Trial Outcomes & Findings for Effect of Metabolic Control at Onset of Diabetes on Progression of Type 1 Diabetes (NCT NCT00891995)

NCT ID: NCT00891995

Last Updated: 2016-12-30

Results Overview

In the primary analysis of the 12-month Mixed-Meal Tolerance Test (MMTT) results, the geometric mean (95% C.I.) of C-peptide average AUC (=AUC/time) was 0.43 (0.34, 0.52) pmol/ml in the intensive treatment group and 0.52 (0.32, 0.75) pmol/ml in the usual care group (P=0.49).

• Recruitment status: TERMINATED
• Study phase: PHASE2/PHASE3
• Target enrollment: 71 participants
• Primary outcome timeframe: At baseline, MMTT data were collected at 0 and 90 min; at 12 months, MMTT data were collected at 0 to 240 min post meal
• Results posted on: 2016-12-30

Participant Flow

Participant milestones

Measure	Intensive Treatment The Intensive Treatment group will participate in 4-6 days of inpatient closed loop therapy followed by use of an insulin pump and continuous glucose monitoring (CGM) in addition to standard monitoring with a home glucose meter for 2 years.	Standard Treatment The Standard Care group will receive standard diabetes management using a home glucose meter for blood sugar monitoring for 2 years.
Overall Study STARTED	50	21
Overall Study COMPLETED	50	21
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effect of Metabolic Control at Onset of Diabetes on Progression of Type 1 Diabetes

Baseline characteristics by cohort

Measure	Intensive Treatment n=48 Participants The Intensive Treatment group will participate in 4-6 days of inpatient closed loop therapy followed by use of an insulin pump and CGM in addition to standard monitoring with a home glucose meter for 2 years.	Standard Treatment n=20 Participants The Standard Care group will receive standard diabetes management using a home glucose meter for blood sugar monitoring for 2 years.	Total n=68 Participants Total of all reporting groups
Age, Categorical <=18 years	46 Participants n=93 Participants	19 Participants n=4 Participants	65 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Continuous	12.7 years STANDARD_DEVIATION 4.7 • n=93 Participants	14.7 years STANDARD_DEVIATION 7.6 • n=4 Participants	13.3 years STANDARD_DEVIATION 5.7 • n=27 Participants
Gender Female	17 Participants n=93 Participants	7 Participants n=4 Participants	24 Participants n=27 Participants
Gender Male	31 Participants n=93 Participants	13 Participants n=4 Participants	44 Participants n=27 Participants
Race/Ethnicity, Customized White	42 participants n=93 Participants	18 participants n=4 Participants	60 participants n=27 Participants
Race/Ethnicity, Customized Black	1 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants
Race/Ethnicity, Customized Hispanic or Latino	2 participants n=93 Participants	1 participants n=4 Participants	3 participants n=27 Participants
Race/Ethnicity, Customized More than one race	1 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants
Race/Ethnicity, Customized Unknown	2 participants n=93 Participants	1 participants n=4 Participants	3 participants n=27 Participants

PRIMARY outcome

Timeframe: At baseline, MMTT data were collected at 0 and 90 min; at 12 months, MMTT data were collected at 0 to 240 min post meal

Population: Among the 68 participants who completed 1 year visit and with positive autoantibody, 1 participant in the intensive treatment group did not complete MMTT test, thus was excluded from all C-peptide analyses.

In the primary analysis of the 12-month Mixed-Meal Tolerance Test (MMTT) results, the geometric mean (95% C.I.) of C-peptide average AUC (=AUC/time) was 0.43 (0.34, 0.52) pmol/ml in the intensive treatment group and 0.52 (0.32, 0.75) pmol/ml in the usual care group (P=0.49).

Outcome measures

Measure	Standard Treatment n=20 Participants The Standard Care group will receive standard diabetes management using a home glucose meter for blood sugar monitoring for 2 years.	Intensive Treatment n=47 Participants The Intensive Treatment group will participate in 4-6 days of inpatient closed loop therapy followed by use of an insulin pump and CGM in addition to standard monitoring with a home glucose meter for 2 years.
C-peptide Average Area Under the Curve (AUC) in Response to a Mixed Meal at 1 Year Following Enrollment.	0.52 pmol/ml Interval 0.32 to 0.75	0.43 pmol/ml Interval 0.34 to 0.52

SECONDARY outcome

Timeframe: 0 to 240 min post meal at 1 year MMTT

Population: Among the 68 participants who completed 1 year visit and with positive autoantibody, 1 participant in the intensive treatment group did not complete MMTT test, thus was excluded from all C-peptide analyses.

