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

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

Interventions

OTHER

Validation of the mobility assessment by IMU wearable sensors

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.

OTHER

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

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).

OTHER

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

Intervention phase * Phase A (11 days): subjects will receive one hour of morning and afternoon light exposure twice a day: * Day #1: baseline assessment of outcome measures; * Days #2 to #6: bright light in the morning (active treatment) + dim light in the afternoon (placebo), to progressively advance circadian phase of 30' per day (phase advance of 2.5 hours obtained at day 6); * Days #7 to #11: dim light in the morning + bright light in the afternoon to revert the circadian phase to the baseline of 30' per day. * Washout: 6 days. No intervention during this phase, to stabilise the reverted circadian rhythm to baseline, for phase B to be held at the same conditions as phase A. * Phase B (11 days): similar as in phase A: * Day #1: similar as in phase A; * Days #2 to #6: reverted conditions compared to phase A. * Days #7 to #11: reverted conditions compared to phase A.

Sponsors & Collaborators

• University Hospital Center of Martinique

  lead OTHER

Principal Investigators

• Pietro Luca RATTI, MD · CHU de Martinique

Study Design

Allocation

NA

Purpose

OTHER

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-10-31

Primary Completion

2021-10-31

Completion

2022-04-30

Countries

• France