Circadian & Homeostatic Synchronization Effect on Waking Mobility in Parkinson's Disease

NCT04467632 | Withdrawn

• 1 other identifier: 19_RIPH2-12
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Sleep benefit (SB) consists of a spontaneous, transient and inconsistent improvement of the mobility occurring on morning awakening in approximately 40% of Parkinson's disease (PD) patients, before taking the first morning dose of dopaminergic drugs. The SB could represent a pathway for the development of new therapeutic strategies for motor symptoms in PD. Being a seemingly unpredictable phenomenon and a great variability daily, inter- and intra-subject, the SB study requires multiple and repeated assessments of mobility for several days. An experimental home setting would be optimal for this purpose in terms of cost-effectiveness and patient acceptability. In addition, since the extent and nature of SB have not been well characterized so far, and the magnitude of its variability is unknown, a reliable assessment method, independent of observers and situation, the SB is a requirement of further research in this area. A recently developed technique combining machine learning algorithms with wireless portable sensors (accelerometers and gyroscopes) and software applications could be particularly promising for characterizing the complexity and multiplicity of SBs in. With this technique, repeated and multiple assessments of mobility can be performed in the homes of patients without the constant presence of a researcher. This approach offers several advantages in terms of cost-effectiveness, feasibility and acceptability of study protocols by patients. It also improves the ecological validity of subjective and objective estimates of mobility in these patients. The investigators chose to conduct this preliminary study on patients with PD rather than on healthy subjects, because SB is a phenomenon that has been described so far only in this population. Investigators also consider that the feasibility of the study will depend mainly on the patients' ability to move and the context of their own illness. SB is a phenomenon induced by sleep. The propensity and timing of sleep depend on the coordinated interaction of the duration of the previous awakening (homeostatic process) and a circadian signal (circadian process). In order to better understand SB, it is necessary to study the reciprocal influences of the circadian and homeostatic process. Investigators have devised a new paradigm to "shift" the circadian process phase around the homeostatic process, maintained under constant conditions, in order to observe the effect of the synchronism or desynchronization of these two processes on the awakening mobility of patients with an MP. This experimental approach was approved by Professor Aleksandar Videnovic (Harvard University School of Medicine, USA), opinion leader on circadian rhythmicity in the MP and scientific collaborator of this study. As a first step, the investigators plan to implement a technology-assisted home-based methodology, to validate it in PD patients and to verify the logistic feasibility of this method-assisted approach in a small group of patients, in order to to be able to apply this paradigm in larger scientific projects.

Conditions

Parkinson's Disease

Keywords

Parkinson's Disease; Sleep benefit; circadian process; homeostatic process; circadian and homeostatic synchronization

Outcome Measures

Primary Outcomes (8)

• Validation of the objective metrics of mobility

  The validity of the mobility assessment by Inertial Measurement Unit (IMU) wearable sensors will be verified. It will be defined as the accuracy of the machine learning algorithm to predict patients' motor status compared to the motor status assessed at clinical examination by means of the MDSUPDRS- III scale and the Fit test. Prediction by machine learning will be compared with the MDS-UPDRS-III total score and with the 3.14 item (global clinical impression of mobility) of the same scale. The patients will be asked to perform all the motor tasks of the MDS-UPDRS-III scale and the finger tapping test (Fit test) with both hands wearing the IMU system.

  12 months

• Objective and subjective mobility

  Prediction of mobility by machine learning based on data from IMU wearable sensors; finger tapping test; VAS motor

  12 months

• Sleep and sleepiness

  Measured by sleep diary, SSS

  12 months

• Cognition (electronic Stroop test)

  12 months

• Emotional state

  Measured by Visual Analog Scale(VAS) mood/anxiety

  12 months

• Fatigue

  Measured by VAS fatigue

  12 months

• Circadian phase

  Continuously for skin body temperature and repeated samples (every 30' for a total of 9 samples, in the evening around the bed time, for salivary DLMO

  12 months

• Sleep homeostasis (SWA)

  Calculated based on the EEG recording acquired by means of nocturnal portable polysomnography.

