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Role of Sleep on Motor Learning in Parkinson's Disease and Healthy Older Adults (TARGET-SLEEP)

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ClinicalTrials.gov Identifier: NCT04144283
Recruitment Status : Recruiting
First Posted : October 30, 2019
Last Update Posted : July 17, 2020
Sponsor:
Information provided by (Responsible Party):
Alice Nieuwboer, KU Leuven

Brief Summary:
People with Parkinson's disease (pwPD) often present difficulty consolidating newly learned skills into long-term memory. Sleep facilitates motor memory consolidation in healthy adults, especially in combination with targeted memory reactivation (TMR). TMR works by adding associated sounds during learning that are replayed during sleep and thus reinforce the recently formed neural connections. Importantly, recent work suggested that consolidation during sleep may be preserved in pwPD, but robust findings are lacking and have not involved TMR. The objective of the present study is to address this imperative question by investigating the effect of napping on motor memory consolidation by experimentally manipulating exposure to sleep and TMR for the first time. Concretely, the investigators will first compare the effect of a 2-hour nap to that of a wake control period in pwPD and healthy age-matched controls. A validated motor sequence learning task will be used to test for behavioral markers of motor learning and polysomnography with electroencephalography (EEG) will be conducted to study the neural correlates of sleep-related motor learning effects. In a second experiment, the investigators will then test the effects of adding TMR during post-learning sleep, by comparing performance on two motor sequences of which only one is reactivated during post-learning napping using auditory TMR.

Condition or disease Intervention/treatment Phase
Parkinson Disease Aging Behavioral: NAP Behavioral: WAKE Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Performance on the MSL task (Experiment 1, n=80) will be compared between a group that undergoes a 2-hour post-learning NAP and a group that will undergo a 2-hour post-learning WAKE period. Participants will be randomized (1:1) to either the NAP or WAKE group. Performance on the SRT task (Experiment 2, n=40) will be compared between the sequence that was replayed during the post-learning nap using auditory TMR (replay) and the sequence that was not replayed (no-replay). The order of sequence blocks during learning and retest as well as the sequence selected for TMR will be randomized across participants. Randomization for both experiments will be done by an independent researcher who is not involved in the measurements of any of the studies using a computerized random number generation technique.
Masking: Single (Participant)
Masking Description: For experiment 2, participants will be told that sounds may be played during the nap or wake period, without further knowledge on the anticipated effects of these sounds.
Primary Purpose: Basic Science
Official Title: Towards Retention of Motor Learning in Parkinson's Disease: Understanding Sleep-related Effects of Consolidation
Actual Study Start Date : November 15, 2019
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: NAP
The NAP group will undergo a post-learning 2-hour sleep opportunity in Experiment 1.
Behavioral: NAP

For experiment 1, the NAP group will undergo a post-learning 2-hour diurnal sleep opportunity (i.e. 'nap') without cues.

For experiment 2 the NAP+TMR group will undergo a post-learning 2-hour diurnal sleep opportunity (i.e. 'nap') with auditory TMR. The learning related sounds will be presented to participants at 140% of their minimal auditory detection threshold during stage 2 and stage 3 of NREM sleep.


Active Comparator: WAKE
The WAKE group will undergo a post-learning 2-hour period of quiescent wakefulness in Experiment 1.
Behavioral: WAKE
For experiment 1, the WAKE group will undergo a post-learning 2-hour period of quiescent wakefulness without cues.




Primary Outcome Measures :
  1. Experiment 1 - MSL single task: Offline consolidation [ Time Frame: Change in PI between the first 4 blocks immediately after the 2-hour NAP or WAKE intervention (Retest 1) and the last 4 blocks of learning immediately prior to the intervention. ]
    Participants perform a self-initiated MSL task by tapping a five-element finger sequence presented on screen as rapidly and accurately as possible with their non-dominant hand for 18 blocks during learning and again at each retest assessment. Each block consists of 50 key presses (ideally 10 sequences) and is followed by a rest block of 15-20 seconds without finger tapping. A two-minute rest period will be implemented after 14 blocks to further minimize the effects of fatigue on the last 4 blocks that are used to calculate the primary outcome. Performance on the MSL will be assessed using the 'Performance Index (PI)' [PI=exp^-(seqDur) * exp^-(Errors/12) * 100], taking both speed and accuracy into account (King et al. 2017b). After learning the MSL, participants are randomly allocated to undergo a post-learning 2-hour diurnal sleep opportunity (NAP) or 2-hour period of quiescent wakefulness (WAKE) before being reassessed on the MSL.

