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出境医 / 临床实验 / Effect of Safinamide on Sleep Quality in Patients With Parkinson's Disease

Effect of Safinamide on Sleep Quality in Patients With Parkinson's Disease

Study Description
Brief Summary:
Patients suffering of Parkinson's Disease will be treated with 50 mg/day of Safinamide per os for 2 weeks (escalation phase). Then, safinamide will be increased up to 100 mg/day and, if tolerated, the treatment will be taken for 10 more weeks (maintenance phase). Total treatment 12 weeks.

Condition or disease Intervention/treatment Phase
Idiopathic Parkinson's Disease (at Later Stage) Drug: Safinamide Phase 4

Detailed Description:

Adult patients affected by PD and suffering from motor fluctuations will be screened for participation.

If the inclusion and exclusion criteria are met, the participant will enter in the baseline assessment phase and undergo 1 night baseline PSG and 1 week baseline actigraphy. The patient will then start the treatment with 50 mg/day of Safinamide per os for 2 weeks (escalation phase). Then, safinamide will be increased up to 100 mg/day and, if tolerated, the treatment will last for 10 weeks (maintenance phase). At week 12 (end of treatment), the questionnaires, actigraphy and PSG will be repeated. A safety follow-up visit is scheduled 4 weeks after study treatment completion.

The treatment will be continued thereafter in all patients if medically indicated.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 23 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Open Label, Single Arm, Clinical Study to Evaluate the Effect of Safinamide on Sleep Quality and Polysomnographic Parameters in Patients With Parkinson's Disease: the Safe Sleep Study
Actual Study Start Date : February 18, 2019
Estimated Primary Completion Date : April 30, 2021
Estimated Study Completion Date : April 30, 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: Safinamide
PO treatment: 2 weeks of treatment at dose 50 mg/day followed by 10 weeks at 100 mg/day
Drug: Safinamide
Safinamide taken per Os for 12 weeks
Other Name: Xadago

Outcome Measures
Primary Outcome Measures :
  1. Effect of safinamide on overall sleep quality [ Time Frame: 12 weeks ]
    To measure the change in PDSS-2 (Parkinson's Disease Sleep Scale Version 2) score and the changes in sleep maintenance (=total sleep time/partial sleep time) and sleep efficiency (=total sleep time/ time in bed) scores measured by polysomnography (PSG). PDSS-2 total score ranges from 0 (no disturbance) to 60 (maximum nocturnal disturbance). Scores > 18 are considered as relevant sleep disturbances.


Secondary Outcome Measures :
  1. Effect of safinamide on objective PSG sleep characterization [ Time Frame: 12 weeks ]
    To determine neurophysiological sleep parameters from PSG recording

  2. Effect of safinamide on subjective sleep quality and sleepiness [ Time Frame: 12 weeks ]
    To measure the change in subjective sleep quality as measured by PDSS-2 subscores and by the electronic diary "Sleep Fit app", and in daytime sleepiness as measured by ESS (Epworth sleepiness scale) score. PDSS-2 total score ranges from 0 (no disturbance) to 60 (maximum nocturnal disturbance). Scores > 18 are considered as relevant sleep disturbances. ESS score ranges from 0 to 24. Scores > 10 suggest relevant daytime sleepiness.

  3. Effect of safinamide on objective motor activity [ Time Frame: 12 weeks ]
    To determine the change in motor activity as measured by a specific objective measure of bradykinesia (FitTest) in the electronic diary "Sleep Fit app".

  4. Effect of safinamide on subjective motor activity [ Time Frame: 12 weeks ]
    To measure the change in motor activity as measured by UPDRS (Unified Parkinson's Disease Rating Scale). Higher UPDRS score indicates more severe impairment of non-motor and motor activities.

  5. Effect of safinamide on objective sleep parameters and motor symptoms [ Time Frame: 12 weeks ]
    To measure the change in sleep parameters and motor activity during the day and the night as measured by actigraphy.

  6. Effect of safinamide on non-motor symptoms [ Time Frame: 12 weeks ]
    To measure the change in depressive symptoms as measured by (BDI-II) Beck Depression Inventory and SAS (Starkstein Apathy Scale). Total BDI-II score ranges from 0 to 63 with higher total score indicating more severe depressive symptoms. Total SAS score ranges from 0 to 42 with higher scores indicating more severe apathy.