Outcome measures

Measure	Standard Treatment n=20 Participants The Standard Care group will receive standard diabetes management using a home glucose meter for blood sugar monitoring for 2 years.	Intensive Treatment n=47 Participants The Intensive Treatment group will participate in 4-6 days of inpatient closed loop therapy followed by use of an insulin pump and CGM in addition to standard monitoring with a home glucose meter for 2 years.
Peak C-peptide in Response to a Mixed Meal at 1 Year Following Enrollment	0.65 pmol/ml Interval 0.4 to 0.95	0.53 pmol/ml Interval 0.42 to 0.65

SECONDARY outcome

Timeframe: 0 to 240 min post meal at 1 year MMTT

Population: Among the 68 participants who completed 1 year visit and with positive autoantibody, 1 participant in the intensive treatment group did not complete MMTT test, thus was excluded from all C-peptide analyses.

Outcome measure in the table is the incidence of 2 hour peak C-peptide>=0.2 pmol/ml. Since the formal clinical trial stopped at 12 months due to lack of efficiency (later follow-up were used to collect data for secondary analyses by pooling the two groups), only the outcome at 12 months are reported.

Outcome measures

Measure	Standard Treatment n=20 Participants The Standard Care group will receive standard diabetes management using a home glucose meter for blood sugar monitoring for 2 years.	Intensive Treatment n=47 Participants The Intensive Treatment group will participate in 4-6 days of inpatient closed loop therapy followed by use of an insulin pump and CGM in addition to standard monitoring with a home glucose meter for 2 years.
Incidence of the Loss of the 2 Hour Peak C-peptide < 0.2 Pmol/ml on a Semi-annual MMTT	16 participants	37 participants

SECONDARY outcome

Timeframe: 1 year

Outcome measures

Measure	Standard Treatment n=20 Participants The Standard Care group will receive standard diabetes management using a home glucose meter for blood sugar monitoring for 2 years.	Intensive Treatment n=48 Participants The Intensive Treatment group will participate in 4-6 days of inpatient closed loop therapy followed by use of an insulin pump and CGM in addition to standard monitoring with a home glucose meter for 2 years.
HbA1c	7.3 percent Standard Deviation 1.1	7.4 percent Standard Deviation 1.2

SECONDARY outcome

Timeframe: 1 year

Outcome measures

Measure	Standard Treatment n=20 Participants The Standard Care group will receive standard diabetes management using a home glucose meter for blood sugar monitoring for 2 years.	Intensive Treatment n=48 Participants The Intensive Treatment group will participate in 4-6 days of inpatient closed loop therapy followed by use of an insulin pump and CGM in addition to standard monitoring with a home glucose meter for 2 years.
Adverse Events (Severe Hypoglycemia)	0 participants	1 participants

SECONDARY outcome

Timeframe: 1 year

Population: Participants who used CGM (either blinded or unblinded CGM) for at least 24 hours at 12 months.

Outcome measures

Measure	Standard Treatment n=15 Participants The Standard Care group will receive standard diabetes management using a home glucose meter for blood sugar monitoring for 2 years.	Intensive Treatment n=31 Participants The Intensive Treatment group will participate in 4-6 days of inpatient closed loop therapy followed by use of an insulin pump and CGM in addition to standard monitoring with a home glucose meter for 2 years.
CGM Mean Glucose	152 mg/dL Interval 145.0 to 171.0	150 mg/dL Interval 117.0 to 186.0

SECONDARY outcome

Timeframe: 1 year

Population: Participants who used CGM (either blinded or unblinded CGM) for at least 24 hours at 12 months.

