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Restless Legs SyndromePhase 4ENCORENCT01455012

Effects of Neupro on Cardiovascular Observations in Patients With Restless Legs Syndrome

A Phase 4 study testing Rotigotine in people with Restless Legs Syndrome, run by UCB BIOSCIENCES GmbH at 6 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Restless Legs Syndrome
What is being tested?
Rotigotine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
81 participants
Where
6 sitesGermany
Study dates
Sep 2011to Jun 2012
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject is informed and given ample time and opportunity to think about her/his participation and give her/his written informed consent
  • Subject understands the investigational nature of the study and is willing and able to comply with the study requirements. Subject is willing to accept that he/she might be treated with placebo during the Treatment Period
  • Subject is able to apply/remove the study patch correctly
  • Subject is male or female, and is ≥18 and ≤75 years of age
  • Subject meets the diagnosis of idiopathic Restless Legs Syndrome (RLS) based on the 4 essential clinical features according to the International Restless Legs Syndrome Study Group (Allen et al,2003): 1. An urge to move legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs (The urge to move can be present without uncomfortable sensations. Arms or other body parts can also be affected) 2. The urge to move or unpleasant sensations begin or worsen during periods of rest or inactivity, such as lying or sitting 3. The urge to move or unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues 4. The urge to move or unpleasant sensations are worse in the evening or night than during the day or only occur in the evening or night (When symptoms are very severe, the worsening at night may not be noticeable but must have been previously present)
  • Subject has a score of ≥11 on the RLS-Diagnostic Index (RLS-DI) (Benes and Kohnen, 2009)
Show all 12Show fewer
  • Subject has an initial response to previous dopaminergic treatment for RLS or has no previous dopaminergic treatment (ie, de novo)
  • The subject's Body Mass Index (BMI) is ≥18 kg/m^2 and ≤35 kg/m^2
  • At Baseline subject has a score of ≥15 on the IRLS (indicating moderate to severe RLS)
  • At Baseline subject has a score of ≥4 points on the CGI Item 1 assessment (indicating moderately ill)
  • At Baseline subject has a score of ≥15 PLM/h on the Periodic Limb Movements Index (PLMI) based on polysomnography (PSG) (recorded during the second night) as assessed by the investigator
  • Subjects are on a concomitant dose of antihypertensives that is at a stable dose for at least 4 weeks prior to Baseline and hypertension is reasonably controlled while the subject agrees to continue at this dose for the duration of the study, or subject has not received concomitant treatment with antihypertensives for at least 4 weeks prior to Baseline and does not intend to start such use during the study

Who cannot join

  • Subject has RLS due to renal insufficiency (uremia), iron deficiency anemia, or rheumatoid arthritis
  • Subject has RLS associated with previous or concomitant therapy with dopamine D2 receptor antagonists, butyrophenones, metoclopramide, atypical antipsychotics (eg, olanzapine), tri- and tetra-cyclic antidepressants, mianserine, or lithium or H2-blockers (eg, cimetidine), or due to withdrawal from drugs such as anticonvulsants, benzodiazepines, barbiturates, and other hypnotics
  • Subject has a history of sleep disturbances, such as sleep apnea syndrome (including obstructive sleep apnea), narcolepsy, sleep attacks/sudden onset of sleep, or myoclonus epilepsy either observed during PSG (local PSG evaluations) or evidenced by subject history
  • Subject has uncontrolled hypertension according to the judgment of the investigator
  • Subject has additional clinically relevant concomitant diseases, such as attention deficit hyperactivity disorder, polyneuropathy, akathisia, claudication, varicosis, muscle fasciculation, painful legs and moving toes, or radiculopathy
  • Subject has other central nervous system diseases, such as Parkinson's disease, dementia, progressive supranuclear paresis, multisystem atrophy, Huntington's chorea, amyotrophic lateral sclerosis, or Alzheimer's disease.
Show all 22Show fewer
  • Subject has a prior history of psychotic episodes
  • Subject has a history of chronic alcohol or drug abuse within the previous 12 months
  • Subject has any medical or psychiatric condition, which in the opinion of the investigator, can jeopardize or would compromise the subject's ability to participate in this study
  • Subject has clinically relevant cardiac dysfunction and/or arrhythmias (eg, suspected conduction system dysregulations, second or third degree atrioventricular block, complete left or right bundle branch block, sick sinus syndrome, New York Heart Association Class III or IV congestive heart failure, or had a myocardial infarction within 12 months prior to Screening [Visit 1])
  • Subject has clinically relevant venous or arterial peripheral vascular disease
  • Subject has a malignant neoplastic disease requiring therapy within 12 months prior to Screening (Visit 1)
  • Subject is currently receiving treatment with any of the following drug classes: neuroleptics, hypnotics, antidepressants, anxiolytic drugs, anticonvulsive therapy, budipine, dopamine antagonist antiemetics (except domperidone), opioids, benzodiazepines, monoamine oxidase (MAO) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, sedative antihistamines, psychostimulates, or amphetamines. If subject has received such therapy, a Washout Period of at least 7 days prior to Baseline (Visit 2) is required before starting treatment in this study
  • Subject is pregnant, nursing, or is a woman of childbearing potential who is not surgically sterile, 2 years postmenopausal, or does not consistently use 2 combined effective methods of contraception, including at least 1 barrier method, unless sexually abstinent
  • Subject is a shift worker or performs other continuous non-disease-related life conditions which do not allow regular sleep at night
  • At Screening Visit or Baseline Visit subject has symptomatic orthostatic hypotension
  • Subject is treated with dopamine agonists within a period of 14 days prior to Baseline or L-dopa within 7 days prior to Baseline
  • Subject has a medical history indicating intolerability to prior dopaminergic therapy (if pretreated)
  • Subject has received previous treatment with Rotigotine
  • Subject has participated in another study of an investigational drug or device within the 28 days prior to Visit 2 (Baseline) or is currently participating in another study of an investigational drug
  • Subject has a known hypersensitivity to any of the components of the study medication, such as a history of significant skin hypersensitivity to adhesives, known hypersensitivity to other transdermal medications, or has unresolved contact dermatitis
  • Subject has a lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response ("Yes") to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening (Visit 1)

