Periodic Limb Movements (PLMs) during sleep in patients with Restless Legs Syndrome (RLS) have been shown to be associated with elevations in Blood Pressure (BP). Rotigotine has been shown to effectively reduce the incidence of PLMs in patients with RLS. The current study aims to demonstrate that treatment with Rotigotine could help reduce the number of nocturnal BP elevations associated with PLMs in patients with RLS.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
81
Rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.
Matching Placebo. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.
Unnamed facility
Berlin, Germany
Unnamed facility
Kassel, Germany
Unnamed facility
Marburg, Germany
Unnamed facility
München, Germany
Unnamed facility
Münster, Germany
Change From Baseline in the Number of Elevations of Systolic Blood Pressure (BP) During the Night That Are Associated With Periodic Limb Movements (PLMs) at the End of the 4-week Maintenance Period
Polysomnography (PSG) recordings, including the assessment of continuous Blood Pressure and 12-lead Electrocardiogram (ECG), were obtained on 2 consecutive nights prior to Baseline Visit and prior to End of Maintenance Period (Visit 7) for up to 8 hours per night. Readings from the first night of the PSG were only used for analysis if the PSG from the second night was determined to be not valid for evaluation. Influence of Periodic Limb Movements (PLMs) on sleep is reflected in the Periodic Limb Movement-Related Arousal Index (PLMAI). Arousal is defined as sudden change in the EEG activity and the index illustrates to what degree the PLMs contribute to arousal from sleep. Sleep stages and time spent in each sleep stage were determined from Electroencephalogram (EEG) readings. A negative value in Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.
Time frame: Baseline to the end of the 4-week Maintenance Period
Change From Baseline in the Total Number of Elevations of Systolic Blood Pressure (BP) During the Night at the End of the 4-week Maintenance Period
Polysomnography (PSG) recordings, including the assessment of continuous Blood Pressure and 12-lead Electrocardiogram (ECG), were obtained on 2 consecutive nights prior to Baseline Visit and prior to End of Maintenance Period (Visit 7) for up to 8 hours per night. Readings from the first night of the PSG were only used for analysis if the PSG from the second night was determined to be not valid for evaluation. Influence of Periodic Limb Movements (PLMs) on sleep is reflected in the Periodic Limb Movement-Related Arousal Index (PLMAI). Arousal is defined as sudden change in the EEG activity and the index illustrates to what degree the PLMs contribute to arousal from sleep. Sleep stages and time spent in each sleep stage were determined from Electroencephalogram (EEG) readings. A negative value in Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.
Time frame: Baseline to the end of the 4-week Maintenance Period
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Unnamed facility
Schwerin, Germany
Change From Baseline in the Periodic Limb Movements Index (PLMI) at the End of the 4-week Maintenance Period
The PLMI is defined as Periodic Limb Movements (PLMs)/ total time in bed in hours. PLMs are measured by Polysomnography (PSG). A negative value in PLMI Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.
Time frame: Baseline to the end of the 4-week Maintenance Period
Change From Baseline in the International Restless Legs Syndrome Rating Scale (IRLS) at the End of the 4-week Maintenance Period
The IRLS is a subject-based scale that consists of 10 items to evaluate the severity of major RLS symptoms and the impact of the disease on subjects' daytime functioning. Each of the 10 items is measured on a scale that ranges from 0 (not present) to 4 (severe). A sum score between 0 (no RLS symptoms present at all) and 40 (maximum severity in all symptoms) across all 10 items was calculated. A negative value in IRLS Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.
Time frame: Baseline to the end of the 4-week Maintenance Period
Change From Baseline in Restless Legs Syndrome-Quality of Life (RLS-QoL) at the End of the 4-week Maintenance Period
The RLS-QoL is a disease-specific instrument for the evaluation of Quality of life. It consists of 12 items and the overall sum score is calculated from all 12 items and measured on a scale that ranges from 0 (lowest Quality of life) to 60 (highest level of Quality of life). A negative value in RLS-QoL Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.
