Effect of pramipexole on RLS symptoms and sleep: a randomized, double-blind, placebo-controlled trial

BackgroundPatients with Restless Legs Syndrome (RLS) often seek treatment because of sleep problems related to nocturnal symptoms. Our goal was to test the ability of pramipexole to improve sleep in RLS patients and to reconfirm its efficacy for primary RLS symptoms.MethodsAdults with moderate or severe RLS were randomized to receive placebo or pramipexole (flexibly titrated from 0.25 to 0.75 mg), 2–3 h before bedtime for 12 weeks. The co-primary outcome measures were change in Medical Outcomes Study (MOS) sleep disturbance score and International RLS Study Group Rating Scale (IRLS) score at 12 weeks.ResultsThe intent-to-treat population included 357 patients: 178 received pramipexole and 179 received placebo. At 12 weeks, the adjusted mean change from baseline was greater for pramipexole (vs. placebo) for IRLS score (−13.4 ± 0.7 vs. −9.6 ± 0.7) and MOS sleep disturbance score (−25.3 ± 1.5 vs. −16.8 ± 1.5) (p ⩽ 0.0001; ANCOVA). Responder rates (clinical and patient global impression and IRLS) were also significantly higher in the pramipexole group. RLS-QOL score was improved over placebo at Week 12 (p < 0.01) as were MOS sleep adequacy (p = 0.0008) and quantity (p = 0.08) scores. Nine percent of patients in each group withdrew because of adverse events.ConclusionsPramipexole is effective and well-tolerated for RLS and related sleep disturbance.     

Clinical efficacy of ropinirole for restless legs syndrome is not affected by age at symptom onset

ObjectiveTo determine whether clinical response to the dopamine agonist, ropinirole, in the treatment of primary restless legs syndrome (RLS), depends upon the age-at-onset of RLS symptoms.MethodsPooled data from four 12-week, randomized, double-blind, placebo-controlled studies of ropinirole in patients with moderate-to-severe primary RLS were analyzed post hoc. The relationship between age-at-onset and response to treatment, based on change from the baseline International Restless Legs Syndrome Study Group (IRLSSG) rating scale (the International Restless Legs Scale [IRLS]) total score and the proportion of responders (rated ‘much’/‘very much’ improved) on the Clinical Global Impression–Improvement (CGI-I) scale, was explored.ResultsThe range of age-at-onset of RLS symptoms was 2–75 years. No relationship was observed between the age-at-onset of RLS symptoms and baseline IRLS total score (correlation r = −0.06), and between dose administered at Week 12 last observation carried forward (LOCF) and age-at-onset (r = −0.04). The age-at-onset by treatment interaction was non-significant (P = 0.952 for the IRLS and P = 0.716 for the CGI-I scale), indicating there was no significant relationship between age-at-onset and the magnitude of ropinirole treatment effect.ConclusionsThese data suggest that ropinirole provides effective relief of symptoms, regardless of age at RLS symptom onset.     

Efficacy of oral iron in patients with restless legs syndrome and a low-normal ferritin: A randomized, double-blind, placebo-controlled study

Background and PurposeRestless Legs Syndrome (RLS) is a primary disorder of sensation that affects sleep and has been associated with iron deficiency. The purpose of this study was to determine if symptomatic RLS patients with low-normal serum ferritin levels benefit from oral iron replacement.Patients and MethodsThis was a randomized, placebo-controlled, double-blinded study. Eligible patients were randomized to oral iron therapy vs. appearance-matched placebo and followed over a 12 week period.ResultsBaseline International Restless Leg Scale (IRLS) scores for the treatment (24.8 ± 5.72) and placebo (23.0 ± 5.03) groups were similar. Baseline ferritin levels for the treatment (40.6 ± 15.3 ng/ml) and placebo (36.7 ± 20.8 ng/ml) groups were also similar. After 12 weeks, IRLS scores decreased more in the treatment arm (10.3 ± 7.40) than in the placebo arm (1.14 ± 5.64), (p = 0.01). Ferritin levels increased more in the treatment arm (25.1 ± 20.3 ng/ml) than in the placebo arm (7.5 ± 13.7 ng/ml), (p = 0.04). We observed a nonsignificant trend toward improved quality of life in the treated patients, (p = 0.07).ConclusionsThis is the first double-blinded, placebo-controlled study to demonstrate statistically significant improvement in RLS symptoms using oral iron therapy in patients with low-normal ferritin. The findings from this study suggest that additional larger randomized placebo-controlled trials of iron as treatment for patients with low-normal ferritin are warranted.     

