Motor Control During Rapid Eye Movement (REM) Sleep Behaviour Disorder

Parkinson Disease Clinical Trial

— RevesParkNST  

Official title:

Subthalamic Nuclei (STN) Local Field Potentials to Investigate Motor Control During REM Sleep Behaviour Disorder (TCSP) Secondary to Idiopathic Parkinsons Disease (PD)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01886131
• Other study ID #: 12 388 02
• Secondary ID: AOL2012
• Status: Terminated
• Phase: N/A
• First received: June 20, 2013
• Last updated: February 21, 2017
• Start date: June 2013
• Est. completion date: July 2014

Study information

• Verified date: February 2017
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To compare the electrical activity of SubThalamic Nuclei (STN), by mean of local field potentials recordings, during the phasic behaviours of RBD with the electrical activity recorded at this level during the execution of voluntary movements during the "off" and the "on" phases in patients with RBD secondary to PD.

Description:

Patient with severe Parkinson's disease (PD) with motor fluctuations are akinetic and bradykinetic during the "off" phases. Their motor status dramatically improves during "on" phases, due to the effect of dopaminergic agents.

In the off phases, the plasmatic levels of dopaminergic drugs are the lowest. The plasmatic levels of dopaminergic drugs are also very low during nocturnal sleep.

Nevertheless, PD patients may show vigorous and rapid movements during REM Behaviour Disorder (RBD). Thirty-three to 46% of the patients with PD have RBD.

Akinesia and bradykinesia are the consequence of a hyperactivity of the SubThalamic Nuclei (STN). The electrophysiological correlate of this hyperactivity causing akinesia and bradykinesia is represented by STN beta activity, recorded by local field potentials.

STN beta activity is not present during the execution of a voluntary movement at an "on" phase. Levodopa therapy, which can revert akinesia and bradykinesia, also suppress STN beta activity in PD patients The STN is the surgical target for Deep Brain Stimulation (DBS) of the basal ganglia to improve the motor symptoms of PD.

The STN has bilateral connections with the laterodorsal nucleus/pedunculopontine tegmentum (LDT/PPN), a key structure for REM sleep regulation.

The investigators hypothesize that during the execution of the phasic motor behaviours of RBD the pattern of discharge of STN differs from the one observed during voluntary movements in the "off" phase, in PD patients. In other terms, we expect the STN beta activity to disappear during the execution of phasic motor behaviors of RBD.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: July 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years to 70 Years

Eligibility

Inclusion Criteria:

• Men and women, 35 to 70 years old, with idiopathic PD (UKPDSBB criteria) with motor fluctuations

• having RBD according to the International Classification of Sleep Disorders, 2nd edition (ICSD-2) criteria

• Eligible to neurosurgical treatment of PD by implantation of intracranial electrodes for the DBS of STN

• Giving a written informed consent

• Affiliated to the French social security program

Exclusion Criteria:

• Atypical or secondary parkinsonian syndrome

• Cognitive impairment which may compromise the understanding and patient's participation to the protocol (Mattis dementia rating scale score = 136)

• Patient under guardianship, trusteeship or judicial protection

• Pregnancy or breastfeeding

• Patient participating to another clinical research study in the same period

Related Conditions & MeSH terms

• Mental Disorders
• Parkinson Disease
• REM Sleep Behavior Disorder

Intervention

Other:
• Synchronised video-polysomnography
We will record the electrical activity of the STN (local field potentials) during the 2 consecutive nights following the implantation of the electrodes in the STN for DBS. In this period, the deep brain stimulator will not yet be connected to the intracranial electrodes. The intracranial EEG signal from the STN will be synchronised with the scalp EEG and other video-polysomnographic parameters. The STN recordings during the phasic movements of RBD will be compared to the recordings obtained at the same level during a motor task.

Locations

Country	Name	City	State
France	University Hospital of Purpan	Toulouse	Midi-Pyrénées
France	University Hospital of Rangueil	Toulouse	Midi-Pyrénées

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Toulouse	Grenoble Institut des Neurosciences

Country where clinical trial is conducted

France, 

References & Publications (31)

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De Cock VC, Vidailhet M, Leu S, Texeira A, Apartis E, Elbaz A, Roze E, Willer JC, Derenne JP, Agid Y, Arnulf I. Restoration of normal motor control in Parkinson's disease during REM sleep. Brain. 2007 Feb;130(Pt 2):450-6. — View Citation

Drouin, N., L. Allard, et al. (2011). Sleep staging using Subdermal Wire Electrodes during intracerebral EEG recordings (abstract 1.133). American Epilepsy Society 65th annual meeting. Baltimore, MD., U.S.A.

Fernández-Mendoza J, Lozano B, Seijo F, Santamarta-Liébana E, Ramos-Platón MJ, Vela-Bueno A, Fernández-González F. Evidence of subthalamic PGO-like waves during REM sleep in humans: a deep brain polysomnographic study. Sleep. 2009 Sep;32(9):1117-26. — View Citation

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Iber, C., S. Ancoli-Israel, et al. (2007). The AASM Manual for the Scoring of Sleep and Associated Events. Rules, Terminology and Technical Specifications. Westchester, IL, American Academy of Sleep Medicine.

