Clinical trial NCT04618978: Periodic Leg Movements' Diagnosis in Spinal Cord Injury: Actigraphy as an Alternative for Polysomnography?
Official title: Periodic Leg Movement's Diagnosis in Spinal Cord Injury: Actigraphy as an Alternative for Polysomnography?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Spinal Cord Injuries
Periodic Limb Movement Disorder
Keywords: spinal cord injury
multiple sclerosis
periodic leg movements
spasticity
periodic limb movement disorder
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-11-06
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Periodic Limb Movements during Sleep (PLMs) are episodes of repetitive, stereotypical, hallux or foot movements. They could induce sleep disturbance, fatigue, daytime sleepiness and impaired quality of life but also increased cardiovascular risk by rising heart rate and blood pressure at night. Gold standard for PLMs diagnosis is based on electromyographic recording of tibialis anterior muscle during full night polysomnography (PSG).

PLMs prevalence is higher in patients with spinal cord injury (SCI) possibly due to a loss of encephalic inhibition on a spinal motion generator. In these patients, PLMs can also be wrongly considered as spasms sometimes leading to the unjustified implantation of an intrathecal Lioresal pump.

In the general population, drug treatments for PLMs, particularly dopamine agonists, limit the impact of these abnormal movements on sleep fragmentation, daytime alertness and quality of life. Underdiagnosed PLMs in SCI patients can lead to exacerbate cognitive, mood and painful disorders due to the close interaction between sleep disorders and neurocognitive, psychological and painful manifestations.

PLMs appropriate diagnosis appeared mandatory in those patients but accessibility and delayed availability remain challenging. In addition, sleep laboratories are often unable to accommodate with SCI patients.

In this context, actigraphy, an easy-to-use, cheaper and easily renewable diagnostic tool would be interesting. In the general population, sensitivity to diagnose PLMs was between 0.79 and 1 and specificity between 0.6 and 0.83. Due to lower limbs impairment, increased specificity is expected SCI patients (decrease voluntary activity).

The new generation of actigraph (MotionWatchR) could have better characteristics thanks to the development of a specific software which integrate both lower limbs in the same analysis.

As primary objective, this prospective monocentric study aims to evaluate the performances of lower limbs actigraphy for PLMs diagnosis versus gold standard.

Detailed description: As secondary objectives, the study aims to:

* Estimate positive and negative predictive values;
* Identify the diagnostic threshold of PLMs index with actigraphy;
* Study concordance between actigraphy and polysomnography to detect lower limbs movements;
* Evaluate reproducibility between 2 readers and with the new PLMs software;
* Study actigraphy reproducibility for this indication over 3 consecutive nights in the same patients (ancillary study);
* Compare diagnostic performance according to SCI completeness (AIS-A vs AIS-B, C, D) and underlying pathology (MS, SCI);
* Compare installation and interpretation times between actigraphy and PSG.

PLMs appropriate diagnosis appeared mandatory in SCI patients however the accessibility and the delay of availability remain challenging for severe SCI complications in care management.

The study team hypothesize that actigraphy could be able to diagnose PLMs with sufficient reliability (AUC (area under the curve) around 80%) compared to the gold standard (polysomnography) in patients with spinal cord injuries.

Intervention: During a scheduled night recording (polysomnography) 3 actigraphs will be added (1 on the wrist, and 1 on each foot).

Equipment: MotionWatch8®, CamNtech® (marking CE Class 1 device; accord FDA (K132764)).

Methods:

All consecutive eligible patients followed in our tertiary care center (for whom a full night polysomnography is already scheduled) will be informed of the study and proposed to participate.

After signing the informed consent form, all subjects will undergo a full-night examinations: polysomnography (already scheduled in usual care) and actigraphy (addition of 3 devices):

* 1 classic actigraph on the wrist to detect light and identify inactivity periods compatible with sleep.
* 2 new generation Actiwatch actigraphs (MotionWatch) placed on the feet. Polysomnography will incorporate tibialis anterior EMG recording and will be scored by one sleep specialist following American Academy of Sleep Medicine (AASM) scoring criteria.

Actigraphy analysis will be provided by:

* An automated software specially developed for this indication (PLMsanalysis software, camNtechR).
* A nurse reading unaware of both software's and PSG results.
* A second reading will be provided by a second nurse, also unaware of the result of the polysomnography.

Actigraphy results will not be communicated to patients or physicians and therefore will not affect patient management.

At the end of the evaluation period, each patient will be offered, if needed, treatment and follow-up in the sleep unit as in usual care.

A study of actigraphy reproducibility will be carried out in a sample of 33 subjects. This study will take place over three consecutive nights during an already scheduled hospitalization (no additional hospitalization night for patients).

Statistical analysis: as described in Outcome Measures.

Eligibility criteria: Inclusion Criteria:

* Patient With Spinal Cord Injury from traumatic or medical aetiology (including patient with multiple sclerosis);
* Motor testing stability for at least 6 months prior to inclusion;
* Patients with complete or incomplete SCI (AIS-A, B, C, D and E);
* Neurological level between C4 and L1;
* Aged \>18 years;
* Patients with already scheduled full night polysomnography (PSG);
* Affiliated to social security system;
* Absence of medical intercurrent event.

