Effect of Rotigotine Patch Treatment on Cardiovascular Markers in Idiopathic Restless Legs Syndrome

NCT01823770 | Completed Phase 4 DMC

• 1 other identifier: 8917
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief 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. 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.

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

Outcome Measures

Primary Outcomes (1)

• 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).

  35 +/- 3 day

Secondary Outcomes (3)

• Digital pulse amplitude measured by reactive hyperhemia with finger plethysmographic methodology

  day 35 +/- 3

• PLMS and PLMS-microarousal indexes

  day 35 +/- 3

• Amplitude of PLMS-related HR responses

  day 35 +/- 3

Other Outcomes (6)

• change from baseline score of International RLS severity scale ((IRLS), RLSQoL, CGI)) at 35+/-3 days

  V0(Day -10± 3V1 (Day 0±3), V2(Day 14±3), V3(Day 21±3), V4(Day 35± 3)

• change from baseline "total sleep time" at 35 +/-3 days

  At the first visit (day 0) and the forth visit (day 35 +/- 3)

• change from baseline cytokine level at 35+/-3days

  At the first visit (day 0) and the forth visit (day 35 +/- 3)

Study Arms (3)

Rotigotine

ACTIVE COMPARATOR

Patients randomized to rotigotine who will be treated with rotigotine patchs

Drug: Rotigotine

Placebo

PLACEBO COMPARATOR

Patients randomized on the placebo group who will be treated with placebo patchs

Drug: Placebo patchs

Control group

NO INTERVENTION

Volunteers matched on sex, age and BMI with RLS patients who will not receive treatment(no treatment)

Interventions

Rotigotine DRUG

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).

Also known as: Rotigotine patchs

Rotigotine

Placebo patchs DRUG

Subject randomized on the placebo group will be treated with placebo patchs, following the same modalities and study periods that the rotigotine arm

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Subject has ferritin concentration of ≥50ng/mL at Screening.
• \. 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).
• \. 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.
• \. 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (1)

UH Montpellier

Montpellier, 34295, France

Location

MeSH Terms

Conditions

Restless Legs Syndrome; Cardiovascular Diseases

Interventions

rotigotine

Condition Hierarchy (Ancestors)

Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Parasomnias; Mental Disorders

Study Officials

• Yves Dauvilliers, PU PH

  UH Montpellier

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2013
• First Posted: April 4, 2013
• Study Start: November 26, 2012
• Primary Completion: July 4, 2016
• Study Completion: June 23, 2017
• Last Updated: May 15, 2018

Record last verified: 2018-05

Locations

FR (1)