024
• Source: VA Office of Research and Development
• Contact: Olivia B Dickinson, BA
• Phone: (734) 548-2987
• Email: Olivia.Dickinson[@]va.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: March 1, 2030
• Est. primary completion date: March 1, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• 15-day taper prednisone
The 15-day taper group will assess the effect of an approximately 50% oral prednisone dose reduction over 15 days, and will be followed for an additional 15 days after the last dose reduction.
• 150-day taper prednisone
The 150-day taper group will assess the effect of reducing oral prednisone by 1 milligram (mg) every 30 days over 150 days, and will be followed for an additional 30 days after the last dose reduction.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	VA Ann Arbor Healthcare System, Ann Arbor, MI	Ann Arbor	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with subjective taper intolerance	Subjective intolerance, the first point when a participant replies elects to stop glucocorticoid taper due to associated symptoms. This will be assessed using a one-question questionnaire with binary "yes" and "no" responses.	Day 30 (15-day taper) or day 180 (150-day taper group)
Primary	Number of participants with objective taper intolerance	The first point when a participant develops any one of: increased RA activity (either clinical disease activity index [CDAI] increase of >2, or rheumatoid arthritis disease activity index [RADAI] of 1.5); RA flare (either CDAI increase of >1, or RADAI increase of >1 at a time when participant classifies as flaring; Clinical adrenal insufficiency.	Day 30 (15-day taper) or day 180 (150-day taper group)
Primary	Net glucocorticoid dose reduction	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.	Day 30 (15-day taper) or day 180 (150-day taper group)