Diabetes Research in Children Network Pilot Study of the NavigatorTM

Continuous Glucose Monitoring Systemin Children with Type 1 Diabetes:

Safety, Tolerability, andFactors Associated with Use

Stuart A Weinzimer, MDfor the

Diabetes Research in Children Network Study Group26 Oct 2007

New Haven, CT

Background

• Real-time continuous glucose monitoring devices (CGM) are a potentially powerful tool in the management of type 1 diabetes (T1D)

• For successful adoption into clinical practice, however, they must be accurate, comfortable to wear, and easy to use, particularly in children

• A previous-generation CGM, the GlucoWatch Biographer, failed to improve glycemic control in 200 children with T1D during a 6-mth trial

Objectives

• The aims of this pilot study were to examine the tolerability and effectiveness of a continuous glucose monitor (Abbott Navigator) in children with type 1 diabetes using intensive insulin regimens– CSII (insulin pump therapy)– Glargine-based multiple daily injection (MDI)

• To identify demographic and/or clinical factors predictive of successful long-term use of CGM

Study Design

• Subjects wore the Navigator as an outpatient for 1 week but were blinded to sensor data in order to characterize “baseline” control

• Subjects wore the Navigator (unblinded) as an outpatient for 13 weeks

• Devices were downloaded weekly to subjects’ home computers and subjects were contacted frequently (q1-4wk) in order to monitor Navigator use

• CGM Satisfaction questionnaires were completed at baseline and 13 weeks

• Subjects then invited to continue use of Navigator for additional 13 weeks

Outcome Measures

• Glycemic control

– Hemoglobin A1c– Mean glucose levels– Percentage of glucose values within, above, or

below target

• Glycemic variability

– Mean amplitude of glycemic excursion (MAGE)

• Tolerability

– Continuous Glucose Satisfaction Scale

• Measures interstitial glucose levels

• Requires calibration using fingerstick blood glucose at 10, 12, 24 and 72 hours after insertion

• After a 10-hr warm-up, provides glucose readings every 60 seconds for up to 120 hours

• Operating range 20 - 500 mg/dL

• Displays a trend arrow indicating glucose rate of change

• Alarms for actual or impending high or low glucose levels

Abbott NavigatorTM

Study Subjects – Phase II

CSII MDI p-value

N (13-week Phase) 30 27

N (extension to 26 wk) 24 21

Age (y) 11.1 ± 3.7 10.3 ± 3.7 0.62

Female 8 (33%) 10 (48%) 0.37

T1D duration (y) 6.1 ± 3.3 3.5 ± 1.8 0.005

HbA1c (%) 7.1 ± 0.7 7.8 ± 0.9 0.01

Mean Glucose (mg/dL) 178 ± 27 190 ± 33 0.14

MAGE (mg/dL) 126 ± 32 151 ± 44 0.06

0

40

80

120

160

200 CSII

MDI

Nav

igat

or

Use

(h

ou

rs/w

eek)

Results – Sensor Use

BL 5-8 9-13 22-261-4 14-17 18-21

# subjects with zero use:

0 0 0 0 1 4 2

0 0 1 0 5 5 3

6.0

7.0

8.0

9.0CSII

MDI

Hb

A1c

(%

)

Baseline Wk 7 Wk 13 Wk 26

Results – Glycemic Control

Results – Glycemic Control

140

160

180

200

220CSII

MDI

BL 5-8 9-13 22-261-4 14-17 18-21

Mea

n B

loo

d G

luco

se (

mg

/dL

)

30%

40%

50%

60%

70%

80%CSII

MDI

BL 5-8 9-13 22-26

Per

cen

tag

e se

nso

r G

luco

se V

alu

es

In T

arg

et R

ang

e (7

1-18

0 m

g/d

L)

Results – Glycemic Targets

1-4 14-17 18-21

0%

2%

4%

6%

8%

Results – Hypoglycemia (MDI)P

erce

nta

ge

sen

sor

Glu

cose

Val

ues

B

elo

w T

arg

et R

ang

e (<

70

mg

/dL

)