Exclusion Criteria:

Specific criteria:

* History of lower limbs amputation ;
* Cutaneous lesion compromising actigraphy positioning
* Presence of spinal cord stimulation equipment, Brindley electrodes, history of spinal cord surgery.

No-specific criteria:

* Patient refusal;
* Participation in another interventional study involving human participants
* Unable to sign informed consent form;
* Emergency condition;
* Legal protection (i.e. incompetence to provide consent, guardianship, curator or incarceration);
* No affiliation to a social security system.

Primary outcomes:
measure: The Receiver Operating Characteristic (ROC) analysis
timeFrame: Through study completion, an average of 3 years
Secondary outcomes:
measure: Predictive values estimation
timeFrame: Through study completion, an average of 3 years
measure: Threshold of PLMs Index
timeFrame: up to 24 hours
measure: Lower limb nocturnal movements evaluation
timeFrame: up to 24 hours
measure: PLMs diagnosis based on the actigraphy
timeFrame: Through study completion, an average of 3 years
measure: Kappa coefficient
timeFrame: Through study completion, an average of 3 years
measure: Actigraphy diagnostic performance
timeFrame: Through study completion, an average of 3 years
measure: Installation time
timeFrame: Through study completion, an average of 3 years
measure: Interpretation time
timeFrame: Through study completion, an average of 3 years
Other outcomes:
Locations:
city: Garches
country: France
facility: Physiologie, explorations fonctionnelles - Unité des pathologies du sommeil, Hôpital Raymond Poincaré, APHP
Study officials:
affiliation: Physiologie, explorations fonctionnelles - Unité des pathologies du sommeil, Hôpital Raymond Poincaré, APHP
name: Marie Christine BLANDIN
role: PRINCIPAL_INVESTIGATOR
affiliation: Physiologie, explorations fonctionnelles - Unité des pathologies du sommeil, Hôpital Raymond Poincaré, APHP
name: Antoine LEOTARD, MD
role: STUDY_DIRECTOR
References:
citation: Siddiqui F, Strus J, Ming X, Lee IA, Chokroverty S, Walters AS. Rise of blood pressure with periodic limb movements in sleep and wakefulness. Clin Neurophysiol. 2007 Sep;118(9):1923-30. doi: 10.1016/j.clinph.2007.05.006. Epub 2007 Jun 27.
citation: Proserpio P, Lanza A, Sambusida K, Fratticci L, Frigerio P, Sommariva M, Stagni EG, Redaelli T, De Carli F, Nobili L. Sleep apnea and periodic leg movements in the first year after spinal cord injury. Sleep Med. 2015 Jan;16(1):59-66. doi: 10.1016/j.sleep.2014.07.019. Epub 2014 Oct 7.
citation: Foschi M, Rizzo G, Liguori R, Avoni P, Mancinelli L, Lugaresi A, Ferini-Strambi L. Sleep-related disorders and their relationship with MRI findings in multiple sclerosis. Sleep Med. 2019 Apr;56:90-97. doi: 10.1016/j.sleep.2019.01.010. Epub 2019 Jan 21.
citation: Telles SC, Alves RS, Chadi G. Spinal cord injury as a trigger to develop periodic leg movements during sleep: an evolutionary perspective. Arq Neuropsiquiatr. 2012 Nov;70(11):880-4. doi: 10.1590/s0004-282x2012001100011.
citation: Levy J, Hartley S, Mauruc-Soubirac E, Leotard A, Lofaso F, Quera-Salva MA, Bensmail D. Spasticity or periodic limb movements? Eur J Phys Rehabil Med. 2018 Oct;54(5):698-704. doi: 10.23736/S1973-9087.17.04886-9. Epub 2017 Dec 4.
citation: Allen R. Dopamine and iron in the pathophysiology of restless legs syndrome (RLS). Sleep Med. 2004 Jul;5(4):385-91. doi: 10.1016/j.sleep.2004.01.012.
citation: Guilleminault C, Flagg W. Effect of baclofen on sleep-related periodic leg movements. Ann Neurol. 1984 Mar;15(3):234-9. doi: 10.1002/ana.410150304.
citation: Plante DT. Leg actigraphy to quantify periodic limb movements of sleep: a systematic review and meta-analysis. Sleep Med Rev. 2014 Oct;18(5):425-34. doi: 10.1016/j.smrv.2014.02.004. Epub 2014 Feb 17.
citation: Kobayashi M, Namba K, Ito E, Nishida S, Nakamura M, Ueki Y, Furudate N, Kagimura T, Usui A, Inoue Y. The validity of the PAM-RL device for evaluating periodic limb movements in sleep and an investigation on night-to-night variability of periodic limb movements during sleep in patients with restless legs syndrome or periodic limb movement disorder using this system. Sleep Med. 2014 Jan;15(1):138-43. doi: 10.1016/j.sleep.2013.08.790. Epub 2013 Oct 31.
citation: Ferri R, Fulda S, Manconi M, Hogl B, Ehrmann L, Ferini-Strambi L, Zucconi M. Night-to-night variability of periodic leg movements during sleep in restless legs syndrome and periodic limb movement disorder: comparison between the periodicity index and the PLMS index. Sleep Med. 2013 Mar;14(3):293-6. doi: 10.1016/j.sleep.2012.08.014. Epub 2012 Oct 12.