  2. Experiment 1 - MSL single task: Retention [ Time Frame: Change in PI between the first 4 blocks after the 24-hour retention period (Retest 2) and the last 4 blocks of Retest 1 immediately after the 2-hour NAP or WAKE intervention. ]
    The same MSL task as described above in Primary outcome 1 is again repeated 24-hours after Retest 1 in order to assess whether the sleep-related effects on motor memory consolidation are retained in the long-term (Retest 2).

  3. Experiment 2, SRT single task: Offline consolidation [ Time Frame: Change in PI between the first 4 blocks immediately after the nap+TMR intervention (Retest 1) and the last 4 blocks of learning immediately prior to the intervention. ]
    Experiment 2 is similar to experiment 1, except that participants will learn two motor sequences that are visually and auditory cued by means of a serial reaction time task (SRT). After learning both sequences, participants will nap for 2-hours, but this time while one of the two auditory sequences will be replayed during NREM sleep. Performance on both sequences will be re-assessed immediately after the intervention (Retest 1), and again at 24h retention (Retest 2). The PI will be used to assess performance on the task and compared between the sequence that was replayed and the sequence that is not replayed.

  4. Experiment 2, SRT single task: Retention [ Time Frame: Change in PI between the first 4 blocks after the 24-hour retention period (Retest 2) and the last 4 blocks of Retest 1 immediately after the 2-hour NAP+TMR or WAKE+TMR intervention. ]
    The same SRT task as described above in Primary outcome 3 is again repeated 24-hours after Retest 1 in order to assess whether the sleep- and TMR-related effects on motor memory consolidation are retained in the long-term.


Secondary Outcome Measures :
  1. Experiment 1 - MSL dual tasking: Offline consolidation [ Time Frame: Change in PI between the 4 blocks of dual tasking immediately after the 2-hour NAP or WAKE intervention (Retest 1) and the 4 blocks of dual tasking during learning prior to the intervention. ]
    The same MSL task as described above in Primary outcome 1 will be performed for an additional 4 blocks at learning and 4 blocks immediately after the intervention (Retest 1), but this time while participants consecutively perform a shape-counting dual task. During the single-task MSL condition, participants view a fixation cross in the middle of the screen, with the sequence presented above the fixation cross. During the MSL dual-task condition, the fixation cross pseudo-randomly changes shape (e.g. "X" or "O") and participants are instructed to count how often in each block a shape change occurred, while they continue to perform the MSL. Participant's responses on the dual task condition will be recorded after each block.

  2. Experiment 1 - MSL dual tasking: Retention [ Time Frame: Change in PI between the 4 blocks of dual tasking after the 24-hour retention period (Retest 2) and the 4 blocks of dual tasking at Retest 1 immediately after the 2-hour NAP or WAKE intervention. ]
    The same MSL with dual task as described above in Secondary outcome measure 1 will again be repeated 24-hours after Retest 1.

  3. Experiment 2 - SRT dual tasking: Offline consolidation [ Time Frame: Change in PI between the 4 blocks of dual tasking immediately after the 2-hour NAP+TMR or WAKE+TMR intervention (Retest 1) and the 4 blocks of dual tasking during learning prior to the intervention. ]
    The same SRT task as described above in Primary outcome 3 will be performed for an additional 4 blocks at learning and 4 blocks immediately after the intervention (Retest 1), but this time while participants consecutively perform a shape-counting dual task. During the single-task SRT condition, participants view empty squares in the middle of the screen, which are filled (i.e. highlighted) one by one in the order of the sequence that is being learned. During the SRT dual task condition, the same squares pseudo-randomly fill with a different shape (e.g. "X" or "O") and participants are instructed to count how often in each block a shape change occurred, while they continue to perform the SRT. Participant's responses on the dual task condition will be recorded after each block.

