Pendragon Medical Ltd. | PENDRA

Pendragon Medical
Medical Ltd.
Ltd.
Pendragon
Technology, Study Results and Device
Presentation of the truly non-invasive
continuous Glucose Monitor PENDRA
Dr. Thomas W. Schrepfer
Pendragon Medical
Medical Ltd.
Ltd.
Pendragon
Content
1) Glucose Monitoring
2) Technology
3) Device
4) The Hypo-Warning
5) Clinical Trials
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Glucose
Monitoring
Glucose Monitoring – A Major Challenge
Spot Measurements vs. Continuous Monitoring
glucose
[mg /dl]
300
Hyperglycaemia region
250
200
150
100
50
0
29.10.2001 12:00
Hypoglycaemia region
30.10.2001 00:00
30.10.2001 12:00
Date / Time
31.10.2001 00:00
Fingerprick
reading
Continuous
reading
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Medical Ltd.
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Market
Present Solutions for Glucose Testing
Traditional finger prick measurements or alternate
site testing (AST)
•invasive
•non-continuous
•painful
Continuous monitoring for clinical use
•invasive
•using interstitial fluid (ISF)
•change of measurement site every few days
•no realtime readings
Continuous monitoring for home use
•minimally invasive
•using ISF
•no realtime readings
•limited number of readings
•skin irritations
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Technology
Glucose Monitoring
Radiation
(non-invasive)
Fluid extraction
• Fluid extraction from skin
• Interstitial fluid harvesting
FIR Spectroscopy
Optical rotation of
polarizied light
Energy
Ultrasonic +NIR Spectroscopy
Impedance Spectroscopy
is different
Measure Interaction ÆCalculate
glucose concentration
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Technology
Impedance Spectroscopy
10-1 10
0
101
102
103
104
105
106
107
108
109
β -Dispersion
Bound
Water
Proteins
Tissue
DNA
Lymphocyte
Erythrocyte
1010
1011
Water
Lipids
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.
f (Hz)
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Technology
142
141
140
139
138
137
136
135
134
133
-
25
20
15
10
5
0
8
6
4
time [h]
Na+ (mmol/L)
Glu (mmol/L)
2
[mmol/l]
[mmol/l]
Impact of glucose on electrolytes
-
0
-
Am J Med 1999 Apr;106(4):399-403
+ - + +
+ +
+
+
- - +
Change of apparent dipole moment due to
accumulation of ions on membrane
(interfacial polarisation).
*