A randomized,double-blind, 6-week,dose-ranging study of pregabalin in patients with restless legs syndrome

ObjectiveThis study evaluated the dose-related efficacy and safety of pregabalin in patients with idiopathic restless legs syndrome (RLS).MethodsThis six-arm, double-blind, placebo-controlled, dose–response study randomized patients (N = 137) with moderate-to-severe idiopathic RLS in an equal ratio to placebo or pregabalin 50, 100, 150, 300, or 450 mg/day. The dose–response was characterized using an exponential decay model, which estimates the maximal effect (E_max) for the primary endpoint, the change in the International Restless Legs Study Group Rating Scale (IRLS) total score from baseline to week 6 of treatment. Secondary outcomes included Clinical Global Impressions-Improvement Scale (CGI-I) responders, sleep assessments, and safety.ResultsThe separation of treatment effect between placebo and pregabalin began to emerge starting at week 1 which continued and increased through week 6 for all dose groups. The IRLS total score for pregabalin was dose dependent and well characterized for change from baseline at week 6. The model estimated 50% (ED₅₀) and 90% (ED₉₀) of the maximal effect in reducing RLS symptoms that occurred at pregabalin doses of 37.3 and 123.9 mg/day, respectively. A higher proportion of CGI-I responders was observed at the two highest doses of pregabalin (300 and 450 mg/day) versus placebo. Dizziness and somnolence were the most common adverse events and appeared to be dose-related.ConclusionsIn this 6-week phase 2b study, pregabalin reduced RLS symptoms in patients with moderate-to-severe idiopathic RLS. The symptom reduction at week 6 was dose-dependent with 123.9 mg/day providing 90% efficacy. Pregabalin was safe and well tolerated across the entire dosing range.     

Relation of the International Restless Legs Syndrome Study Group rating scale with the Clinical Global Impression severity scale,the restless legs syndrome 6-item questionnaire,and the restless legs syndrome-quality of life questionnaire

BackgroundThe SP790 study (ClinicalTrials.gov, NCT00136045) showed benefits of rotigotine over placebo in improving symptom severity of restless legs syndrome (RLS), also known as Willis-Ekbom disease, on the International Restless Legs Syndrome Study Group rating scale (IRLS), Clinical Global Impression item 1 (CGI-1), RLS 6-item questionnaire (RLS-6), and the RLS-quality of life questionnaire (RLS-QoL) in patients with moderate to severe idiopathic RLS. To provide clinical context for the IRLS and to guide the choice of assessment scales for RLS studies, our post hoc analysis of SP790 data evaluated associations between the IRLS and the CGI-1, IRLS and RLS-6, and the IRLS and RLS-QoL.MethodsScale associations were analyzed at baseline and at the end of maintenance (EoM) using data from the safety set (rotigotine and placebo groups combined [n = 458]). Changes from baseline to EoM in IRLS score vs comparator scale scores also were analyzed.ResultsThere was a trend towards increasing IRLS severity category with increasing CGI-1, RLS-6, and RLS-QoL score. Pearson product moment correlation coefficients showed correlations between IRLS and comparator scale scores at baseline and EoM as well as correlations for change from baseline to EoM.ConclusionCorrelations between the IRLS and comparator scales were substantial. These data indicate that the IRLS is clinically meaningful. The IRLS and CGI-1 are generally sufficient to evaluate the overall severity and impact of RLS symptoms in clinical trials.     

