Restless Legs Syndrome (RLS)Phase 4NCT01823770
Effect of Rotigotine Patch Treatment on Cardiovascular Markers in Idiopathic Restless Legs Syndrome
A Phase 4 study testing Rotigotine in people with Restless Legs Syndrome (RLS), run by University Hospital, Montpellier at 1 site in France.
Trial summary
Several studies report association between restless legs syndrome (RLS), HTA and cardiovascular diseases . The mechanisms involved in this relationship remained unknown, but several evidences favor the role of periodic limb movements in sleep (PLMS), patterns frequently associated with RLS. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Restless Legs Syndrome (RLS)
- What is being tested?
- Rotigotine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 130 participants
- Where
- 1 siteFrance
- Study dates
- 26 Nov 2012to 23 Jun 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- To be eligible to participate in this study, all of the following criteria must be present in the patients:
- Subject is informed and given ample time and opportunity to think about her/his participation and has given 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 patches correctly.
- Subject is male or female, and is ≥18 and ≤80 years of age.
- Subject has a body mass index (BMI) of ≥18kg/m2 and ≤35kg/m2.
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- Subject has ferritin concentration of ≥50ng/mL at Screening.
- 9. Subject has a diagnosis of RLS based on the 4 cardinal diagnostic clinical features according to the International Restless Legs Syndrome Study Group 11. At Baseline, subject has a score of ≥15 points on the IRLS (indicating moderateto severe RLS).
- 12. At Baseline, subject scores ≥10 PLMs per hour on the PLMI based on PSG
- To be eligible to participate in this study, all of the following criteria must be present in the controls:
- Subject is informed and given ample time and opportunity to think about her/his participation and has given her/his written informed consent.
- Subject understands the investigational nature of the study and is willing and able to comply with the study requirements.
- 4. Subject is male or female, and is ≥18 and ≤80 years of age. 5. Subject has a body mass index (BMI) of ≥18kg/m2 and ≤35kg/m2.
Who cannot join
- RLS patients are not permitted to be included in the study if any of the following criteria is met:
- Subject has RLS associated with previous or concomitant therapy with dopamine D2 receptor antagonists, butyrophenones, metoclopramide, atypical antipsychotics (eg, olanzapine), antidepressants, mianserine, or lithium or H2-blockers (eg, cimetidine).
- Subject has a history of any sleep disorder other than RLS including a severe obstructive sleep apnea syndrome (Apnea hypopnea index > 30/h) not treated by a controlled Continuous Positive Airway Therapy (CPAP) for at least 1 month prior to Screening, or has narcolepsy or other hypersomnia.
- Subject has clinically relevant polyneuropathy which cannot be clearly differentiated from RLS symptoms in the opinion of the investigator.
- Subject has additional clinically relevant concomitant diseases, such as attention deficit hyperactivity disorder, painful legs, and moving toes.
- 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.
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- Subject has evidence of an impulse control disorder (Visit 1) as assessed by the Minnesota Impulsive Disorders Interview. If a subject has 1 or more positive modules on the mMIDI, he/she must be referred for a structured clinical interview, such as the Structured Clinical Interview for DSM-IV Axis 2 Personality Disorders (SCID-II) or another applicable structured interview for the diagnosis of ICDs.
- 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.
- Subject has a prior history of psychotic episodes.
- Subject has a history of chronic alcohol or drug abuse within the prior 12 months.
- Subject has any medical or psychiatric condition which in the opinion of the investigator, can jeopardize or compromise the subject's wellbeing or ability to participate in this study.
- Subject has a history of symptomatic (not asymptomatic) orthostatic hypotension in the 6 months prior to Baseline
- Subject has clinically relevant cardiovascular disease which, in the opinion of the investigator, can compromise the subject's wellbeing or ability to participate in this study.
- 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 (zolpidem and zopiclone may be considered as rescue medication in case of inability to sleep), monoamine oxidase (MAO) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, sedative antihistamines, psychostimulants, or amphetamines. If subject has received such therapy, a Washout Period of at least 7 days prior to Baseline 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 pursues shift work or performs other continuous non-disease-related life conditions which do not allow regular sleep at night.
- Subject has had previous treatment 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 dopaminergic therapy (if pretreated) or has experienced augmentation when previously treated with any dopaminergic agent.
- Subject has participated in another study of an investigational drug within the 28 days prior to 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.
- Subjects unable or unwilling to undergo informed consent
- Subject with no rights from the national health insurance programme
- Subject has a medical history indicating intolerability to rotigotine or inefficiency (previously treated).
- subjects who is performed an IRM examen during the study duration.
- Normal controls are not permitted to enroll in the study if any of the following criteria is present:
- Subject has a diagnosis of RLS based on the 4 cardinal diagnostic clinical features according to the International Restless Legs Syndrome Study Group
- At Baseline, subject scores ≥10 PLMs per hour on the PLM index based on PSG
- Subject has a history of any sleep disorder including a severe obstructive sleep apnea syndrome (Apnea hypopnea index > 30/h) not treated by a controlled Continuous Positive Airway Therapy (CPAP) for at least 1 month prior to Screening, or has narcolepsy or other hypersomnia.
