ferric-carboxymaltose and Restless-Legs-Syndrome

Restless legs syndrome (RLS) is a common neurological disorder of unclear pathophysiology that appears to involve an iron deficiency in the brain. Some studies, but not others, suggest that intravenous injection of iron can reduce RLS severity.. The databases Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed were searched for randomized controlled trials, cohort studies and case-control studies of intravenous iron therapy to treat RLS. Eligible studies were meta-analyzed using Stata 12.0.. This analysis indicated that IV iron was more efficacious than placebo in treating RLS (OR: 4.71,95%CI 4.21-5.21,p < 0.0001). According to sub-group analysis, either IV ferric carboxymaltose (FCM) or iron sucrose was more efficacious than placebo in treating RLS. Adverse events did not differ significantly between patients receiving intravenous iron or placebo (OR 1.68, 95%CI 0.92-3.07, p = 0.093). The present study also indicated after accepting IV iron treatment the IRLS score in RLS patients decreased (OR = 6.75,95%CI 4.02-9.49, p < 0.0001). The subgroup analysis showed that IV iron dextran, iron sucrose, and FCM could alleviate the IRLS score.. The available evidence suggests that intravenous iron is effective and tolerable for patients with RLS regardless of peripheral iron status.

Topics: Ferric Compounds; Ferric Oxide, Saccharated; Humans; Injections, Intravenous; Iron-Dextran Complex; Maltose; Observational Studies as Topic; Randomized Controlled Trials as Topic; Restless Legs Syndrome

Brain iron status is fundamental in RLS pathogenesis. The aim of this study was to determine the clinical efficacy and brain iron concentration improvement in RLS patients with IDA, using 1500 mg FCM.. This is a randomized, double-blinded, placebo-controlled study. RLS patients with IDA were grouped into either 1500 mg FCM or placebo. The primary outcomes were the change from baseline on the International Restless Legs Syndrome Study Group scale (IRLS) and brain iron measured by QSM and R2∗.. A total of 18 RLS patients with IDA were enrolled, 10 in the FCM group and 8 in the placebo. At the week 6 endpoint, the FCM group showed significant improvement in both IRLS (-13.60 ± 9.47 vs. -3.63 ± 5.40, p = 0.011) and VAS (-40.50 ± 28.81 vs. -0.63 ± 28.28, p = 0.004) from baseline. Change from baseline with R2∗ techniques showed a treatment effect for the thalamus and QSM technique for both the substantia nigra and pulvinar. A correlation was proved between the IRLS difference and the difference of QSM in thalamus (p = 0.028).. This study demonstrates that 1500 mg FCM effectively treats RLS symptoms in IDA patients over six weeks, with MRI measurements of improved brain iron content serving as a potential biomarker for RLS patients.

Topics: Anemia, Iron-Deficiency; Brain; Ferric Compounds; Humans; Iron; Restless Legs Syndrome; Treatment Outcome

Intravenous 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).. This 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.. We 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.. The 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.

Topics: Anemia, Iron-Deficiency; Double-Blind Method; Ferric Compounds; Humans; Maltose; Restless Legs Syndrome; Treatment Outcome

Prospective, randomized, controlled, single-centre trial. (ClinicalTrials.gov: NCT01787526).. Tertiary care center in Graz, Austria.. 176 (138 female and 38 male) whole-blood and platelet apheresis donors aged ≥ 18 and ≤ 65 years with iron deficiency (ferritin ≤ 30ng/mL at the time of blood donation).. Intravenous iron (1 g ferric carboxymaltose, n = 86) or oral iron supplementation (10 g iron fumarate, 100 capsules, n = 90).. Clinical symptoms were evaluated by a survey before iron therapy (visit 0, V0) and after 8-12 weeks (visit 1, V1), including questions about symptoms of restless legs syndrome (RLS), chronic fatigue syndrome (CFS), sleeping disorders, quality of life and symptoms like headaches, dyspnoea, dizziness, palpitations, pica and trophic changes in fingernails or hair.. We found a significant improvement in the severity of symptoms for RLS, fatigue and sleep quality (. Iron supplementation in iron-deficient blood donors may be an effective strategy to improve symptoms related to iron deficiency and the wellbeing of blood donors.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anemia, Iron-Deficiency; Blood Donors; Dietary Supplements; Fatigue Syndrome, Chronic; Female; Ferric Compounds; Humans; Infusions, Intravenous; Iron, Dietary; Male; Maltose; Middle Aged; Quality of Life; Restless Legs Syndrome; Severity of Illness Index; Sleep Wake Disorders; Treatment Outcome; Young Adult