Time frame: Baseline to the end of the 4-week Maintenance Period
Clinical Global Impressions (CGI) Item 2 (Change of Condition) at the End of the 4-week Maintenance Period
The CGI Item 2 score measures any change in severity of RLS from Baseline on a 7-point scale consisting of the following categories: * 1- Very much improved * 2- Much improved * 3- Minimally improved * 4- No change * 5- Minimally worse * 6- Much worse * 7- Very much worse
Time frame: At the end of the 4-week Maintenance Period
Clinical Global Impressions (CGI) Item 1 (Severity of Illness) at the End of the 4-week Maintenance Period
The CGI Item 1 score measures the severity of illness on a 7-point scale consisting of the following categories: * 1- Normal, not ill at all * 2- Borderline ill * 3- Mildly ill * 4- Moderately ill * 5- Markedly ill * 6- Severely ill * 7- Among the most extremely ill subjects
Time frame: At the end of the 4-week Maintenance Period
Clinical Global Impressions (CGI) Item 3 (Therapeutic Efficacy) at the End of the 4-week Maintenance Period
The CGI Item 3 score measures the therapeutic efficacy on a 4-point scale consisting of the following categories: * 1- Very good * 2- Moderate * 3- Slight * 4- Unchanged or worse
Time frame: At the end of the 4-week Maintenance Period
Change From Baseline in Restless Legs Syndrome-6 Rating Scales (RLS-6) Item 1 at the End of the 4-week Maintenance Period
The RLS-6 consists of 6 items of which four items are designed to assess severity of RLS and two items cover sleep and daytime tiredness. Item 1 measures subject's satisfaction with sleep on a 11-point scale that ranges between 0 (completely satisfied) to 10 (completely dissatisfied). The ratings are given by the subjects. A negative value in RLS-6 Item 6 Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.
Time frame: Baseline to the end of the 4-week Maintenance Period
Change From Baseline in Restless Legs Syndrome-6 Rating Scales (RLS-6) Item 2 at the End of the 4-week Maintenance Period
The RLS-6 consists of 6 items of which four items are designed to assess severity of RLS and two items cover sleep and daytime tiredness. Item 2 measures the severity of RLS at time falling asleep on a 11-point scale that ranges between 0 (none) to 10 (very severe). The ratings are given by the subjects. A negative value in RLS-6 Item 2 Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.
Time frame: Baseline to the end of the 4-week Maintenance Period
Change From Baseline in Restless Legs Syndrome-6 Rating Scales (RLS-6) Item 3 at the End of the 4-week Maintenance Period
The RLS-6 consists of 6 items of which four items are designed to assess severity of RLS and two items cover sleep and daytime tiredness. Item 3 measures the severity of RLS during the night on a 11-point scale that ranges between 0 (none) to 10 (very severe). The ratings are given by the subjects. A negative value in RLS-6 Item 3 Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.
Time frame: Baseline to the end of the 4-week Maintenance Period
Change From Baseline in Restless Legs Syndrome-6 Rating Scales (RLS-6) Item 4 at the End of the 4-week Maintenance Period
The RLS-6 consists of 6 items of which four items are designed to assess severity of RLS and two items cover sleep and daytime tiredness. Item 4 measures the severity of RLS during day rest on a 11-point scale that ranges between 0 (none) to 10 (very severe). The ratings are given by the subjects. A negative value in RLS-6 Item 4 Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.
Time frame: Baseline to the end of the 4-week Maintenance Period
Change From Baseline in Restless Legs Syndrome-6 Rating Scales (RLS-6) Item 5 at the End of the 4-week Maintenance Period
The RLS-6 consists of 6 items of which four items are designed to assess severity of RLS and two items cover sleep and daytime tiredness. Item 5 measures the severity of RLS during day not rest on a 11-point scale that ranges between 0 (none) to 10 (very severe). The ratings are given by the subjects. A negative value in RLS-6 Item 5 Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.
Time frame: Baseline to the end of the 4-week Maintenance Period
Change From Baseline in Restless Legs Syndrome-6 Rating Scales (RLS-6) Item 6 at the End of the 4-week Maintenance Period
The RLS-6 consists of 6 items of which four items are designed to assess severity of RLS and two items cover sleep and daytime tiredness. Item 6 measures subject's tiredness or sleepiness during the day on a 11-point scale that ranges between 0 (not at all) to 10 (very severe). The ratings are given by the subjects. A negative value in RLS-6 Item 6 Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.
Time frame: Baseline to the end of the 4-week Maintenance Period