  7. Effect of safinamide on quality of life [ Time Frame: 12 weeks ]
    To measure the change in quality of life as measured by PDQ-39 (Parkinson's Disease Questionnaire-39). PDQ-39 is scored on a scale of 0 to 100, with lower scores indicating better health and high scores more severe symptoms.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years old
  • Fluctuating idiopathic PD patients according to UK Brain bank Criteria
  • Hoehn and Year II to IV under treatment
  • Sleep disturbance with a Pittsburgh Sleep Quality Index (PSQI) > 5
  • Treatment with L-DOPA, alone or with other dopaminergic drugs, at a stable dose since at least 28 days prior to inclusion
  • Treatment with all substances potentially acting on sleep and mood must be constant since at least 28 days prior to inclusion
  • Written informed consent
  • Willingness and ability to participate in the trial

Exclusion Criteria:

  • Off label use of safinamide
  • Early PD or absence of PD fluctuations
  • Concomitant treatment with other MAO-B inhibitors (wash-out period: at least 14 days)
  • Atypical Parkinsonism
  • Severe known sleep-related breathing disorders with any specific treatment or severe known sleep-related breathing disorders (apnoea-hypopnea index score >30/h) with or without a specific treatment
  • Dementia (MoCA < 26)
  • Severe depression (BDI-II ≥ 29)
  • Other severe psychiatric symptoms such as active psychosis or major hallucinations
  • Any previous or concomitant severe medical conditions or clinical laboratory abnormality which, in the clinical judgement of the Investigators, does not allow patients' participation into the study
  • Moderate or severe hepatic impairment, any type of retinopathy and/or any pathology that is deemed to be a contraindication according to safinamide's SmPC
  • Any concomitant treatment not allowed or contraindicated in the safinamide SmPC
  • Women who are pregnant or breast feeding
  • Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Alain Kaelin, Prof +41 (0)91 811 62 57 alain.kaelin@eoc.ch
Contact: Ilaria Bertaina, MD +41 (0)91 811 63 74 ilaria.bertaina@eoc.ch

Locations
Layout table for location information
Switzerland
Neurocenter of Southern Switzerland - Ente Ospedaliero Cantonale (EOC) Recruiting
Lugano, Switzerland, 6900
Contact: Alain Kaelin, Prof.    +41 (0)91 811 62 57    alain.kaelin@eoc.ch   
Contact: Ilaria Bertaina, MD    +41 (0)91 811 69 15 -    ilaria.bertaina@eoc.ch   
Sub-Investigator: Mauro Manconi, Prof.         
Sub-Investigator: Ilaria Bertaina, MD         
Sponsors and Collaborators
Alain Kaelin
Clinical Trial Unit Ente Ospedaliero Cantonale
Tracking Information
First Submitted Date  ICMJE April 19, 2019
First Posted Date  ICMJE May 30, 2019
Last Update Posted Date April 29, 2020
Actual Study Start Date  ICMJE February 18, 2019
Estimated Primary Completion Date April 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 29, 2019)
Effect of safinamide on overall sleep quality [ Time Frame: 12 weeks ]
To measure the change in PDSS-2 (Parkinson's Disease Sleep Scale Version 2) score and the changes in sleep maintenance (=total sleep time/partial sleep time) and sleep efficiency (=total sleep time/ time in bed) scores measured by polysomnography (PSG). PDSS-2 total score ranges from 0 (no disturbance) to 60 (maximum nocturnal disturbance). Scores > 18 are considered as relevant sleep disturbances.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2019)
  • Effect of safinamide on objective PSG sleep characterization [ Time Frame: 12 weeks ]
    To determine neurophysiological sleep parameters from PSG recording
  • Effect of safinamide on subjective sleep quality and sleepiness [ Time Frame: 12 weeks ]
    To measure the change in subjective sleep quality as measured by PDSS-2 subscores and by the electronic diary "Sleep Fit app", and in daytime sleepiness as measured by ESS (Epworth sleepiness scale) score. PDSS-2 total score ranges from 0 (no disturbance) to 60 (maximum nocturnal disturbance). Scores > 18 are considered as relevant sleep disturbances. ESS score ranges from 0 to 24. Scores > 10 suggest relevant daytime sleepiness.
  • Effect of safinamide on objective motor activity [ Time Frame: 12 weeks ]
    To determine the change in motor activity as measured by a specific objective measure of bradykinesia (FitTest) in the electronic diary "Sleep Fit app".
  • Effect of safinamide on subjective motor activity [ Time Frame: 12 weeks ]
    To measure the change in motor activity as measured by UPDRS (Unified Parkinson's Disease Rating Scale). Higher UPDRS score indicates more severe impairment of non-motor and motor activities.
  • Effect of safinamide on objective sleep parameters and motor symptoms [ Time Frame: 12 weeks ]
    To measure the change in sleep parameters and motor activity during the day and the night as measured by actigraphy.
  • Effect of safinamide on non-motor symptoms [ Time Frame: 12 weeks ]
    To measure the change in depressive symptoms as measured by (BDI-II) Beck Depression Inventory and SAS (Starkstein Apathy Scale). Total BDI-II score ranges from 0 to 63 with higher total score indicating more severe depressive symptoms. Total SAS score ranges from 0 to 42 with higher scores indicating more severe apathy.
  • Effect of safinamide on quality of life [ Time Frame: 12 weeks ]
    To measure the change in quality of life as measured by PDQ-39 (Parkinson's Disease Questionnaire-39). PDQ-39 is scored on a scale of 0 to 100, with lower scores indicating better health and high scores more severe symptoms.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Safinamide on Sleep Quality in Patients With Parkinson's Disease
Official Title  ICMJE A Prospective, Open Label, Single Arm, Clinical Study to Evaluate the Effect of Safinamide on Sleep Quality and Polysomnographic Parameters in Patients With Parkinson's Disease: the Safe Sleep Study
Brief Summary Patients suffering of Parkinson's Disease will be treated with 50 mg/day of Safinamide per os for 2 weeks (escalation phase). Then, safinamide will be increased up to 100 mg/day and, if tolerated, the treatment will be taken for 10 more weeks (maintenance phase). Total treatment 12 weeks.
Detailed Description

