eeg awareness weeks - what eeg can co for your trial
DESCRIPTION
The webinar is directed toward all clinical trial professionals who work on the development of CNS-active drugs and plan a new early or late phase clinical trial. Electroencephalography (EEG), including Event-Related Potentials (ERP), can be an objective endpoint of choice in many cases – this webinar will make clear why, when and with what benefit. Contents: Main EEG paradigms and endpoints Brain disorders and drug action as seen in the EEG The key-lock principle PD/PK modeling with EEG EEG topographies How The Siesta Group can support clinical trial EEGTRANSCRIPT
www.thesiestagroup.com
The Siesta Group WebinarThe Siesta Group Webinar
What EEG can do for your trial
Georg DorffnerP t A dPeter Anderer
Electroencephalography (EEG)
International 10/20 systemInternational 10/20 system
4 minutes eacheyes open/eyes closedy p yRepeated stimuliLong-term (e.g. sleep)
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Stimuli for event-related potentials
Visual (VEP) Acoustic (AEP)Visual (VEP)e.g. checker pattern
Acoustic (AEP)e.g. oddballparadigmparadigm
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Core paradigms of Pharmaco-EEG
Single channel topography tomography(LORETA)
pect
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sis
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-2
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1
2
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t-val
ues
elat
edia
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N1-LATENCY
P2-LATENCY
N2-LATENCY
P300-LATENCY
Eve
nt-re
Pot
nt(E
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E
Main endpoints: qEEG
Power per bandAbsolute and relativeDominant frequenciesfrequenciesratios
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Main endpoints: ERP
LatencyAmplitudeN1 N2 P2N1, N2, P2, P3 componentscomponents
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Why EEG?
It‘s an objective measurement
It helps you answer questions likeIs my drug active in the brain?How does it act?Where does it act?When does it act?At which dose does it act?
7in a very cost-efficient manner
How …
stimulant sedative
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Drug induced EEG changes are related toDrug-induced EEG changes are related to behavioral changes (Fink 1964)
EEG slow activity (with or ith t lit d )
Perceptual discrimination , motor activity , mood , th ht i t it d t without amplitude )
EEG beta activity (with
thought intensity and rate , recall sleep duration , affect , fear y (
amplitude )EEG beta activity (with amplitude )
and anxiety mood , perception of stimuli
amplitude )EEG beta + slow activity delirium, perceptual acuity +
recall , psychomotor tl
EEG alpha activity restlessness relaxation, reveries, pleasant fantasies, feelings of well-being,
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euphoria, mood
How:How: Effect on perception and cognition
10
20
10
0
10
n m
s
30
-20
-10
Diff
erec
nes
in MID (n=16,16)SDAT (n=18,17)
Nicergoline
50
-40
-30
* p<0 05 t-test
*
**
Nicergoline (8 weeks, 20x30mg) vs. Placebo
Shortening of latency points toward cognitive
-50N1 P2 N2 P300
p<0.05 t test** p<0.01
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Shortening of latency points toward cognitiveimprovement
Where … (electrode)
Topographic map(19 l t d(19 electrodes, interpolated)Depicts changes (drug/placebo) or significance (p values)Univariate or several variables
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Where … (brain area): LORETA
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When …
Riba et al. 2002
13PK/PD modeling
At which dose …
DIFFERENCES BETWEEN DRUG ANDDIFFERENCES BETWEEN DRUG-AND PLACEBO-INDUCED CHANGES IN ABSULUTE POWER VARIABLES AFTER 0.1mg, 0.2 mg AND 0.4mg SURICLONE AND 1mg ALPRAZOLAM 2 g gHOURS AFTER ORAL ADMINSTRATION (N=15)
Saletu et al 1994
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Saletu et al, 1994
Cost-effectiveness
15Wilson 2012
Other advantages
UnobtrusiveUnobtrusiveNo radiation or additional exposure to drugsethically without problemsShort measurement without too many yburdensEffects with n = 10 .. 40Effects with n 10 .. 40
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Key-Lock Principle (Saletu)
Representative drugs of the main h h l i l l i dpsychopharmacological classes induce – as
compared to placebo – significant and typical h i th EEGchanges in the EEG
In many variables these changes are opposite to differences between patients pp psuffering from mental disorders
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18Saletu et al. 2006
19Saletu et al. 2006
Key-lock – example
Saletu et al. 1997
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EEG in the development cycle
Dose-efficacy relationsPreclinical Therapeutic outcome
Relation to clinical
Preclinical
variables
R d t EEGPhase I
Rodent EEGRodent sleepTranslationalhypotheses
Phase II
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yp
Data quality
EEG is a very sensitive instrument