Efficacy and safety of dopamine agonists in restless legs syndrome

ObjectiveRestless legs syndrome (RLS) is a common neurological disorder causing considerable impairment to daily living. This article is an overview of a comprehensive Cochrane meta-analysis on the efficacy and safety of dopamine agonists (DAs), the first-line treatment of RLS.MethodsCENTRAL, MEDLINE, EMBASE, PsycINFO, and CINAHL databases were searched for double-blind randomized controlled trials (RCTs) of DAs vs placebo.ResultsThirty-five placebo-controlled RCTs (total number of patients = 6954) were eligible. The likelihood of bias was considered to be low. The mean treatment duration of the RCTs was 10.3 (standard deviation 7.3) weeks, with treatment durations up to seven months. Overall, DAs showed a moderate improvement in the International RLS Severity Scale score (mean difference ?5.7 points [95% confidence interval, CI, ?6.7 to ?4.7; P < 0.00001]) and the Clinical Global Impression-Improvement response (risk ratio 1.44 [95% CI 1.34–1.54; P < 0.00001]) compared with placebo. Periodic limb movements decreased by ?22.38/h (95% CI ?27.8 to ?16.9; P < 0.00001) for DAs compared with placebo. Sleep quality and disease-specific quality of life increased slightly to moderately. Safety data confirmed the established safety characteristics of DAs. Augmentation, a specific side-effect of dopaminergic treatment of RLS, was not assessed adequately.ConclusionsThis meta-analysis showed that DAs have moderate efficacy in the treatment of RLS. Actively controlled and long-term studies are still lacking. Large-scale comparative studies are needed to identify the most efficient treatments for this chronic disorder.     

Ropinirole is effective in the treatment of restless legs syndrome. TREAT RLS 2: a 12-week, double-blind, randomized, parallel-group, placebo-controlled study.

Restless legs syndrome (RLS) is a neurological condition with significant impact on sleep and quality of life (QoL). This double-blind, randomized, 12-week, multinational study compared the efficacy and safety of ropinirole and placebo in RLS. In total, 267 outpatients with moderate-to-severe RLS were randomly assigned to ropinirole (0.25-4.0 mg/day) or placebo, 1 to 3 hours before bedtime. The primary endpoint was the change in International Restless Legs Scale (IRLS) score at week 12. Key secondary endpoints were the percentage of patients showing significant improvement on the Clinical Global Impression-Improvement (CGI-I) scale at week 12 and changes in IRLS and CGI-I scale scores at week 1. Other measures included the Medical Outcomes Study sleep scale and Restless Legs Syndrome Quality of Life questionnaire. Improvements were significantly greater for ropinirole than placebo for change in IRLS score at week 12 (-11.2 [SE 0.76] vs. -8.7 [0.75], respectively; adjusted treatment difference -2.5 [95% confidence interval [CI], -4.6, -0.4], P = 0.0197); all key secondary endpoints; sleep and QoL parameters. Adverse events were typical for dopamine agonists; disease augmentation, although not directly assessed, was not reported during treatment. Ropinirole improves symptoms, associated sleep disturbance, and QoL of RLS patients and is generally well tolerated.     

Restless Legs Syndrome and the five-factor model of personality: results from a community sample

ObjectiveTo examine personality characteristics as potential mediators of the association between Restless Legs Syndrome (RLS) and psychiatric disorders.MethodRevised NEO Personality Inventory traits are compared in respondents with (n = 42) versus without (n = 982) a diagnosis of RLS in a general population sample.ResultsRLS was associated with higher neuroticism after adjusting for potential confounders, including current psychopathology. Further analysis showed that the association between RLS and neuroticism contributes to, but does not fully explain, the relationship between RLS and either panic disorder or major depression.ConclusionsNeuroticism may mediate part of the relationship between RLS and depression or panic, but the mechanisms of these associations need further exploration.     