There have been four randomized, placebo-controlled, double-blinded studies of intravenous (IV) iron in Restless Legs Syndrome (RLS), all of which delivered a final total dose of 1000 mg of iron. The purpose of this study was to evaluate effects of a lesser total dose (500 mg of iron).. Subjects with idiopathic RLS were enrolled in a randomized, double-blinded, placebo-controlled study. Subjects received either 500 mg ferric carboxymaltose (FCM) or placebo as a single infusion (Phase I). Subjects who were previously on medication were off any RLS medications for at least two weeks prior to baseline assessment. The primary outcome variable was a change-from-baseline at week six on the International RLS Severity Scale (IRLSS) and a subject-completed Visual Analog Scale of Severity (VAS). Phase II of the study involved long-term (30 weeks) follow-up after completing the six week efficacy phase.. At week six post infusion, FCM, compared to placebo recipients, showed no significantly greater change-from-baseline for both primary outcome measures (IRLSS scale, FCM 500 mg vs. placebo: -8.3 ± 7.5 vs. -4.8 ± 8.7, p = 0.100; VAS, FCM 500 mg vs. placebo: -23.4 ± 24.1 vs. -13.3 ± 23.1, p = 0.077). None of the secondary outcome variables showed a significant difference at week six. Seven (21.9%) of the 32 subjects treated with iron in Phase I remained free from further RLS medications at 30 weeks. No serious adverse effects were found in this study.. This study did not show significant benefit from a single 500 mg FCM treatment for RLS symptoms. The two previous, well-controlled, trials of 1000 mg FCM showed significant treatment benefits which suggested that there may have been a clinically relevant total dose required to achieve a clinical response.

Topics: Administration, Intravenous; Double-Blind Method; Female; Ferric Compounds; Humans; Male; Maltose; Middle Aged; Restless Legs Syndrome; Severity of Illness Index; Treatment Outcome

Compromised iron status is important in restless legs syndrome pathophysiology. We compared the efficacy and tolerability of ferric carboxymaltose (single intravenous dose) versus placebo for restless legs syndrome treatment in iron-deficient nonanemic patients.. Patients with moderate to severe restless legs syndrome and serum ferritin < 75 μg/L (or serum ferritin 75-300 μg/L and transferrin saturation < 20%) were randomized to ferric carboxymaltose (1000 mg iron) or placebo. Mean change difference between ferric carboxymaltose and placebo in International Restless Legs Syndrome Severity Scale score from baseline to week 4 was the primary end point; week 12 was a secondary end point.. Ferric carboxymaltose treatment (n = 59) led to nonsignificant improvement over placebo (n = 51) in International Restless Legs Syndrome Severity Scale score at week 4 (difference [95% confidence interval], -2.5 [-5.93 to 1.02], P = 0.163), reaching significance by week 12 (-4.66 [-8.59 to -0.73], P = 0.021).. In patients who responded to treatment, ferric carboxymaltose may require more time to stabilize restless legs syndrome than previously assumed. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Topics: Aged; Aged, 80 and over; Female; Ferric Compounds; Ferritins; Hematinics; Humans; Iron Metabolism Disorders; Male; Maltose; Middle Aged; Prospective Studies; Restless Legs Syndrome; Single-Blind Method; Time Factors; Treatment Outcome