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

Germany6 sites

  • Study site

    Berlin

  • Study site

    Kassel

  • Study site

    Marburg

  • Study site

    München

  • Study site

    Münster

  • Study site

    Schwerin

Other trials in Germany

About this study

Official title: Multicenter, Double-Blind, Placebo-Controlled, Two-Arm, Randomized, Parallel, Treatment Intervention, Sleep Lab Phase 4 Study to Assess the Effect of Rotigotine on Nocturnal Blood Pressure in Patients With Idiopathic Restless Legs Syndrome

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.

Being tested
Rotigotine, Placebo
Keywords
Rotigotine, Neupro, RLS, Cardiovascular Risk, Nocturnal Blood Pressure
Medical subject headings
Restless Legs Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RotigotineDrug

    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.

  • PlaceboDrug

    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.

Study groups in NCT01455012
Study groupRoleWhat they receive
RotigotineExperimentalRotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h)
Receives: Drug: Rotigotine
PlaceboPlacebo comparatorPlacebo
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline to the end of the 4-week Maintenance Period

Secondary outcomes (13)

  1. 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.

    Measured: Baseline to the end of the 4-week Maintenance Period

  2. 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.

    Measured: Baseline to the end of the 4-week Maintenance Period

  3. 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.

    Measured: Baseline to the end of the 4-week Maintenance Period

  4. 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.

    Measured: Baseline to the end of the 4-week Maintenance Period

  5. 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

    Measured: At the end of the 4-week Maintenance Period

  6. 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

    Measured: At the end of the 4-week Maintenance Period

  7. 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

    Measured: At the end of the 4-week Maintenance Period

  8. 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.

    Measured: Baseline to the end of the 4-week Maintenance Period

  9. 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.

    Measured: Baseline to the end of the 4-week Maintenance Period

  10. 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.

    Measured: Baseline to the end of the 4-week Maintenance Period

  11. 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.

    Measured: Baseline to the end of the 4-week Maintenance Period

  12. 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.

    Measured: Baseline to the end of the 4-week Maintenance Period

  13. 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.

    Measured: Baseline to the end of the 4-week Maintenance Period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Oct 2011 (estimated)
  2. Study startSep 2011
  3. Primary completionMay 2012
  4. Study completionJun 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
81 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01455012
Sponsor's protocol ID
SP0977
Other IDs
2011-000053-23
Acronym
ENCORE
Status last verified
Jul 2013
First submitted
10 Oct 2011
Last updated
26 Jul 2013
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Rotigotine in people with Restless Legs Syndrome, run by UCB BIOSCIENCES GmbH at 6 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jul 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Baseline to the end of the 4-week Maintenance Period). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01455012.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2013.

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