Restless legs syndrome in hemodialysis patients: an epidemiologic survey in Greece

BackgroundRestless legs syndrome (RLS) is a sensorimotor disorder characterized by an uncontrolled need to move extremities accompanied by unpleasant sensations, which frequently leads to sleep disturbances. In hemodialysis (HD) patients, the previously reported RLS prevalence varied enormously, between 6% and 60%. In our study, we investigated the RLS prevalence in HD patients for the first time in Greece.MethodsA continuous sample of HD patients was studied between January and September of 2010 in six dialysis units in Greece. RLS diagnosis was based on the essential clinical criteria of the International RLS Study Group (IRLSSG). The standardized incidence ratio (SIR) for RLS in HD patients was calculated in comparison to data from a recent survey of the general population in Greece.ResultsIn our study of 579 HD patients in Greece (236 women; mean age, 65 ± 13 years), the prevalence of RLS was elevated in comparison to the general population (26.6% vs 3.9%), with an SIR of 5.4 (95% confidence interval [CI], 4.6–6.3). In the fully adjusted model, the risk for RLS in HD patients was reduced in older age (odds ratio [OR], 0.98 [95% CI, 0.96–0.99]) and increased in women (OR, 1.60 [95% CI, 1.05–2.43]) in cases with elevated levels of β₂ microglobulin (OR, 1.15 [95% CI, 1.01–1.32]) and intact parathormone (iPTH) (OR, 1.30 [95% CI, 1.08–1.56]).ConclusionA high RLS prevalence was recorded in a large HD population in Greece, clearly suggesting the need for enhanced awareness of RLS in nephrology. The RLS risk was increased in women and in younger HD patients as well as in those with elevated β₂ microglobulin and iPTH levels.     

Investigating the response to intravenous iron in restless legs syndrome: an observational study

ObjectiveTo investigate the effect of intravenous (IV) iron (500 mg ferric carboxymaltose [FCM] as a single dose) on restless legs syndrome (RLS) severity on a day-to-day basis.MethodsTwenty patients with RLS and absolute or functional iron deficiency or low normal serum ferritin (<45 μg/l) were included. Change of RLS severity was evaluated using the International RLS severity scale (IRLS) and the RLS-severity diary (RLS-SD) which evaluates symptom severity over a 6-h period on an 11-point numerical Likert scale, four times a day.ResultsTwelve patients reported that IV FCM improved RLS (“responders”). IRLS score decreased from 30.1 (±5.9) to 23.07 (±9.5) (p = 0.001) in the whole group and from 28.3 (±6.1) to 18.3 (±8.0) (p = 0.002) in the responder group three weeks after IV FCM treatment. A clinically relevant effect of IV iron on RLS severity could be seen as early as day eight. The responder group differed from the non-responder group in tendency by being younger (p = 0.064), having a lower serum ferritin level at baseline (p = 0.097), and presenting a lower number of comorbid conditions.ConclusionsFCM led to a considerable improvement in RLS in the responder group within about one week. These findings are clinically relevant, especially for patients with severe RLS symptoms and iron deficiency, since a change or uptitration of RLS-specific medication can be avoided or postponed in these patients due to the rapid response to IV FCM treatment.     

Restless legs syndrome in Czech patients with multiple sclerosis: an epidemiological and genetic study

BackgroundRestless legs syndrome (RLS) is a frequent neurological disorder which is presented in idiopathic and secondary form. Idiopathic RLS is associated with common genetic variants in four chromosomal regions. Recently, multiple sclerosis (MS) was identified as a common cause for secondary RLS. The aim of our study was to evaluate the prevalence of RLS among Czech patients with MS and to further analyze the impact of known genetic risk factors for RLS in patients with MS.MethodsEach patient underwent a semi-structured interview. A patient was considered to be affected by RLS if all four standard criteria had ever been met in their lifetime. The sample was genotyped using 12 single nucleotide polymorphisms within the four genomic regions, which were selected according to the results of previous genome-wide association studies.ResultsA total of 765 subjects with MS were included in the study and the diagnosis of RLS was confirmed in 245 subjects (32.1%, 95% CI 28.7–35.4%). The genetic association study included 642 subjects; 203 MS patients with RLS were compared to 438 MS patients without RLS. No significant association with MEIS 1, BTBD9, and PTPRD gene variants was found despite sufficient statistical power for the first two loci. There was a trend for association with the MAP2K5/SCOR1 gene – the best model for the risk allele was the recessive one (p nominal = 0.0029, p corrected for four loci and two models = 0.023, odds ratio = 1.60).ConclusionWe confirmed that RLS prevalence was high in patients with multiple sclerosis, but this form did not share all genetic risk variants with idiopathic RLS.     