Intravenous (IV) iron has been used as a treatment to reduce Restless Legs Syndrome (RLS) symptoms, but two double-blinded trials of a frequently prescribed IV iron formulation, iron sucrose, failed to show lasting efficacy. This study evaluates efficacy and safety of a new IV iron formulation (ferric carboxymaltose, FCM) with molecular properties that may make iron more available for uptake to the brain than iron sucrose does.. In this 28-day, multi-centre, randomised, placebo-controlled trial 46 RLS patients were discontinued from all RLS treatment. Twenty-four received 500 mg FCM in two doses 5 days apart and 22 received a matching placebo. At day 28, those on placebo were given a single 1000 mg IV FCM and those not responding to initial treatment were given a third dose of 500 mg FCM. Patients were followed up for 24 weeks or until needing added RLS treatment.. FCM significantly improved primary and secondary outcomes compared to placebo: International Restless Legs Syndrome study group severity scale (IRLS) average (SD) decrease of 8.9 (8.52) versus 4.0 (6.11), p=0.040; Clinical Global Inventory of Change (CGI-1) very much or much improved 48.3% versus 14.3%, p=0.004. Quality of life was also significantly improved. Of the 24 with initial iron treatment 45% responded and 29% remitted (IRLS ≤ 10) at day 28, and 25% continued free of other RLS medications at 24 weeks after treatment. The single 1000 mg dose on day 28 produced the same degree of treatment response as the divided dose, but the added 500 mg dose for those not responding to the initial treatment showed little benefit. There were no significant adverse events.. IV FCM provided a safe and effective treatment for RLS that lasted for at least 24 weeks for some patients. Larger studies are needed to confirm these results.

Topics: Adult; Aged; Brain; Female; Ferric Compounds; Ferritins; Follow-Up Studies; Humans; Iron; Male; Maltose; Middle Aged; Pilot Projects; Placebos; Restless Legs Syndrome; Severity of Illness Index; Treatment Outcome

Restless sleep disorder has been described in the literature as a disorder affecting children and presenting with large muscle movements during sleep with an index of 5 events/h or more, leading to daytime impairment including sleepiness or behavioral problems. Children with restless sleep disorder have been found to have low ferritin levels. Studies with iron supplementation both oral or intravenous have been shown effective in clinically improving both nighttime and daytime symptoms. However objective data of the improvement is lacking. Repeating polysomnography is expensive, and alternative methods of assessing large muscle movements are needed. In this small case series we present actigraphy results in 3 children with restless sleep disorder collected for 1 week, a week before and 8 weeks after intravenous iron supplementation. Although actigraphy parameters were not highly consistent between our 3 patients, improvement in symptoms tend to parallel sleep parameters in actigraphy.. Chu ZYB, DelRosso LM, Mogavero MP, Ferri R. Actigraphy evaluation before and after intravenous ferric carboxymaltose in 3 children with restless sleep disorder.

Topics: Actigraphy; Child; Humans; Iron; Restless Legs Syndrome; Sleep; Sleep Wake Disorders

Restless legs syndrome (RLS) may be underdiagnosed in children with autism spectrum disorder (ASD) due to difficulty expressing the symptoms in their own words. In addition, administration of oral iron may be particularly difficult in children with ASD.. This was a retrospective, open-label case series of children with ASD, restless legs (RL) symptoms, and serum ferritin <30 μg/L, who either had failed or did not tolerate oral iron, and were subsequently treated with intravenous (IV) ferric carboxymaltose (FCM). Patients received a single dose of IV FCM, 15 mg/kg up to a maximum dose of 750 mg. Data collected pre- and eight weeks post-infusion included presenting symptoms, serum ferritin, iron profile, and Clinical Global Impression Scale (CGI-Severity pre- and CGI-Improvement post-infusion). Adverse effects were assessed.. Nineteen children, 4-11 years old (12 male, median age 6, interquartile range (IQR 4-11) were included. A definite RLS diagnosis was identified in 6 verbal children (31.6%). RL symptoms (designated probable RLS) in the 13 other children met all RLS diagnostic criteria except "improvement of symptoms with movement," which was not definitively determined. Baseline median values were: ferritin 10 μg/L (IQR 10-16), iron 66.5 μg/dL (IQR 57-96), TIBC 382 μg/dL (IQR 360-411) and transferrin saturation 19% (IQR 14-28). Median CGI-S was 4 (moderate symptoms) (IQR 3-4). At eight weeks after IV FCM, all measures were improved. Median ferritin was 68 μg/L (IQR 62.5-109, p < 0.00045). Median CGI-I was 1 (very much improved) (IQR 1-2). All children meeting definite RLS criteria improved. Three children in the probable RLS group did not improve. Children meeting the full RLS criteria had lower baseline ferritin levels than those with a probable diagnosis (9 μg/L, IQR 9-10 vs. 13 μg/L, IQR 10-16, Mann-Whitney test p < 0.045). Adverse effects included lightheadedness, gastrointestinal discomfort, fever, and headache among others.. The majority of children (84.2%) with ASD, restless legs symptoms, and serum ferritin <30 μg/L had clinical improvement and significantly better serum iron parameters after a single IV FCM infusion. Although larger, randomized trials are needed, IV FCM appears to be a promising treatment for this subset of children with ASD.

Topics: Autism Spectrum Disorder; Child; Child, Preschool; Female; Ferric Compounds; Ferritins; Humans; Iron; Male; Restless Legs Syndrome; Retrospective Studies; Treatment Outcome

Iron supplementation is the most commonly considered treatment option for children with restless legs syndrome (RLS) or periodic limb movement disorder (PLMD); however, there is a scarcity of evidence on the effectiveness of intravenous preparations. In this study, we evaluated the effectiveness and tolerability of intravenous ferric carboxymaltose (IV FCM) on clinical symptoms and iron indices in children with RLS or PLMD.. This was a single-center retrospective data analysis. Children with a diagnosis of RLS or PLMD, who underwent a single infusion of IV FCM, were included. Clinical Global Impression (CGI) Scale scores, serum ferritin, and serum iron profile at baseline and after eight weeks post infusion were obtained. Adverse effects were assessed.. Thirty-nine children received IV FCM, 29 with RLS and 10 with PLMD. Pre-infusion CGI-Severity revealed moderate illness, with post-infusion CGI-Improvement between "very much improved" and "much improved". Ferritin increased from 14.6 μg/L±7.01 to 112.4 μg/L±65.86 (p < 0.00001), together with improvements in iron, total iron binding capacity, and transferrin levels from baseline to post-treatment. When compared to children with RLS, those with PLMD had a similar improvement in clinical symptoms and laboratory parameters. Seven subjects (14.3%) experienced one or two adverse events; all were mild.. Children with RLS and PLMD responded to IV iron supplementation with improvement in both clinical severity and laboratory parameters. Treatment was well tolerated. Although larger, randomized-controlled trials are needed, IV FCM appears to be a promising alternative to oral iron supplementation for the treatment of pediatric RLS or PLMD.

Topics: Child; Ferric Compounds; Humans; Maltose; Nocturnal Myoclonus Syndrome; Restless Legs Syndrome; Retrospective Studies; Treatment Outcome

Significant benefit of intravenous ferric carboxymaltose (FCM) treatment for restless legs syndrome (RLS) has been well-established. However, no clinical indicators predicting treatment response of RLS have been established. This study aimed to determine factors predicting outcome of clinical FCM treatment of RLS patients.. Data were retrospectively reviewed from all patients who received FCM treatment for RLS from April 2016 to April 2019. These data included: detailed history, international RLS scale score (IRLS), questionnaires, comorbidity, and previous RLS medication use. Morning fasting serum iron, ferritin, and total iron-binding capacity were measured before and at four weeks after treatment. RLS patients with possible secondary RLS were identified by reviewing the medical histories. This included patients with iron deficiency anemia, lumbosacral radiculopathy, and gastrectomy. Primary RLS included those with no indication of secondary medical factors contributing to RLS. Treatment response was assessed using the IRLS and clinical ratings at four weeks after FCM administration. Patients with a greater than 40% decrease in IRLS were classified as responders.. The study comprised 164 patients with IRLS and clinical ratings obtained before and at four weeks after intravenous (IV) iron. Treatment responses differed considerably between diagnostic groups of RLS. Percentage responding was: 64.7% (66 of 102) for patients with primary RLS, 90.9% (10 of 11) with gastrectomy, 91.3% (21 of 23) with iron deficiency anemia and 39.3% (11 of 28) with lumbosacral radiculopathy. When responders were compared to non-responders in primary RLS patients, responders had significantly lower serum iron (80.5 ± 26.7 vs. 95.8 ± 30.5 μg/dL, p = 0.022) and percentage transferrin saturation (%TSAT) (25.4 ± 9.6 vs. 30.5 ± 10.5%, p = 0.026) in females, but not males. Logistic regression controlling for major subject variables showed that %TSAT significantly predicted response. (odds ratio [OR]: 0.955, confidence interval: 0.913-0.998, p = 0.040).. Intravenous FCM in moderate to severe RLS patients is beneficial as a first-line or add-on treatment, particularly for patients with compromised peripheral iron state. Overall, lower %TSAT predicted better chance of responding to the IV iron treatment especially for females.

