Pendragon Medical Ltd.Pendragon Medical Ltd.
Technology, Study Results and Device Presentation of the truly non-invasive continuous Glucose Monitor PENDRA
Dr. Thomas W. Schrepfer
Pendragon Medical Ltd.Pendragon Medical Ltd.ContentContent
1)1) Glucose MonitoringGlucose Monitoring
2)2) TechnologyTechnology
3)3) DeviceDevice
4)4) The HypoThe Hypo--WarningWarning
5)5) Clinical TrialsClinical Trials
Pendragon Medical Ltd.Pendragon Medical Ltd.Glucose Glucose MonitoringMonitoring
Glucose Monitoring Glucose Monitoring –– A Major ChallengeA Major Challenge
Spot Measurements vs. Continuous MonitoringSpot Measurements vs. Continuous Monitoring
Hyperglycaemia regionHyperglycaemia region
Hypoglycaemia regionHypoglycaemia region
Hyperglycaemia regionHyperglycaemia regionHyperglycaemia regionHyperglycaemia region
Hypoglycaemia regionHypoglycaemia regionHypoglycaemia regionHypoglycaemia region0
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29 .10 .2001 12 :00 30 .10 .2001 00 :00 30 .10 .2001 12 :00 31 .10 .2001 00 :00
Date / TimeDate / Time
glucoseglucose[mg /dl][mg /dl]
FingerprickFingerprickreadingreading
ContinuousContinuousreadingreading
Pendragon Medical Ltd.Pendragon Medical Ltd.MarketMarket
PresentPresent SolutionsSolutions forfor Glucose Glucose TestingTesting
Traditional Traditional fingerfinger prickprick measurementsmeasurements oror alternatealternatesitesite testingtesting (AST)(AST)
••invasiveinvasive••nonnon--continuouscontinuous••painfulpainful
ContinuousContinuous monitoringmonitoring forfor clinicalclinical useuse••invasiveinvasive••usingusing interstitialinterstitial fluidfluid (ISF)(ISF)••changechange of of measurementmeasurement sitesite everyevery fewfew daysdays••no no realtimerealtime readingsreadings
ContinuousContinuous monitoringmonitoring forfor homehome useuse••minimallyminimally invasiveinvasive••usingusing ISF ISF ••no no realtimerealtime readingsreadings••limitedlimited numbernumber of of readingsreadings••skinskin irritationsirritations
Pendragon Medical Ltd.Pendragon Medical Ltd.TechnologyTechnology
Glucose Monitoring
• Fluid extraction from skin• Interstitial fluid harvesting
FIR SpectroscopyOptical rotation of
polarizied lightUltrasonic +NIR Spectroscopy
Energy
Measure Interaction Calculateglucose concentration
Fluid extractionRadiation
(non-invasive)
Impedance Spectroscopy is different
Pendragon Medical Ltd.Pendragon Medical Ltd.TechnologyTechnology
Impedance Spectroscopy
1010--11 f (Hz)101033101022101000
101055 101066 101077 101088 101099 10101010101044101011 10101111
Tissue LymphocyteErythrocyte
Proteins Water
BoundWater
DNA Lipids
β -Dispersion
Measuring permittivity and conductivity of interfacial polarisation processes in the β -Dispersion
Reference: A. Caduff et al, Biosensors & Bioelectronics 2003; J. Phys. D: Appl. Phys.36 (2003) 369–374.
Pendragon Medical Ltd.Pendragon Medical Ltd.TechnologyTechnology
Impact of glucose on electrolytes
+-
--
-
+
+
+ -- +
+
--
++
-
-
--
Am J Med 1999 Apr;106(4):399-403
133134135136137138139140141142
0 2 4 6 8time [h]
[mm
ol/l]
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Na+ (mmol/L) Glu (mmol/L)
[mm
ol/l]
( ) ( )000
0
ωεωσ
ωεσ
εωε
σεεωε
jjj
** =
′−′=
+′′−′=
Change of apparent dipole moment due to accumulation of ions on membrane
(interfacial polarisation).
Pendragon Medical Ltd.Pendragon Medical Ltd.
Glucose vs Na in patients with Diabetes
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cose
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Sodi
um [m
mol
/l]
BG Sodiumn=15
Pendragon Medical Ltd.Pendragon Medical Ltd.
Cell reaction on D/L-glucoseOne-cell dielectric spectra
D-Glucose concentration dependance
L-Glucose concentration dependance
Reference: Hayashi Y, Livshits L, Caduff A, Feldman Y. Dielectric spectroscopy study of specific glucose influence on human erythrocyte membranes. J Phys D: Appl Phys 36:369-374, 2003
Pendragon Medical Ltd.Pendragon Medical Ltd.TechnologyTechnology
Sensor coupled to skin
Resonantcircuit
coupled to skin
LSensor
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145
30 35 40 45 50 55 60
|Z|
IZImin
fminResonant circuit to measurechanges in Z
L
C R Z
Pendragon Medical Ltd.Pendragon Medical Ltd.TechnologyTechnology
PENDRAPENDRA®® -- SensorSensor
ArmArm
Sensor plateSensor plate
Pendragon Medical Ltd.Pendragon Medical Ltd.