  12 months

Secondary Outcomes (8)

• Chronotype

  12 months

• Sleep habits, sleep and wake-related symptoms, sleep quality

  12 months

• PD-specific sleep and wake-associated symptoms

  12 months

• Daytime symptoms of bad or insufficient sleep

  12 months

• Modification of mobility on morning awakening

  12 months

Study Arms (1)

Patients affected with idiopathic Parkinson Disease

EXPERIMENTAL

Other: Validation of the mobility assessment by IMU wearable sensors; Other: Testing in real-life conditions at patients' home in a small group of subjects

Interventions

Validation of the mobility assessment by IMU wearable sensors OTHER

The validity of the mobility assessment by IMU wearable sensors will be verified in Work Package 3. It will be defined as the accuracy of the machine learning algorithm to predict patients' motor status compared to the motor status assessed at clinical examination by means of the MDS-UPDRS-III scale and the Fit test. Prediction by machine learning will be compared with the MDS-UPDRS-III total score and with the 3.14 item (global clinical impression of mobility) of the same scale. The patients will be asked to perform all the motor tasks of the MDS-UPDRS-III scale and the finger tapping test (Fit test) with both hands wearing the IMU system. A subset of minimal motor tasks allowing good prediction of the patient's motor status by the machine learning algorithm will then be selected for Work Package 4.

Patients affected with idiopathic Parkinson Disease

Testing in real-life conditions at patients' home in a small group of subjects OTHER

Baseline Phase B1: Observation phase: 1-week wrist actigraphy and sleep diary to assess habitual activity/rest routines. B2: Nocturnal sleep consolidation phase: 2 weeks: timed light exposure, constant sleep/wake routine and sleep restriction of 1 hour/night (based on habitual activity).

Patients affected with idiopathic Parkinson Disease

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients \> 18 years old;
• Patients affected with idiopathic PD, of both sexes;
• Hoehn and Yahr stage of 2 to 4 in the "on" state;
• Stable antiparkinsonian and/or psychotropic medications for at least 4 weeks prior to study screening;
• Reliable partner/caregiver to assist the patient during the study procedures;
• Affiliated person or beneficiary of a social security scheme;

You may not qualify if:

• Patients \< 18 years old;
• Atypical parkinsonian syndromes;
• Dementia;
• Treatment with extended-release dopaminergic drugs (excluding extended release levodopa given no later than 6 hours before the habitual bedtime);
• Use of hypno-sedative drugs or stimulants;
• Use of antidepressants unless on a stable dose for at least 3 months;
• Travel through 2 time zones within 90 days prior to study screening;
• Visual abnormalities that may interfere with light therapy, such as significant cataracts, narrow angle glaucoma or blindness;
• Any other medical condition potentially interfering with the assessment of mobility (e.g. limb amputation, post-stroke paralysis, severe osteo-articular condition);
• Any condition limiting the capability of the subject to understand the task to be performed at home by the patient himself (e.g. aphasia, oligophrenia);
• Severely altered physical and/or psychological health which, according to, the investigator, could affect the participant's compliance of the study;
• Inadequate housing conditions to perform home assessments;
• Patients refusing to participate in the study;
• Patients under legal guardianship or curatorship, pregnant and breastfeeding women, women of child-bearing age, persons in emergency situations;

Sponsors & Collaborators

• University Hospital Center of Martinique: lead

Study Sites (1)

CHU de Martinique

Fort-de-France, 97200, France

Location

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Pietro Luca RATTI, MD

  CHU de Martinique

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2019
• First Posted: July 13, 2020
• Study Start: October 1, 2019
• Primary Completion: October 1, 2021
• Study Completion: April 1, 2022
• Last Updated: July 13, 2020

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)