Efficacy and safety of pramipexole in Japanese patients with primary restless legs syndrome: A polysomnographic randomized,double-blind,placebo-controlled study

ObjectiveTo evaluate the efficacy of pramipexole on polysomnographic measures, patient ratings and a clinical rating in Japanese patients with primary restless legs syndrome (RLS).MethodsPatients with moderate to severe RLS having periodic limb movements in bed index (PLMI) ? 5 were randomly assigned to receive pramipexole or placebo in a 6-week, double-blind, placebo-controlled study with forced titration from 0.125 to 0.75 mg/day. Both polysomnography (PSG) and the suggested immobilization test (SIT) were performed at baseline and 6 weeks after starting treatment.ResultsThe analysis of covariance of log-transformed PLMI showed that the adjusted means at the end of study were significantly smaller in the pramipexole group than in the placebo group (p = 0.0019). In all patients, variables on SIT did not show any differences between the two groups, whereas a significant improvement was shown in the pramipexole group compared with the placebo group for patients with a SIT-PLM index at baseline ? 15. Pramipexole group showed a significant reduction in the International Restless Legs Syndrome Study Group rating scale (IRLS; p = 0.0005), a significant improvement in both Patient Global Impression (PGI; p < 0.0001) and Clinical Global Impressions (CGI-I; p = 0.0488), and a significantly greater mean reduction in the Pittsburgh Sleep Quality Index (PSQI; p = 0.0016), when compared with those of placebo group at week 6.ConclusionsPramipexole is highly efficacious in the reduction of PLMI and in the improvement of subjective severity of RLS and subjective sleep disturbance caused by the disorder.     

Restless legs syndrome in Chinese elderly people of an urban suburb in Shanghai: a community-based survey

ObjectiveThe aim of the study is to investigate the prevalence rate of restless legs syndrome (RLS) in elderly Chinese people over 50 years of age in an urban suburb of Shanghai by a community-based study.MethodsA 3-step survey was adopted including two telephone-based interviews and one face-to-face interview. We used questions based on four diagnostic criteria for RLS to perform the first telephone interview. The second telephone interview was performed by a sleep specialist to rule out the ‘mimics’ and secondary RLS. The final face-to-face interview was performed in the clinic for confirmation and examination.ResultsThere were 2609 inhabitants in the Wuli Bridge suburb of Shanghai who responded to the first telephone interview (men 68.55 ± 10.13 years of age and women 65.34 ± 10.52 years of age, mean ± SD). Eighteen people were finally diagnosed with RLS. In this sample, the overall prevalence rate of RLS was about 0.69% (95% confidence interval (CI): 0.41–1.09).ConclusionOur study provided the first data about the prevalence rate of RLS in an urban suburb of Shanghai from mainland China, which is consistent with the low prevalence rate reported in other Asian countries.     

Evaluation of oral iron treatment in pediatric restless legs syndrome (RLS)

ObjectiveWe conducted a retrospective chart review of children with restless legs syndrome (RLS) to evaluate the efficacy of oral iron treatment, which was administered open-label during the course of clinical care. In addition, we provided detailed clinical information about RLS in this pediatric cohort.Patients and methodsThe study included 30 consecutive Japanese children with RLS who visited the Pediatric Sleep Clinic at Osaka University Hospital, and consisted of 17 boys and 13 girls, aged 2–14 years (mean ± SD, 6.5 ± 2.8). All-night polysomnography was performed in 18 patients and serum ferritin levels were measured in all the patients. After the diagnosis of RLS, iron was administered at doses between 1.6 and 7.8 mg/kg/day (3.2 ± 1.3). Serum ferritin was re-evaluated 3–6 months after iron treatment, or when RLS symptoms had disappeared.ResultsThe patient age at onset of RLS symptoms ranged from six months to 13 years (4.3 ± 3.6). A positive family history was recognized in 19 children (63.3%). Serum ferritin levels before therapy were 9–62 ng/ml (26.6 ± 12.8) and oral iron supplementation was reported to be highly effective in 17 children, effective in 10, and ineffective in three. The serum ferritin level at follow-up was 23–182 ng/ml (83.5 ± 49.8). The onset of treatment effect was within approximately three months.ConclusionsIron treatment could be effective in Japanese pediatric RLS.     