  4. Experiment 2 - SRT dual tasking: Retention [ Time Frame: Change in PI between the 4 blocks of dual tasking after the 24-hour retention period (Retest 2) and the 4 blocks of dual tasking at Retest 1 immediately after the 2-hour NAP+TMR or WAKE+TMR intervention. ]

    The same SRT with dual task as described above in Secondary outcome measure 7 will again be repeated 24-hours after Retest 1.

    All comparisons using the PI as the main dependent variable of interest, as well as the tertiary outcomes are listed in the attached statistical analysis plan.




Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Right handed
  • Can read and understand Dutch
  • Age equal or greater than 40 years
  • PwPD will have a clinical diagnosis of idiopathic Parkinson's disease made by a Neurologist
  • Completed written informed consent approved by the assigned medical ethical committee

Exclusion Criteria:

  • Receiving deep brain stimulation
  • Enrollment in an interventional trial for Parkinson's disease therapy
  • Severe sleep apnea determined as an Apnea/Hypopnea index (AHI) > 30 during the screening polysomnography (PSG)
  • Cognitive impairment that could question the participant's ability to provide voluntary informed consent as determined by an Mini Mental State Examination score <24
  • Co-morbidities that would hamper interpretation of MSL or SRT learning, such as musculoskeletal abnormalities, as determined by a Neurologist or Physical Therapist.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04144283


Contacts
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Contact: Moran Gilat, PhD +3216329427 moran.gilat@kuleuven.be

Locations
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Belgium
UZ Leuven Recruiting
Leuven, Vlaams-Brabant, Belgium, 3000
Contact: Moran Gilat, PhD    +32 16 32 94 27    moran.gilat@kuleuven.be   
Principal Investigator: Alice Nieuwboer, PhD         
Sub-Investigator: Moran Gilat, PhD         
Sub-Investigator: Genevieve Albouy, PhD         
Sub-Investigator: Dries Testelmans, MD, PhD         
Sub-Investigator: Bertien Buyse, MD, PhD         
Sub-Investigator: Brad King, PhD         
Sub-Investigator: Pieter Ginis, PhD         
Sub-Investigator: Evelien Nackaerts, PhD         
Sponsors and Collaborators
KU Leuven
Investigators
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Principal Investigator: Alice Nieuwboer, PhD University of Leuven
  Study Documents (Full-Text)

Documents provided by Alice Nieuwboer, KU Leuven:
Statistical Analysis Plan  [PDF] July 14, 2020

Publications:
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Responsible Party: Alice Nieuwboer, Professor, KU Leuven
ClinicalTrials.gov Identifier: NCT04144283    
Other Study ID Numbers: S61792
838576 ( Other Grant/Funding Number: European Commission Horizon 2020, MSCA )
2019-J4121350-212854 ( Other Grant/Funding Number: King Baudouin Foundation Belgium )
First Posted: October 30, 2019    Key Record Dates
Last Update Posted: July 17, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pseudonymized data files may be shared upon publication of the results, but on no occasion will any identifiable information or contact details of the participants be presented or made visible. Information on data management is provided to participants on the written informed consent form. The polysomnography data will be made available for open access sharing if approval is obtained from the participant on the participant consent form. The informed consent form will include modules explaining why open access sharing is requested. The subjects will be informed about the data that is intended for open access sharing and will have the opportunity to opt out without any consequences to their current or future participation or care at the University of Leuven (KU Leuven) or University hospitals Leuven (UZ Leuven), via a tick-box on the informed consent form. The subject's privacy will be protected.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Upon publication of the study findings for a period of five years.
Access Criteria: Pseudonymised data will only be shared with research projects that have obtained written approval from a Medical Ethical Committee to use the data for a specific research purpose. Requests for accessing the data should then be made to the PI of the study, Prof Nieuwboer.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alice Nieuwboer, KU Leuven:
Parkinson's disease
Ageing
Rehabilitation
Sleep
Motor learning
Targeted Memory Reactivation
Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases