Dexmedetomidine vs Propofol on the Recordings of Deep Brain Activity Measured Through Implanted Stimulators

NCT02256319 | Completed Phase 4 DMC

• 1 other identifier: DEXPROPAR
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial has been designed to study and compare changes in deep brain activity (field potentials) in Parkinson's disease (PD) patients while awake, and during sedation with dexmedetomidine or propofol. The recording is made through a deep brain stimulation (DBS) electrode implanted for PD management. The investigators hypothesize that dexmedetomidine produces fewer changes as compared to propofol, and that those changes are consistent and recognizable when compared to activity in patients not exposed to any sedation. Typification of those changes would in the future allow for patients to undergo this surgery comfortably while not compromising the quality of the recording and of the final clinical outcome. The principal variable analyzed is the signal's power in each of the frequency bands, absolute and relative. The analysis will include usual clinical methods such as rapid Fourier transform (FFT) and window fast Fourier transform (WFFT), wavelet analysis, Gabor, and coherence.

Conditions

Parkinson's Disease

Keywords

Deep brain stimulation; Dexmedetomidine; Propofol

Outcome Measures

Primary Outcomes (1)

• Signal power of the local field potentials.

  Signal power separated in bandwidth (theta, slow beta, fast beta, gamma, high frequency); absolute and relative. The comparison will be made between the different measurements: dexmedetomidine, basal and propofol.

  5 minutes for each record

Secondary Outcomes (1)

• UPDRS-III score

  2 minutes for each score

Study Arms (3)

Dexmedetomidine recording

EXPERIMENTAL

Recording registered through the deep brain stimulation electrodes with dexmedetomidine at 0.2 μg/kg/h.

Drug: Dexmedetomidine

Propofol recording

ACTIVE COMPARATOR

Recording registered through the deep brain stimulation electrodes with propofol at plasmatic levels of 0.5, 1, 1.5, 2, 2.5 μg/mL.

Drug: Propofol

Basal recording

NO INTERVENTION

Recording registered through the deep brain stimulation electrodes with no sedation .

Interventions

Dexmedetomidine DRUG

Patients will receive a loading dose of 1 µg/kg in 10 min before starting the surgery. The maintenance dose will be 0.2-1 µg/kg/h for a Ramsey Sedation Score of 3-4 during the surgery´s preparation. It will be reduced to 0.2 µg/kg/h 15 min before starting the microelectrode recording for a Ramsey Sedation Score of 2. After the placement of the deep brain stimulator we will record the local field potentials activity. In addition, the subscales of rigidity, tremor and bradykinesia of the Unified Parkinson's Disease Rating Scale (UPDRS-III) score will be evaluated. Once the deep brain stimulator recording and neurologic exploration will be over patients will receive a maintenance dose 0.2-1 µg/kg/h until the end of the surgery. It will be stopped to transfer the patient to the ICU.

Also known as: (S)-4-[1-(2,3-Dimethylphenyl)ethyl]-3H-imidazole

Dexmedetomidine recording

Propofol DRUG

The target doses are 0.5, 1, 1.5, 2 and 2.5 µg/kg. For its administration we will use the TCI (target controlled infusion) system. After programming each dose we will wait until the plasma and brain concentration of propofol are stabilized in this target and then we will record the local field potentials activity through the DBS. In addition, the subscales of rigidity, tremor and bradykinesia of the UPDRS-III score will be evaluated.

Also known as: 2,6-diisopropylphenol

Propofol recording

Eligibility Criteria

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

You may qualify if:

• Capacity to understand, consent and commit for the three phases of the study.
• Older than 18 years old.
• The patient is scheduled for DBS electrode placement for PD treatment by his neurologist.

You may not qualify if:

• Allergy or hypersensibility to dexmedetomidine or propofol
• Cardiac blockade (types 2 and 3) without an implanted pacemaker
• Low blood pressure (mean \< 60 mmHg) or symptoms of low cardiac output.
• Severe cerebrovascular disease.
• Pregnancy or nursing mothers.

Sponsors & Collaborators

• Clinica Universidad de Navarra, Universidad de Navarra: lead

Study Sites (1)

University of Navarra Clinic

Pamplona, Navarre, 31008, Spain

Location

Related Publications (15)

• Krack P, Batir A, Van Blercom N, Chabardes S, Fraix V, Ardouin C, Koudsie A, Limousin PD, Benazzouz A, LeBas JF, Benabid AL, Pollak P. Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson's disease. N Engl J Med. 2003 Nov 13;349(20):1925-34. doi: 10.1056/NEJMoa035275.

  PMID: 14614167 BACKGROUND

• Hamani C, Richter E, Schwalb JM, Lozano AM. Bilateral subthalamic nucleus stimulation for Parkinson's disease: a systematic review of the clinical literature. Neurosurgery. 2005 Jun;56(6):1313-21; discussion 1321-4. doi: 10.1227/01.neu.0000159714.28232.c4.

  PMID: 15918948 BACKGROUND

• Poon CC, Irwin MG. Anaesthesia for deep brain stimulation and in patients with implanted neurostimulator devices. Br J Anaesth. 2009 Aug;103(2):152-65. doi: 10.1093/bja/aep179. Epub 2009 Jun 25.

  PMID: 19556271 BACKGROUND

• Sassi M, Zekaj E, Grotta A, Pollini A, Pellanda A, Borroni M, Pacchetti C, Menghetti C, Porta M, Servello D. Safety in the use of dexmedetomidine (precedex) for deep brain stimulation surgery: our experience in 23 randomized patients. Neuromodulation. 2013 Sep-Oct;16(5):401-6; discussion 406. doi: 10.1111/j.1525-1403.2012.00483.x. Epub 2012 Jul 10.

  PMID: 22780449 BACKGROUND

• Rozet I, Muangman S, Vavilala MS, Lee LA, Souter MJ, Domino KJ, Slimp JC, Goodkin R, Lam AM. Clinical experience with dexmedetomidine for implantation of deep brain stimulators in Parkinson's disease. Anesth Analg. 2006 Nov;103(5):1224-8. doi: 10.1213/01.ane.0000239331.53085.94.

  PMID: 17056959 BACKGROUND

• Reck C, Florin E, Wojtecki L, Krause H, Groiss S, Voges J, Maarouf M, Sturm V, Schnitzler A, Timmermann L. Characterisation of tremor-associated local field potentials in the subthalamic nucleus in Parkinson's disease. Eur J Neurosci. 2009 Feb;29(3):599-612. doi: 10.1111/j.1460-9568.2008.06597.x. Epub 2009 Jan 28.

  PMID: 19187268 BACKGROUND

• Rodriguez-Oroz MC, Lopez-Azcarate J, Garcia-Garcia D, Alegre M, Toledo J, Valencia M, Guridi J, Artieda J, Obeso JA. Involvement of the subthalamic nucleus in impulse control disorders associated with Parkinson's disease. Brain. 2011 Jan;134(Pt 1):36-49. doi: 10.1093/brain/awq301. Epub 2010 Nov 8.

  PMID: 21059746 BACKGROUND

• Urrestarazu E, Iriarte J, Alegre M, Clavero P, Rodriguez-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.

  PMID: 18951542 BACKGROUND

• Rodriguez-Oroz MC, Obeso JA, Lang AE, Houeto JL, Pollak P, Rehncrona S, Kulisevsky J, Albanese A, Volkmann J, Hariz MI, Quinn NP, Speelman JD, Guridi J, Zamarbide I, Gironell A, Molet J, Pascual-Sedano B, Pidoux B, Bonnet AM, Agid Y, Xie J, Benabid AL, Lozano AM, Saint-Cyr J, Romito L, Contarino MF, Scerrati M, Fraix V, Van Blercom N. Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up. Brain. 2005 Oct;128(Pt 10):2240-9. doi: 10.1093/brain/awh571. Epub 2005 Jun 23.

  PMID: 15975946 RESULT

• Venkatraghavan L, Manninen P. Anesthesia for deep brain stimulation. Curr Opin Anaesthesiol. 2011 Oct;24(5):495-9. doi: 10.1097/ACO.0b013e32834a894c.

  PMID: 21772140 RESULT

• Venkatraghavan L, Luciano M, Manninen P. Review article: anesthetic management of patients undergoing deep brain stimulator insertion. Anesth Analg. 2010 Apr 1;110(4):1138-45. doi: 10.1213/ANE.0b013e3181d2a782. Epub 2010 Feb 8.

  PMID: 20142347 RESULT

• Raz A, Eimerl D, Zaidel A, Bergman H, Israel Z. Propofol decreases neuronal population spiking activity in the subthalamic nucleus of Parkinsonian patients. Anesth Analg. 2010 Nov;111(5):1285-9. doi: 10.1213/ANE.0b013e3181f565f2. Epub 2010 Sep 14.

  PMID: 20841416 RESULT

• Steigerwald F, Hinz L, Pinsker MO, Herzog J, Stiller RU, Kopper F, Mehdorn HM, Deuschl G, Volkmann J. Effect of propofol anesthesia on pallidal neuronal discharges in generalized dystonia. Neurosci Lett. 2005 Oct 7;386(3):156-9. doi: 10.1016/j.neulet.2005.06.012.

  PMID: 16024174 RESULT

• Rozet I. Anesthesia for functional neurosurgery: the role of dexmedetomidine. Curr Opin Anaesthesiol. 2008 Oct;21(5):537-43. doi: 10.1097/ACO.0b013e32830edafd.

  PMID: 18784476 RESULT

• Elias WJ, Durieux ME, Huss D, Frysinger RC. Dexmedetomidine and arousal affect subthalamic neurons. Mov Disord. 2008 Jul 15;23(9):1317-20. doi: 10.1002/mds.22080.

  PMID: 18442130 RESULT

MeSH Terms

Conditions

Parkinson Disease

Interventions

Dexmedetomidine; Propofol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Martínez S Antonio, Doctor

  Staff of the deparment of Anestesiology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2014
• First Posted: October 3, 2014
• Study Start: September 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 18, 2015

Record last verified: 2015-02

Locations

ES (1)