- Subject has clinically relevant polyneuropathy, attention deficit hyperactivity disorder, Parkinsonian syndrome or dementia
- 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, or history of psychotic episodes, or history of chronic alcohol or drug abuse within the prior 12 months.
- Subject has clinically relevant cardiovascular disease which, in the opinion of the investigator, can compromise the subject's wellbeing or ability to participate in this study.
- Subject is currently receiving treatment with any of the following drug classes: dopaminergic agonists, neuroleptics, hypnotics, antidepressants, anxiolytic drugs, anticonvulsive therapy, budipine, dopamine antagonist antiemetics (except domperidone), opioids, benzodiazepines (zolpidem and zopiclone may be considered as rescue medication in case of inability to sleep), monoamine oxidase (MAO) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, sedative antihistamines, psychostimulants, or amphetamines.
- 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 pursues shift work or performs other continuous non-disease-related life conditions which do not allow regular sleep at night.
- Subject has participated in another study of an investigational drug within the 28 days prior to Baseline or is currently participating in another study of an investigational drug
- Subjects unable or unwilling to undergo informed consent
- Subject with no rights from the national health insurance programme
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Rotigotine Patch Treatment on Cardiovascular Markers in Idiopathic Restless Legs Syndrome : a Pilot Randomized, Placebo-controlled Study
Several studies report association between restless legs syndrome (RLS), HTA and cardiovascular diseases .
The mechanisms involved in this relationship remained unknown, but several evidences favor the role of periodic limb movements in sleep (PLMS), patterns frequently associated with RLS. Sympathetic overactivity is associated with PLMS with increased pulse rate and blood pressure coincident with PLMS. PLMS-related repetitive nocturnal blood pressure fluctuations could contribute to the risk of high blood pressure, heart disease, and stroke in patients with RLS, especially in the elderly. Several studies already reported that dopaminergic agonists reduce the severity of RLS and the PLMS index.
Read more
Do dopaminergic agonists reduce the risk of cardiovascular diseases and associated autonomic dysfunctions in patients with RLS ?
Nocturnal BP (blood pressure) decline has major clinical implications, and the loss of normal reduction in BP during sleep is associated with high risk of cardiovascular morbidity and mortality.
The main aim of this study was to evaluate the impact of rotigotine patch treatment on validated cardiovascular risk factors ambulatory BP during night, day and night-to-day ratio, and endothelial function in patients with idiopathic RLS compared to placebo.
- Conditions
- Restless Legs Syndrome (RLS)
- Being tested
- Rotigotine, Placebo patchs
- Keywords
- Restless Legs Syndrome (RLS), Rotigotine, HTA, Cardiovascular diseases, Periodic Limb Movements in Sleep (PLMS), dopaminergic agonist, Sympathetic overactivity, blood pressure
- Medical subject headings
- Restless Legs Syndrome, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RotigotineDrug
Also called Rotigotine patchs
Subjects randomized to rotigotine will start treatment with a rotigotine dose of 1mg/24h for 1 week. The dose can be increased weekly until either the optimal or the maximal dose of 3mg/24h has been reached. Subjects will maintain the optimal/maximal dose during the 2-week Maintenance Period. Following the Maintenance Period, subjects will be de-escalated from their optimal dose by decreasing the dose by 1mg/24h every other day until complete withdrawal (Taper period).
Placebo patchsDrug
Subject randomized on the placebo group will be treated with placebo patchs, following the same modalities and study periods that the rotigotine arm
| Study group | Role | What they receive |
|---|---|---|
| Rotigotine | Active comparator | Patients randomized to rotigotine who will be treated with rotigotine patchs Receives: Drug: Rotigotine |
| Placebo | Placebo comparator | Patients randomized on the placebo group who will be treated with placebo patchs Receives: Drug: Placebo patchs |
| Control group | No intervention | Volunteers matched on sex, age and BMI with RLS patients who will not receive treatment(no treatment) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentages of non-dippers(defined as <10% drop in BP during sleep)at 35+/-3 days
Percentages of non-dippers is defined as <10% drop in blood pressure (BP) during sleep (24h ambulatory BP monitoring).
Measured: 35 +/- 3 day
Secondary outcomes (3)
Digital pulse amplitude measured by reactive hyperhemia with finger plethysmographic methodology
Fasting morning peripheral arterial tonometry (PAT)
Measured: day 35 +/- 3
PLMS and PLMS-microarousal indexes
Nocturnal polysomnography (PSG)
Measured: day 35 +/- 3
Amplitude of PLMS-related HR responses
Nocturnal polysomnography (PSG)
Measured: day 35 +/- 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2013 (estimated)
- Study start26 Nov 2012
- Primary completion4 Jul 2016
- Study completion23 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Restless Legs Syndrome (RLS)Studies of the same condition, open and under way.