′
σ
(
σ
σ
ω)
*
0 

ε (ω) = ε ′ − jε ′′ +
= ε′ − j
=

ε0ω 
ωε0 jωε0

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Glucose vs Na in patients with Diabetes
145
250
Glucose [mg/dl]
141
150
139
100
137
50
135
0
133
0
n=15
2
4
6
8
Time [h]
BG
10
Sodium
12
14
16
Sodium [mmol/l]
143
200
Pendragon Medical
Medical Ltd.
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Cell reaction on D/L-glucose
One-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
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Medical Ltd.
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Technology
Sensor coupled to skin
Sensor
L
Resonant
circuit
coupled to skin
145
140
135
130
125
L
120
C
R
115
Z
|Z|
IZImin
110
105
100
Resonant circuit to measure
changes in Z
30
35
fmin
40
45
50
55
60
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Technology
PENDRA® - Sensor
Arm
Sensor plate
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Calibration
BG
T1/2
Measured
parameters
Baseline
Zy
Fx
time scale (real time and minute of trial)
glu = baseline + α 1 Z + α 2T1 + α 3T2 + α 4 F + additional terms
at least 5 calibration points needed to define all coefficients α1 to α4
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NI-CGMD readings vs BGM
Tsens
Tdev
Day 1-3
Fmin
Fmin
Pendra
BGM
Day 4-6
Day 7-9
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Device
PENDRA®
CE certified as medical device class type II b
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Medical Ltd.
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Device
PENDRA®
The device is designed
• as an adjunctive device to supplement blood glucose measuring
• to help to detect trends and patterns in glucose levels
The device will help physicians to
simplify the control of patients‘
therapy...
...and the patients will benefit
from easier self-control, which
results in an improvement of their
quality of life
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Device
Measurement Indicator
Communication
Status
Glucose Status
Memory
Status
Trend
Indicator
Glucose
Units
Accoustic
Alarm
Battery
Status
Time
Glucose
Values
Time
Mode
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Approximation of Future Glucose Excursion
PENDRA® is Pessimistic
Information about glucose
slope and its excursion
Limiting maximal glucose
excursion to physiological
range allows a worst case
scenario prediction
Glucose level
The
HypoWarning
Hypo alarm is triggered if
glucose level will be under a
certain limit after a defined
time
Time
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Alarms
Alarms are Triggered in Following
Situations
Risk of getting into a
hypoglycaemic state in near
future (within next 20 min)
Glucose value is at or lower as
the given threshold for
hypoglycaemia
I) Parameter extraction
II) First glucose calculation
The patient is more than a
certain period (e.g. 30 min.) in a
hyperglycaemic condition
Rapid in- or decrease of blood
glucose
III) Corrections and alarms
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Medical Ltd.
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Device
Pendragons’ Solution for Continuous Noninvasive Monitoring of Glucose (1)
Truly non-invasive continuous realtime measurements
Measurement frequency of 1 per minute – day and night
Adjustable alert for upcoming hypoglycaemic conditions
and for hyperglycaemic situations
Trend indicator for changes of glucose
Physician software for patient data management
Patient software to visualize glucose excursions
Storage capacity of 1 month
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Medical Ltd.
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Device
Pendragons’ Solution for Continuous
Non-invasive Monitoring of Glucose (2)
No blood sample or interstitial fluid needed
No need of expensive disposables
Offers physicians and patients the possibility of tighter
control of glucose
Helps to simplify the therapy management (acute and long
term)
Reduction of diabetes complications by continuous monitoring
and management of hypo- and hyperglycaemic conditions
Clinical
Trials
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Clinical Trials
Some impressions
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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.
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Results
Glucose profile
Glucose [mg/dl]
250
200
150
100
50
0
45 mg/dl
0
1
2
45 mg/dl
3
4
Time [h]
5
6
7
Pendragon Medical
Medical Ltd.
Ltd.
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Results
Glucose vs Sodium in Patients with Diabetes
145
250
Glucose [mg/dl]
141
150
139
100
137
50
135
0
133
0
2
n=15
4
6
8
Time [h]
BG
10
Sodium
12
14
16
Sodium [mmol/l]
143
200
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Medical Ltd.
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Results
Clarke Error Grid Analysis
Corresponding Clarke Error
Grid analysis:
81% in zone A
15% in zone B
4% 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
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2. Results of a clinical experimental trial
Clark Error Grid
Comparison BGM vs. PENDRA®
15 Patients with diabetes
Clamp-Study by means of a
Biostator®
Glucose-profile:
PENDRA®
Clinical
Trials
250
90
2h
90
1h
2h
Results:
Comparative BG (mg/dl)
A 81%, B 18%, D 1%,
correlation coefficient: 0.958
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3. Results of an Outpatient Trial
a) Retrospective Analysis of Data
Clark Error Grid
Comparison BGM vs. PENDRA®
15 Patients with diabetes
2 days of inhouse training
7 days of home use, 24h/d
PENDRA®
Clinical
Trials
7 – 10 BG readings per day
Results:
Comparative BG (mg/dl)
A 83%, B 15%, D 2%,
correlation coefficient: 0.923
Clinical
Trials
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b) Real Time Values
Comparison BGM vs. PENDRA®
15 Patients with diabetes
2 days of inhouse training
7 days of home use, 24h/d
7 – 10 BG readings per day
Results:
A 56%, B 37%, C,D,E 7%,
correlation coefficient:
0.640
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c) Real-Time Tracking of Blood Glucose Profiles with
PENDRA
EO102
EE107
400
500
350
450
400
300
350
250
300
online
200
reference
200
150
150
100
100
50
0
01.12.2002
12:00
250
50
01.12.2002
18:00
02.12.2002
00:00
02.12.2002
06:00
0
04.12.2002 12:00 04.12.2002 18:00 05.12.2002 00:00 05.12.2002 06:00
online
reference
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Device
PENDRA® helps patients in critical situations
During night
Living alone
During work (stress related hypo‘s)
During car driving
PENDRA® Improves Quality of Life