BL 5-8 9-13 22-261-4 14-17 18-21

CSII

MDI

80

100

120

140

160

CSII

MDI

BL 5-8 9-13 22-26

Results – Glycemic Variability

1-4 14-17 18-21

Mea

n A

mp

litu

de

of

Gly

cem

icE

xcu

rsio

n (

MA

GE

, m

g/d

L)

Capillary Blood Glucose Testing

Need a graph like others showing meter use (tests/day)

over course of study

CGM Satisfaction

13 Wk 26 Wk

CSII – Subject

– Parent

3.6 ??

3.9 ??Need values

MDI – Subject

– Parent

3.5 0.5

3.8 0.4

3.6 0.5

3.8 0.5

Scores are out of a 5 point Likert scale

Factors Predictive of Continued Use

can be like table from paper,

but need p-values

Conclusions

• Navigator was well-tolerated in pediatric subjects using either CSII or glargine-based basal-bolus MDI over 26 weeks

• Decrease in sensor use over time• Early improvements in A1c, percentage of glucose

levels in range, and glycemic variability• No baseline factors were predictive of successful

extended use• Short-term use, early drop in HbA1c, and higher

levels of CGM satisfaction predict successful extended use

• Barbara Davis Center– H. Peter Chase– Rosanna Fiallo-Scharer– Laurel Messer– Barbara Tallant

• University of Iowa– Eva Tsalikian– Michael Tansey– Linda Larson– Julie Coffey– Joanne Cabbage

• Nemours Children’s Clinic– Tim Wysocki– Nelly Mauras– Larry Fox– Keisha Bird– Kim Englert

• Stanford University– Bruce Buckingham– Darrell Wilson– Jennifer Block– Paula Clinton

• Yale University– William Tamborlane– Stuart Weinzimer– Brett Ives– Amy Steffen

• Jaeb Center for Health Research– Roy Beck– Katrina Ruedy– Craig Kollman– Dongyuan Xing– Cynthia Stockdale

The following slides

are just audience questions

Audience Question 1:(before presentation)

• On a scale of 1 (lowest) to 5 (highest), how would you rate the tolerability of continuous glucose sensors in the management of children with diabetes ?– 1. Completely intolerable– 2. Somewhat intolerable– 3. Neither tolerable nor intolerable– 4. Somewhat tolerable– 5. Very tolerable

Audience Question 2:(before presentation)

• On a scale of 1 (lowest) to 5 (highest), how would you rate the usefulness of continuous glucose sensors in the management of children with diabetes ?– 1. Completely useless– 2. Somewhat useless– 3. Neither useful nor useless– 4. Somewhat useful– 5. Very useful

Audience Question 3:(before presentation)

• On a scale of 1 (lowest) to 5 (highest), how likely would you be to recommend the use of continuous glucose sensors in the management of children with diabetes ?– 1. Very unlikely– 2. Somewhat unlikely– 3. Neither unlikely nor likely– 4. Somewhat likely– 5. Very likely

Audience Question 1:(after presentation)

• On a scale of 1 (lowest) to 5 (highest), how would you rate the tolerability of continuous glucose sensors in the management of children with diabetes ?– 1. Completely intolerable– 2. Somewhat intolerable– 3. Neither tolerable nor intolerable– 4. Somewhat tolerable– 5. Very tolerable

Audience Question 2:(after presentation)

• On a scale of 1 (lowest) to 5 (highest), how would you rate the usefulness of continuous glucose sensors in the management of children with diabetes ?– 1. Completely useless– 2. Somewhat useless– 3. Neither useful nor useless– 4. Somewhat useful– 5. Very useful

Audience Question 3:(after presentation)

• On a scale of 1 (lowest) to 5 (highest), how likely would you be to recommend the use of continuous glucose sensors in the management of children with diabetes ?– 1. Very unlikely– 2. Somewhat unlikely– 3. Neither unlikely nor likely– 4. Somewhat likely– 5. Very likely