Suggested immobilization test in RLS clinical trials: A systematic review and methodological appraisal

Background

The suggested immobilization test investigates restless legs syndrome symptoms in a controlled environment. Given the procedure's unique features and strengths, we traced its methodological evolution, investigated its utilization in RLS efficacy trials, and compared SIT metrics with conventional outcome measures.

Methods

We registered the study in PROSPERO (CRD42024542580). A systematic review was performed using four databases (PubMed, Embase, Web of Science, and Cochrane databases) from inception to January 2024. RLS placebo-controlled randomized controlled trials that used SIT were included in the final review. Cohen's d effect size was calculated for the outcome measures to standardize and compare IRLS and PSG PLMI with discomfort score and PLMI on SIT. A narrative review of SIT was also performed to analyze the methodological evolution.

Results

Eight hundred eighty-two studies were screened, and nine RCTs were included in this systematic review. Since its inception in 1988, the methodology has evolved over the years, including multiple SITs to capture circadian fluctuations and a refined discomfort scale. The majority of RCTs were performed in Europe, and only one RCT with SIT was conducted in the USA. Cohen's effect size analysis suggested the superior performance of the SIT PLM index over PLMSI on PSG, while IRLS captured a larger effect size compared to SIT DS.

Conclusion

Despite robust assessment of current RLS symptoms by SIT/mSIT, they remain underutilized in RLS efficacy trials. mSIT captures all RLS features in a controlled environment, and it adds depth, precision and critical complementary data to conventional RLS outcome measures in RLS treatment evaluations.