Adult patients affected by PD and suffering from motor fluctuations will be screened for participation.

If the inclusion and exclusion criteria are met, the participant will enter in the baseline assessment phase and undergo 1 night baseline PSG and 1 week baseline actigraphy. The patient will then start the treatment with 50 mg/day of Safinamide per os for 2 weeks (escalation phase). Then, safinamide will be increased up to 100 mg/day and, if tolerated, the treatment will last for 10 weeks (maintenance phase). At week 12 (end of treatment), the questionnaires, actigraphy and PSG will be repeated. A safety follow-up visit is scheduled 4 weeks after study treatment completion.

The treatment will be continued thereafter in all patients if medically indicated.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Idiopathic Parkinson's Disease (at Later Stage)
Intervention  ICMJE Drug: Safinamide
Safinamide taken per Os for 12 weeks
Other Name: Xadago
Study Arms  ICMJE Experimental: Safinamide
PO treatment: 2 weeks of treatment at dose 50 mg/day followed by 10 weeks at 100 mg/day
Intervention: Drug: Safinamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 29, 2019)
23
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 30, 2021
Estimated Primary Completion Date April 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥ 18 years old
  • Fluctuating idiopathic PD patients according to UK Brain bank Criteria
  • Hoehn and Year II to IV under treatment
  • Sleep disturbance with a Pittsburgh Sleep Quality Index (PSQI) > 5
  • Treatment with L-DOPA, alone or with other dopaminergic drugs, at a stable dose since at least 28 days prior to inclusion
  • Treatment with all substances potentially acting on sleep and mood must be constant since at least 28 days prior to inclusion
  • Written informed consent
  • Willingness and ability to participate in the trial

Exclusion Criteria:

  • Off label use of safinamide
  • Early PD or absence of PD fluctuations
  • Concomitant treatment with other MAO-B inhibitors (wash-out period: at least 14 days)
  • Atypical Parkinsonism
  • Severe known sleep-related breathing disorders with any specific treatment or severe known sleep-related breathing disorders (apnoea-hypopnea index score >30/h) with or without a specific treatment
  • Dementia (MoCA < 26)
  • Severe depression (BDI-II ≥ 29)
  • Other severe psychiatric symptoms such as active psychosis or major hallucinations
  • Any previous or concomitant severe medical conditions or clinical laboratory abnormality which, in the clinical judgement of the Investigators, does not allow patients' participation into the study
  • Moderate or severe hepatic impairment, any type of retinopathy and/or any pathology that is deemed to be a contraindication according to safinamide's SmPC
  • Any concomitant treatment not allowed or contraindicated in the safinamide SmPC
  • Women who are pregnant or breast feeding
  • Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alain Kaelin, Prof +41 (0)91 811 62 57 alain.kaelin@eoc.ch
Contact: Ilaria Bertaina, MD +41 (0)91 811 63 74 ilaria.bertaina@eoc.ch
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03968744
Other Study ID Numbers  ICMJE NSI-SAF-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Alain Kaelin, Ente Ospedaliero Cantonale, Bellinzona
Study Sponsor  ICMJE Alain Kaelin
Collaborators  ICMJE Clinical Trial Unit Ente Ospedaliero Cantonale
Investigators  ICMJE Not Provided
PRS Account Ente Ospedaliero Cantonale, Bellinzona
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP