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

Parkinson's Disease Clinical Trial

— DEXPROPAR  

Official title:

Effects of Dexmedetomidine vs Propofol on the Recordings of Deep Brain Activity (Local Field Potentials) Measured Through Implanted Stimulators

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02256319
• Other study ID #: DEXPROPAR
• Status: Completed
• Phase: Phase 4
• First received: September 30, 2014
• Last updated: December 17, 2015
• Start date: September 2014
• Est. completion date: December 2015

Study information

• Verified date: February 2015
• Source: Clinica Universidad de Navarra, Universidad de Navarra
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos SanitariosSpain: Comité Ético de Investigación Clínica
• Study type: Interventional

Clinical Trial 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.

Description:

Comparative clinical trial, non blinded, controlled and sequential, evaluating the effects of propofol and dexmedetomidine in the basal ganglia of PD patients through a DBS electrode.

It is a phase IV clinical trial evaluating the effects of a drug outside the approved.

The study takes part in three phases:

1. DBS placement under sedation with dexmedetomidine at 0.2 μg/kg/h. This will be called "dexmedetomidine record".

2. Four days later and with no sedation, a recording will be registered in one of the specialized electrically isolated rooms at the Neurophysiology Department. This will be dubbed "basal recording". The equipment used is also the standard one used for routine postoperative recordings.

3. 5 days after the initial surgery, and following the protocol in place for these procedures, the tunnelization and battery placement will take place. This is done under general anaesthesia. During anaesthetic induction, the patient is exposed to incremental doses of propofol. Different plasmatic concentrations will be targeted using the mathematical model in the target controlled infusion (TCI) pump. These recordings will be called "propofol at a 0.5, 1, 1.5, 2, 2.5 μg/mL".

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• Dexmedetomidine
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.
• Propofol
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.

Locations

Country	Name	City	State
Spain	University of Navarra Clinic	Pamplona	Navarra

Sponsors (1)

Lead Sponsor	Collaborator
Clinica Universidad de Navarra, Universidad de Navarra

Country where clinical trial is conducted

Spain, 

References & Publications (15)

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. Erratum in: Mov Disord. 2008 Aug 15;23(11):1638. — View Citation

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. Review. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

Rodriguez-Oroz MC, López-Azcárate 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. — View Citation

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, Lo — View Citation

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. — View Citation

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

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. — View Citation

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. — 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

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. Review. — View Citation

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

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	UPDRS-III score	Changes in UPDRS-III score with dexmedetomidine and propofol	2 minutes for each score	No