Calibration
time scale (real time and minute of trial)
Measuredparameters Zy
Fx
T1/2
BG
Baseline
terms additionalbaseline +++++= FTTZglu 423121 αααα
at least 5 calibration points needed to define all coefficients α1 to α4
Pendragon Medical Ltd.Pendragon Medical Ltd.
NI-CGMD readings vs BGM
Day 1Day 1--33
Day 4Day 4--66
Day 7Day 7--99
Tsens
Tdev
Fmin
Fmin
BGM
Pendra
Pendragon Medical Ltd.Pendragon Medical Ltd.DeviceDevice
PENDRAPENDRA®®
CE certified as medical device class type II bCE certified as medical device class type II b
Pendragon Medical Ltd.Pendragon Medical Ltd.DeviceDevice
PENDRAPENDRA®®
TheThe devicedevice isis designeddesigned
•• as an as an adjunctiveadjunctive devicedevice to to supplementsupplement bloodblood glucoseglucose measuringmeasuring
•• to to helphelp to to detectdetect trendstrends and and patternspatterns in in glucoseglucose levelslevels
TheThe devicedevice will will helphelp physiciansphysicians to to simplifysimplify thethe controlcontrol of of patientspatients‘‘therapytherapy......
...and ...and thethe patientspatients will will benefitbenefitfromfrom easiereasier selfself--controlcontrol, , whichwhichresultsresults in an in an improvementimprovement of of theirtheirqualityquality of lifeof life
Pendragon Medical Ltd.Pendragon Medical Ltd.DeviceDevice
Glucose StatusGlucose Status
Trend Trend IndicatorIndicator
MeasurementMeasurement IndicatorIndicator
CommunicationCommunicationStatusStatus
MemoryMemoryStatusStatus
Glucose Glucose UnitsUnits
BatteryBatteryStatusStatusTimeTime
AccousticAccousticAlarm Alarm
Glucose Glucose ValuesValues
Time Time Mode Mode
Pendragon Medical Ltd.Pendragon Medical Ltd.TheTheHypoHypo--WarningWarning
Approximation of Future Glucose Approximation of Future Glucose ExcursionExcursionPENDRAPENDRA®® isis PessimisticPessimistic
Glu
cose
G
luco
se level
level
TimeTime
Information Information aboutabout glucoseglucoseslopeslope and and itsits excursionexcursion
LimitingLimiting maximal maximal glucoseglucoseexcursionexcursion to to physiologicalphysiologicalrangerange allowsallows a a worstworst casecasescenarioscenario predictionprediction
Hypo Hypo alarmalarm isis triggeredtriggered ififglucoseglucose levellevel will will bebe underunder a a certaincertain limitlimit afterafter a a defineddefinedtimetime
Pendragon Medical Ltd.Pendragon Medical Ltd.AlarmsAlarms
Alarms Alarms areare TriggeredTriggered in in FollowingFollowingSituationsSituations
I) Parameter extractionI) Parameter extractionRiskRisk of of gettinggetting intointo a a hypoglycaemichypoglycaemic statestate in in nearnearfuturefuture ((withinwithin nextnext 20 min)20 min)
Glucose Glucose valuevalue isis at at oror lowerlower as as thethe givengiven thresholdthreshold forforhypoglycaemia II) First glucose calculationII) First glucose calculationhypoglycaemia
TheThe patientpatient isis moremore thanthan a a certaincertain periodperiod ((e.ge.g. 30 min.) in a . 30 min.) in a hyperglycaemichyperglycaemic conditioncondition
III) Corrections and alarmsIII) Corrections and alarmsRapid inRapid in-- oror decreasedecrease of of bloodbloodglucoseglucose
Pendragon Medical Ltd.Pendragon Medical Ltd.DeviceDevice
Pendragons’Pendragons’ SSolution for olution for CContinuous ontinuous NNonon--invasive invasive MMonitoring of onitoring of GGlucoselucose (1)(1)
Truly nonTruly non--invasiveinvasive continuouscontinuous realtimerealtime measurementmeasurementss
MeasurementMeasurement frequencyfrequency of 1 per of 1 per minuteminute –– dayday and and nightnight
AdjustableAdjustable alert alert forfor upcomingupcoming hypoglycaemichypoglycaemic conditionsconditionsand and forfor hyperglycaemichyperglycaemic situationssituations
TTrend indicatrend indicatoror for changes of glucosefor changes of glucose
Physician software Physician software forfor patiepatientnt datadata managementmanagement
Patient Patient softwaresoftware to to visualizevisualize glucoseglucose excursionsexcursions
Storage capacity of 1 monthStorage capacity of 1 month
Pendragon Medical Ltd.Pendragon Medical Ltd.DeviceDevice
Pendragons’Pendragons’ SSolution for olution for CContinuous ontinuous NNonon--invasive invasive MMonitoring of onitoring of GGlucoselucose (2)
NNo blood sample or interstitial fluido blood sample or interstitial fluid neededneeded
No No needneed of of expensiveexpensive disposablesdisposables
OffersOffers physiciansphysicians and and patientspatients thethe possibilitypossibility ofof tighter tighter control control of of glucoseglucose
Helps to simplify the therapy management (acute and long Helps to simplify the therapy management (acute and long term)term)
ReductionReduction of of diabetesdiabetes complicationscomplications byby continuouscontinuous monitoringmonitoringand and managementmanagement of of hypohypo-- and and hyperglycaemichyperglycaemic conditionsconditions
Pendragon Medical Ltd.Pendragon Medical Ltd.ClinicalClinicalTrialsTrials
Clinical TrialsClinical Trials
Some impressionsSome impressions
Pendragon Medical Ltd.Pendragon Medical Ltd.Results
1. Clinical Experimental Hyper/Hypo Study
Glucose-clamp study
15 patients with diabetes type 1 • Age 27 ± 5.7• Body mass index 23.1 ± 2.3kg/ m2
• HbA1C 6.9 ± 0.8 %
BG kept constant at three different target levels (45, 100, 200 mg/dl) for at least 30 min at each level.