Topics: Anemia, Iron-Deficiency; Female; Ferric Compounds; Humans; Maltose; Restless Legs Syndrome; Retrospective Studies; Treatment Outcome

There have been three randomized, placebo-controlled, double-blind studies of intravenous iron in restless legs syndrome (RLS), with differing outcomes. The one positive study used ferric carboxymaltose (FCM) at a total dose of 1000 mg. The purpose of this study was to replicate and extend the findings from the prior FCM study.. Non-anemic, idiopathic RLS patients were enrolled in a randomized, double-blinded, placebo-controlled study and received either 1000 mg FCM or placebo as a single infusion (phase I). Subjects were off any RLS medications for at least two weeks prior to baseline assessment. The primary outcome variable was change from baseline at week 6 on the International Restless Legs Syndrome Severity (IRLSS) scale and a subject-completed, visual analog scale (VAS) of severity. Phase II of the study involved long-term (30 weeks) follow-up after completion of the six-week efficacy phase.. At week 6 postinfusion, FCM compared to placebo recipients showed significantly greater change from baseline for both primary outcome measures (IRLSS scale, -11.9 ± 8.04 vs -7.88 ± 5.89, p = 0.03; VAS, -40.6 ± 22.7 vs -21.3 ± 20.0, p = 0.001). None of the secondary outcome variables showed a significant difference at week 6. After six weeks of treatment, the FCM group had 19 (59.4%) responders, of which 12 had IRLSS scores <10 ("remitters"). Twelve (37.5%) of the 32 subjects treated with iron in phase I remained free of further RLS medications at 30 weeks. There were no serious adverse events observed in this study.. Two studies now support the value of FCM treatment both in the short term (six weeks) and long term (30 weeks) for improving RLS symptoms.

Topics: Administration, Intravenous; Adult; Asian People; Double-Blind Method; Female; Ferric Compounds; Humans; Iron; Male; Maltose; Middle Aged; Randomized Controlled Trials as Topic; Restless Legs Syndrome; Trace Elements; Treatment Outcome

The objective of this study was to test the efficacy and safety of intravenous ferric carboxymaltose (FCM) in pregnant women with restless legs syndrome (RLS) and iron deficiency or anemia. The open-label pilot study (exploratory) was performed at the University Hospital of Zürich and the Neurocenter of Southern Switzerland (Lugano).. Nineteen women in the third trimester of pregnancy with moderate-to-severe RLS and serum ferritin levels <35 µg/l or hemoglobin (Hb) < 11.0 g/dl were included in the study. RLS was graded according to the International Restless Legs Syndrome (IRLS) Study Group rating scale. All participants had a score of ≥20 or had RLS ≥3 times/week. Based on the Hb levels, 500 or 700 mg of FCM was administered over 20 min. The primary end point was a ≥ 50% reduction in the mean IRLS score one week after FCM infusion. The secondary end points included periodic limb movements (PLMs; assessed using nocturnal foot actigraphy), sleep quality (assessed using the Pittsburgh Sleep Quality Index), and safety.. The IRLS score decreased from 23 ± 7 (baseline) to 13 ± 7 (P <0.01), whereas the PLM index decreased from 35 ± 26 (baseline) to 25 ± 20 (P <0.001). Significant improvement in sleep quality was also reported (P <0.029), and treatment was well tolerated. Three serious adverse events were reported, but they were considered unrelated to treatment.. These data provide promising evidence on the safety and efficacy of FCM for moderate-to-severe RLS in pregnant women with iron deficiency or anemia. Therefore, a future placebo-controlled study is warranted.

Topics: Administration, Intravenous; Adult; Anemia, Iron-Deficiency; Double-Blind Method; Female; Ferric Compounds; Ferritins; Humans; Maltose; Pilot Projects; Pregnancy; Pregnancy Complications; Prospective Studies; Restless Legs Syndrome; Switzerland; Time Factors; Treatment Outcome

To 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.. Twenty 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.. Twelve 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.. FCM 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.

Topics: Adult; Aged; Comorbidity; Female; Ferric Compounds; Ferritins; Humans; Injections, Intravenous; Iron; Iron Deficiencies; Male; Maltose; Middle Aged; Prospective Studies; Restless Legs Syndrome; Severity of Illness Index; Treatment Outcome