Restless legs syndrome, sleep impairment, and fatigue in chronic obstructive pulmonary disease

ObjectiveTo investigate the frequency of factors associated with restless legs syndrome (RLS) in patients with chronic obstructive pulmonary disease (COPD).MethodsRLS diagnosis was investigated (International RLS Study Group, IRLSSG) and severity was assessed (IRLS rating scale) in 104 consecutive COPD patients (age 69.1 ± 8). Other measures were dyspnea severity (Modified Medical Research Council, MMRC), sleep quality (Pittsburgh Sleep Quality Index, PSQI), daytime somnolence (Epworth Sleepiness Scale, ESS), depressive symptoms (Beck Depression Inventory, BDI-II), and fatigue (Fatigue Severity Scale, FSS). Laboratory values included hemoglobin, ferritin, creatinine, and fibrinogen.ResultsThirty-two patients (30.8%) were diagnosed with RLS (65.6% women), which was moderate/severe (IRLS >11) in 26 (81.3%). RLS symptoms started after age 40 in most patients (93.3%). RLS patients had poorer sleep quality (PSQI >5 = 59.6%; p = 0.002), worse fatigue (FSS >27 = 51%; p = 0.005), and more depressive symptoms (BDI-II >10 = 14.4%; p = 0.005). Patients with RLS also presented more severe dyspnea (p = 0.009) and lower creatinine levels (p = 0.005). Overall, fatigue severity was correlated with older age (p = 0.001); level of dyspnea was positively correlated with PSQI and FSS (p < 0.005) and negatively correlated with ferritin (p = 0.03) and creatinine (p = 0.005), and PSQI scores correlated positively with FSS (p < 0.005) and negatively with ferritin (p = 0.005) and creatinine (p = 0.02). Quality of sleep was independently predicted by dyspnea severity and creatinine and fatigue by age and depression.ConclusionRLS is common in COPD. Patients with RLS have low creatinine, poorer quality of sleep, and more fatigue and depressive symptoms. RLS symptom severity is correlated to lower ferritin and severity of dyspnea.     

One year open-label safety and efficacy trial with rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome

BackgroundLong-term efficacy and tolerability data are not yet available for patch formulations of dopamine agonists in restless legs syndrome.MethodsEfficacy and safety of rotigotine (0.5–4 mg/24 h), formulated as a once-daily transdermal system (patch), were investigated in an open extension (SP710) of a preceding 6-week placebo-controlled trial (SP709, 341 randomized patients) in patients with idiopathic restless legs syndrome. For efficacy assessment the international RLS severity scale (IRLS), the RLS-6 scales, the clinical global impressions (CGI) and the QoL-RLS questionnaire were administered. In addition, long-term tolerability and safety were assessed.ResultsOf 310 patients who finished the controlled trial, 295 (mean age 58 ± 10 years, 66% females) with a mean IRLS score of 27.8 ± 5.9 at baseline of SP709 were included. We report results after one year of this ongoing long-term trial. Two hundred twenty patients (retention rate = 74.6%) completed the 12-month follow-up period. The mean daily dose was 2.8 ± 1.2 mg/24 h with 4 mg/24 h (40.6%) being the most frequently applied dose; 14.8% were sufficiently treated with 0.5 or 1.0 mg/24 h. The IRLS total score improved by −17.4 ± 9.9 points between baseline and end of Year 1 (p < 0.001). The other measures of severity, sleep satisfaction and quality of life supported the efficacy of rotigotine (p < 0.001 for pre-post-comparisons of all efficacy variables). The tolerability was described as “good” or “very good” by 80.3% of all patients. The most common adverse events were application site reactions (40.0%), which led to withdrawal in 13.2%. Further relatively frequent adverse events were nausea (9.5%) and fatigue (6.4%). Two drug-related serious adverse events, nausea and syncope, required hospitalization. Symptoms of augmentation were not reported by the patients.ConclusionRotigotine provided a stable, clinically relevant improvement in all efficacy measures throughout one year of maintenance therapy. The transdermal patch was safe and generally well tolerated by the majority of patients. Comparable to any transdermal therapy, application site reactions were the main treatment complication.     