Kühn AA, Trottenberg T, Kivi A, Kupsch A, Schneider GH, Brown P. The relationship between local field potential and neuronal discharge in the subthalamic nucleus of patients with Parkinson's disease. Exp Neurol. 2005 Jul;194(1):212-20. — View Citation

Levy R, Ashby P, Hutchison WD, Lang AE, Lozano AM, Dostrovsky JO. Dependence of subthalamic nucleus oscillations on movement and dopamine in Parkinson's disease. Brain. 2002 Jun;125(Pt 6):1196-209. — View Citation

Luppi, P. H., O. Clement, et al. (2011).

Marceglia, S., M. Fumagalli, et al. (2011).

Martinez-Martin, P., C. Rodriguez-Blazquez, et al. (2013).

Mena-Segovia J, Bolam JP, Magill PJ. Pedunculopontine nucleus and basal ganglia: distant relatives or part of the same family? Trends Neurosci. 2004 Oct;27(10):585-8. — View Citation

Nishida, N., T. Murakami, et al. (2011).

Oudiette D, Leu-Semenescu S, Roze E, Vidailhet M, De Cock VC, Golmard JL, Arnulf I. A motor signature of REM sleep behavior disorder. Mov Disord. 2012 Mar;27(3):428-31. doi: 10.1002/mds.24044. — View Citation

Rivlin-Etzion M, Marmor O, Heimer G, Raz A, Nini A, Bergman H. Basal ganglia oscillations and pathophysiology of movement disorders. Curr Opin Neurobiol. 2006 Dec;16(6):629-37. Review. — View Citation

Rodriguez-Oroz, M. C., J. Lopez-Azcarate, et al. (2011).

Sixel-Döring, F., E. Trautmann, et al. (2011).

Stefani A, Galati S, Peppe A, Bassi A, Pierantozzi M, Hainsworth AH, Bernardi G, Orlacchio A, Stanzione P, Mazzone P. Spontaneous sleep modulates the firing pattern of parkinsonian subthalamic nucleus. Exp Brain Res. 2006 Jan;168(1-2):277-80. — View Citation

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Urbain N, Gervasoni D, Soulière F, Lobo L, Rentéro N, Windels F, Astier B, Savasta M, Fort P, Renaud B, Luppi PH, Chouvet G. Unrelated course of subthalamic nucleus and globus pallidus neuronal activities across vigilance states in the rat. Eur J Neurosci. 2000 Sep;12(9):3361-74. — View Citation

Urrestarazu E, Iriarte J, Alegre M, Clavero P, Rodríguez-Oroz MC, Guridi J, Obeso JA, Artieda J. Beta activity in the subthalamic nucleus during sleep in patients with Parkinson's disease. Mov Disord. 2009 Jan 30;24(2):254-60. doi: 10.1002/mds.22351. — View Citation

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Weinberger M, Mahant N, Hutchison WD, Lozano AM, Moro E, Hodaie M, Lang AE, Dostrovsky JO. Beta oscillatory activity in the subthalamic nucleus and its relation to dopaminergic response in Parkinson's disease. J Neurophysiol. 2006 Dec;96(6):3248-56. — View Citation

Williams D, Kühn A, Kupsch A, Tijssen M, van Bruggen G, Speelman H, Hotton G, Loukas C, Brown P. The relationship between oscillatory activity and motor reaction time in the parkinsonian subthalamic nucleus. Eur J Neurosci. 2005 Jan;21(1):249-58. — View Citation

* Note: There are 31 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	STN 8-30 Hz mean power	Difference of the mean power of the 8-30 Hz frequency band at the NST during the phasic movements of TCSP and during the execution voluntary movements in the "off" phase.	Outcome measure is assessed during the 2 nights and the two days following the implantation of the electrode in the STN.
Secondary	Difference of the mean power of the 8-13 Hz, 14-30 Hz and 60-90 Hz frequency bands at the NST during the phasic movements of TCSP and during the execution voluntary movements in the "off" phase.		Outcome measures are assessed at days 2 and 3 and nights 1 and 2.
Secondary	Difference of the mean power of the 8-30 Hz and 60-90 Hz frequency bands at the NST during the phasic movements of TCSP and during the execution voluntary movements in the "on" phase.		Outcome measures are assessed at days 2 and 3 and nights 1 and 2.
Secondary	Frequency spectrum at NST REM sleep without atonia and REM sleep with atonia.		Outcome measures are assessed at days 2 and 3 and nights 1 and 2.
Secondary	Frequency spectrum at the NST during non REM sleep (N1, N2 and N3 stages), REM sleep (R) and nocturnal wake.		Outcome measures are assessed at days 2 and 3 and nights 1 and 2