Venous BG was measured by a standard laboratory system
Haematology parameters were measured by BGA.
The raw glucose sensor signals recorded (frequency, impedance) were corrected for temperature and calibrated with reference values from each BG level.
Pendragon Medical Ltd.Pendragon Medical Ltd.Results
Glucose profile
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Glu
cose
[mg/
dl]
45 mg/dl 45 mg/dl
Pendragon Medical Ltd.Pendragon Medical Ltd.Results
Glucose vs Sodium in Patients with Diabetes
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dl]
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Sodi
um [m
mol
/l]
BG Sodiumn=15
Pendragon Medical Ltd.Pendragon Medical Ltd.Results
Clarke Error Grid Analysis
Corresponding Clarke Error Grid analysis:81% in zone A15% in zone B4% in zone D
Correlation coefficient: 0.932
SEP 19.5 mg/dl.
Ref.: A. Caduff, R. Dewarrat, S. Buschor, T. Schrepfer, T. Heise, L. Heinemann, IDF Conference 2003
Pendragon Medical Ltd.Pendragon Medical Ltd.ClinicalClinicalTrialsTrials
2. Results2. Results of a of a clinicalclinical experimental experimental trialtrial
Comparison BGM vs. PENDRAComparison BGM vs. PENDRA®®
15 Patients with diabetes15 Patients with diabetes
ClampClamp--Study by means of a Study by means of a BiostatorBiostator®®
GlucoseGlucose--profile:profile:
9090 9090
250250
2h2h 1h1h 2h2h
ResultsResults::
A 81%, B 18%, D 1%, A 81%, B 18%, D 1%, correlation coefficient: 0.958correlation coefficient: 0.958
PE
ND
RA
PE
ND
RA
®®
ComparativeComparative BG (mg/dl)BG (mg/dl)
Clark Error GridClark Error Grid
Pendragon Medical Ltd.Pendragon Medical Ltd.ClinicalClinicalTrialsTrials
3. Results3. Results of an of an OutpatientOutpatient TrialTriala) Retrospective Analysis of Dataa) Retrospective Analysis of Data
Comparison BGM vs. PENDRAComparison BGM vs. PENDRA®®
15 15 PatientsPatients withwith diabetesdiabetes
2 2 daysdays of of inhouseinhouse trainingtraining
7 7 daysdays of of homehome useuse, 24h/d, 24h/d
7 7 –– 10 BG 10 BG readingsreadings per per dayday
ComparativeComparative BG (mg/dl)BG (mg/dl)
PE
ND
RA
PE
ND
RA
®®Clark Error Clark Error GridGrid
ResultsResults::
A 83%, B 15%, D 2%, A 83%, B 15%, D 2%, correlation coefficient: 0.923correlation coefficient: 0.923
Pendragon Medical Ltd.Pendragon Medical Ltd.ClinicalClinicalTrialsTrials
b) Real Time Values
Comparison BGM vs. PENDRAComparison BGM vs. PENDRA®®
15 15 PatientsPatients withwith diabetesdiabetes
2 2 daysdays of of inhouseinhouse trainingtraining
7 7 daysdays of of homehome useuse, 24h/d, 24h/d
7 7 –– 10 BG 10 BG readingsreadings per per dayday
ResultsResults::A 56%, B 37%, C,D,E 7%, A 56%, B 37%, C,D,E 7%, correlation coefficient: correlation coefficient: 0.6400.640
Pendragon Medical Ltd.Pendragon Medical Ltd.
c) Real-Time Tracking of Blood Glucose Profiles with PENDRA
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online reference
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online reference
Pendragon Medical Ltd.Pendragon Medical Ltd.DeviceDevice
PENDRAPENDRA®® helpshelps patientspatients in in criticalcritical situationssituations
DuringDuring nightnight
LivingLiving alonealone
DuringDuring workwork (stress (stress relatedrelated hypo‘shypo‘s))
DuringDuring carcar drivingdriving
PENDRAPENDRA®® ImprovesImproves QualityQuality of Lifeof Life