- More trials run by University Hospital, MontpellierThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yves Dauvilliers, PU PH, Principal investigator, UH Montpellier
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01823770
- Sponsor's protocol ID
- 8917
- Status last verified
- May 2018
- First submitted
- 22 Mar 2013
- Last updated
- 15 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Rotigotine Patch Treatment on Cardiovascular Markers in Idiopathic Restless Legs Syndrome : a Pilot Randomized, Placebo-controlled Study
- ClinicalTrials.gov ID
- NCT01823770
- Acronym / sponsor ID
- 8917
- Conditions
- Restless Legs Syndrome (RLS)
- Keywords
- Restless Legs Syndrome (RLS), Rotigotine, HTA, Cardiovascular diseases, Periodic Limb Movements in Sleep (PLMS), dopaminergic agonist, Sympathetic overactivity, blood pressure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Study start
- 26 Nov 2012 (actual)
- Primary completion
- 4 Jul 2016 (actual)
- Study completion
- 23 Jun 2017 (actual)
- First posted
- 4 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Several studies report association between restless legs syndrome (RLS), HTA and cardiovascular diseases .
The mechanisms involved in this relationship remained unknown, but several evidences favor the role of periodic limb movements in sleep (PLMS), patterns frequently associated with RLS. Sympathetic overactivity is associated with PLMS with increased pulse rate and blood pressure coincident with PLMS. PLMS-related repetitive nocturnal blood pressure fluctuations could contribute to the risk of high blood pressure, heart disease, and stroke in patients with RLS, especially in the elderly. Several studies already reported that dopaminergic agonists reduce the severity of RLS and the PLMS index.
Do dopaminergic agonists reduce the risk of cardiovascular diseases and associated autonomic dysfunctions in patients with RLS ?
Nocturnal BP (blood pressure) decline has major clinical implications, and the loss of normal reduction in BP during sleep is associated with high risk of cardiovascular morbidity and mortality.
The main aim of this study was to evaluate the impact of rotigotine patch treatment on validated cardiovascular risk factors ambulatory BP during night, day and night-to-day ratio, and endothelial function in patients with idiopathic RLS compared to placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Rotigotine | Active comparator | Drug: RotigotinePatients randomized to rotigotine who will be treated with rotigotine patchs |
| Placebo | Placebo comparator | Drug: Placebo patchsPatients randomized on the placebo group who will be treated with placebo patchs |
| Control group | No intervention | –Volunteers matched on sex, age and BMI with RLS patients who will not receive treatment(no treatment) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- To be eligible to participate in this study, all of the following criteria must be present in the patients:
- 9. Subject has a diagnosis of RLS based on the 4 cardinal diagnostic clinical features according to the International Restless Legs Syndrome Study Group 11. At Baseline, subject has a score of ≥15 points on the IRLS (indicating moderateto severe RLS).
- 12. At Baseline, subject scores ≥10 PLMs per hour on the PLMI based on PSG
- To be eligible to participate in this study, all of the following criteria must be present in the controls:
- 4. Subject is male or female, and is ≥18 and ≤80 years of age. 5. Subject has a body mass index (BMI) of ≥18kg/m2 and ≤35kg/m2.
Key exclusion criteria (39 listed)
- RLS patients are not permitted to be included in the study if any of the following criteria is met:
- Normal controls are not permitted to enroll in the study if any of the following criteria is present:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RotigotineAlso: Rotigotine patchsSubjects randomized to rotigotine will start treatment with a rotigotine dose of 1mg/24h for 1 week. The dose can be increased weekly until either the optimal or the maximal dose of 3mg/24h has been reached. Subjects will maintain the optimal/maximal dose during the 2-week Maintenance Period. Following the Maintenance Period, subjects will be de-escalated from their optimal dose by decreasing the dose by 1mg/24h every other day until complete withdrawal (Taper period). | Drug | Rotigotine |
| Placebo patchsSubject randomized on the placebo group will be treated with placebo patchs, following the same modalities and study periods that the rotigotine arm | Drug | Placebo |
Primary outcome
Percentages of non-dippers(defined as <10% drop in BP during sleep)at 35+/-3 days
Time frame: 35 +/- 3 day
Percentages of non-dippers is defined as <10% drop in blood pressure (BP) during sleep (24h ambulatory BP monitoring).
3 secondary outcomes
Digital pulse amplitude measured by reactive hyperhemia with finger plethysmographic methodology
Time frame: day 35 +/- 3
PLMS and PLMS-microarousal indexes
Time frame: day 35 +/- 3
Amplitude of PLMS-related HR responses
Time frame: day 35 +/- 3
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yves Dauvilliers, PU PH principal investigator
UH Montpellier
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rotigotine in people with Restless Legs Syndrome (RLS), run by University Hospital, Montpellier at 1 site in France.
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 13 inclusion and 39 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 15 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Percentages of non-dippers(defined as <10% drop in BP during sleep)at 35+/-3 days (time frame: 35 +/- 3 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 May 2018.