Data quality must be high and constantq y gProper patchingProper devicesProper devicesAvoidance of artifactsSubject must be awakeSubject must be awakeNo disturbance
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Artifacts - example
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Artifact after reduction
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The Siesta Group
Clinical trial service provider specialised in sleep and/or Electroencephalography (EEG)Large scientific background, physician co-ownedp yTight network of partners and associatesHeadquarter :Headquarter :Vienna, Austria, EuropeUS operations through Philips-RespironicsRespironics
Developer of Somnolyzer24x7,purchased by Philips Respironics
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purchased by Philips-Respironics, Feb 2010
Pharmaco-EEG: Services we offer
Consulting and protocol developmentTrial feasibility and set-upSite identification, preparation, training, managementp p g gCentralized data analysis, such as sleep scoring, EEG spectral analysis, and other endpoint calculationPSG and EEG data quality monitoring and harmonizationBiomarker research and exploratory data analysisDevice rentals
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Pharmaco-EEG: Our strengths
Covering full spectrum of pharmaco-EEGHigh level quality controlg q ySuperior artefact treatment>30 years of experience>30 years of experienceState-of-the-art technologyTop experts in psychiatry and neurologyFollowing latest IPEG standards
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g
Scoring/Reading center – data flow
Sponsor Endpoint variabletable
SiestaCRF
S esta
reports
PSG/EEG data (edf)Online SDex
reports
Inv. siteInv. site
Inv. siteInv site
Secure ftpMain variables
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Inv. site
Special offer for US trials:Special offer for US trials:Partnership with Community Research
Dedicated Clinical Research Site (Since 1995)Th L ti i G t Ci i ti OHThree Locations in Greater Cincinnati, OH60 Bed Phase 1 Unit Located on Hospital CampusPhase 1 Experience Includes: First-in-Human, SAD/MAD, Patient/Special Populations Food Effect EEG/PSG VaccinesPopulations, Food Effect, EEG/PSG, Vaccines18 Year History of Excellence in Sleep Research8 Bed Sleep Laboratory in Phase 1 Unit; (14 total PSG beds)Sl St di I l d I i N l Sl A R tl LSleep Studies Include: Insomnia, Narcolepsy, Sleep Apnea, Restless Leg Syndrome, Shift Work Sleep Disorder, Non-Restorative Sleep Syndrome, Jet Lag, Sleep and Human PerformanceRecruitment Database of 60 000 NHV and Patient PopulationsRecruitment Database of 60,000 NHV and Patient PopulationsCNS Populations: Depression, Bipolar, GAD, OCD, Binge Eating, Alzheimer's Disease, Parkinson's Disease, Pain (Chronic, OA/RA, Fibromyalgia, Migraine)
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y g g )Excellent Inspection History: 3 FDA Audits Without 483 Findings
Your advantage
EEG expertise, investigator, and trial manager in onemanager in oneUtmost quality through joint SOPsReduced costs and quicker study startCombined experience in almost every field of p yCNS-active drugs
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Our offer until March 31, 2013
Free Feasibility: C t d ff t f i l di EEGCosts and efforts for including EEG
You provide: real or mock protocolYou provide: real or mock protocol
W id t ti t f dditi lWe provide: a cost estimate for additional EEG costs
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Contact
The Siesta GroupVienna Austria:Vienna, Austria:Phone: +43 1 [email protected]@ g pwww.thesiestagroup.com
USA: Philips RespironicsBend, Oregon:Phone: 1-541-598-3800, [email protected] respironics com
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clinicaltrials.respironics.com
References
Riba J, Anderer P, Morte A, Urbano G, Jané F, Saletu B, Barbanoj MJ.: Topographic pharmaco-EEG mapping of the effects of the South American
h ti b h i h lth l t B J Cli Ph lpsychoactive beverage ayahuasca in healthy volunteers. Br J Clin Pharmacol. 2002 Jun;53(6):613-28.Saletu B, Anderer P, Saletu-Zyhlarz GM.: EEG topography and tomography (LORETA) in the classification and evaluation of the pharmacodynamics of(LORETA) in the classification and evaluation of the pharmacodynamics of psychotropic drugs. Clin EEG Neurosci. 2006 Apr;37(2):66-80.Saletu B, Saletu-Zyhlarz G, Anderer P, Brandstätter N, Frey R, Gruber G, Klösch G, Mandl M, Grünberger J, Linzmayer L.: Nonorganic insomnia in , , g , y ggeneralized anxiety disorder. 2. Comparative studies on sleep, awakening, daytime vigilance and anxiety under lorazepam plus diphenhydramine(Somnium) versus lorazepam alone, utilizing clinical, polysomnographic and EEG mapping methods Neuropsychobiology 1997;36(3):130 52EEG mapping methods. Neuropsychobiology. 1997;36(3):130-52.Saletu B, Grünberger J, Linzmayer L, Semlitsch HV, Anderer P, Chwatal K.: Pharmacokinetic and -dynamic studies with a new anxiolytic, suriclone, utilizing EEG mapping and psychometry Br J Clin Pharmacol 1994 Feb;37(2):145-56
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EEG mapping and psychometry. Br J Clin Pharmacol. 1994 Feb;37(2):145 56.