Rating of daytime and nighttime symptoms in RLS: validation of the RLS-6 scale of restless legs syndrome/Willis–Ekbom disease

BackgroundThe International Restless Legs Scale (IRLS) is the most widely used of the scales rating the severity of restless legs syndrome/Willis–Ekbom disease (RLS/WED). It has been well validated and is the primary end point for most of the therapeutic and nontherapeutic studies of RLS/WED. It has excellent psychometric properties, although it does not capture the severity of RLS under a wide variety of circumstances and times of day. Moreover, the IRLS has a large placebo effect.MethodsThe Restless Legs Syndrome-6 Scale (RLS-6), however, takes another potentially valuable approach. Six items are rated on a 0–10 scale from no symptoms at 0 to very severe at 10. In addition to questions on satisfaction with sleep and sleepiness, the scale rates the severity of RLS for the past week under four separate circumstances: while falling asleep, during the night, during the day while sitting or lying, and during the day when moving around. The purpose of the current study is to report the validation of the RLS-6 under baseline and therapeutic conditions.ResultsThe RLS-6 seems to be an acceptable, reliable, precise, valid, and responsive instrument for the assessment of RLS severity in a specific and pragmatic manner.ConclusionsAt present, we view the RLS-6 not as a replacement for the IRLS but as a supplement, as each scale provides information not captured by the other.     

Randomized,placebo-controlled trial of ferric carboxymaltose in restless legs syndrome patients with iron deficiency anemia

ObjectiveIntravenous ferric carboxymaltose (FCM) has been shown to be efficacious in treating restless legs syndrome (RLS) symptoms in non-anemic patients. The aim of this study was to evaluate the effectiveness of FCM in treating RLS symptoms in patients who also had an iron deficiency anemia (IDA).MethodsThis is a randomized, double-blinded, placebo-controlled study. Subjects with RLS and IDA were enrolled. Subjects received an infusion of either 1500 mg FCM or placebo in Phase I. The primary outcomes were a change-from-baseline at week six on the International Restless Legs Syndrome Study Group scale (IRLS). Phase II of the study involved long-term (52 weeks) follow-up, for those who responded to treatment in the prior phase, with the potential for further treatment if symptoms returned.ResultsWe enrolled 29 RLS patients with IDA (15 FCM and 14 placebo). At week six post-infusion, FCM compared to placebo group showed significant improvement from baseline in IRLS score (−13.47 ± 7.38 vs. 1.36 ± 3.59). Among secondary outcome variables, quality of sleep showed significant improvement from baseline in the FCM group. 61% of subjects remained off RLS medications at the Phase II, week-52 endpoint. There were no serious adverse events observed in the study.ConclusionThe study showed significant efficacy and safety of FCM 1500 mg treatment both in the short term (6 weeks) and long term (52 weeks) in RLS patients with IDA.     

A phase II,open-label,non-comparative study of Botulinum toxin in Restless Legs Syndrome

ObjectiveTo assess the efficacy of intradermally injected botulinum neurotoxin type A (BoNT/A) in patients with Restless Legs Syndrome (RLS).MethodsWe conducted an optimal two-stage, phase II exploratory, open label, non-comparative clinical trial. The primary outcome measure was the efficacy of BoNT/A defined by the proportion of patients (responders) with ?50% improvement of their RLS severity score at week 2 following injections compared to baseline score at inclusion. Twenty-seven patients were to be included in the first stage of the trial, which was to be stopped if less than nine responders were documented. Selected patients had a minimum score of 21 on the International RLS Rating Scale. They all received a series of 20 intradermal injections of 0.05 ml of BoNT/A in symptomatic areas in their lower limbs. Change of RLS severity was evaluated over a 6 months period.ResultsOf the 27 selected patients, only six achieved the primary endpoint at week 2. In these six patients, the median duration (Inter-Quartile Range) of the IRLSRS score improvement of at least 50% was 46 days (42–126).ConclusionsConsidering the proportion of responders as the primary endpoint of this trial, BoNT/A showed no efficacy in alleviating RLS sensory symptoms.