Include a series of glucose indices created from CGM measured glucose data, such as % time with glucose values <=70 mg/dl, % time with glucose values within target range of 71-180 mg/dl, % time with glucose values >180 mg/dl, and glucose variability as measured by coefficient of variation. These indices were calculated by giving equal weight to each of the 24 h of the day. At least 24 h of CGM data were required for calculating these indices.

Outcome measures

Measure	Standard Treatment n=15 Participants The Standard Care group will receive standard diabetes management using a home glucose meter for blood sugar monitoring for 2 years.	Intensive Treatment n=31 Participants The Intensive Treatment group will participate in 4-6 days of inpatient closed loop therapy followed by use of an insulin pump and CGM in addition to standard monitoring with a home glucose meter for 2 years.
CGM Measured Glucose Outcomes %Glucose 71-180 mg/dL	70 percent Interval 57.0 to 79.0	69 percent Interval 47.0 to 83.0
CGM Measured Glucose Outcomes %Glucose <=70 mg/dL	0.7 percent Interval 0.0 to 5.0	2.5 percent Interval 0.4 to 7.7
CGM Measured Glucose Outcomes %Glucose >180 mg/dL	22 percent Interval 18.0 to 41.0	27 percent Interval 8.0 to 49.0
CGM Measured Glucose Outcomes %Coefficient of variation	35 percent Interval 28.0 to 38.0	35 percent Interval 29.0 to 39.0

SECONDARY outcome

Timeframe: 1 year

Outcome measures

Measure	Standard Treatment n=20 Participants The Standard Care group will receive standard diabetes management using a home glucose meter for blood sugar monitoring for 2 years.	Intensive Treatment n=48 Participants The Intensive Treatment group will participate in 4-6 days of inpatient closed loop therapy followed by use of an insulin pump and CGM in addition to standard monitoring with a home glucose meter for 2 years.
Daily Insulin Dose	0.6 u/day/kg Standard Deviation 0.3	0.6 u/day/kg Standard Deviation 0.2

SECONDARY outcome

Timeframe: 1 year

Outcome measures

Measure	Standard Treatment n=19 Participants The Standard Care group will receive standard diabetes management using a home glucose meter for blood sugar monitoring for 2 years.	Intensive Treatment n=46 Participants The Intensive Treatment group will participate in 4-6 days of inpatient closed loop therapy followed by use of an insulin pump and CGM in addition to standard monitoring with a home glucose meter for 2 years.
BMI Percentile	62 percent Interval 40.0 to 72.0	58 percent Interval 39.0 to 81.0

Adverse Events

Intensive Treatment

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Standard Treatment

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Intensive Treatment n=48 participants at risk The Intensive Treatment group will participate in 4-6 days of inpatient closed loop therapy followed by use of an insulin pump and CGM in addition to standard monitoring with a home glucose meter for 2 years.	Standard Treatment n=20 participants at risk The Standard Care group will receive standard diabetes management using a home glucose meter for blood sugar monitoring for 2 years.
Gastrointestinal disorders gastroenteritis	0.00% 0/48 • 1 year	5.0% 1/20 • Number of events 1 • 1 year
General disorders Anaphylactic reaction	2.1% 1/48 • Number of events 1 • 1 year	0.00% 0/20 • 1 year
Psychiatric disorders Suicidal ideation	2.1% 1/48 • Number of events 1 • 1 year	0.00% 0/20 • 1 year

Other adverse events

Measure	Intensive Treatment n=48 participants at risk The Intensive Treatment group will participate in 4-6 days of inpatient closed loop therapy followed by use of an insulin pump and CGM in addition to standard monitoring with a home glucose meter for 2 years.	Standard Treatment n=20 participants at risk The Standard Care group will receive standard diabetes management using a home glucose meter for blood sugar monitoring for 2 years.
Endocrine disorders severe hypoglycemia	2.1% 1/48 • Number of events 2 • 1 year	0.00% 0/20 • 1 year
Vascular disorders venous thrombosis	4.2% 2/48 • Number of events 2 • 1 year	0.00% 0/20 • 1 year
General disorders faint	2.1% 1/48 • Number of events 1 • 1 year	0.00% 0/20 • 1 year
Skin and subcutaneous tissue disorders skin infection	2.1% 1/48 • Number of events 1 • 1 year	0.00% 0/20 • 1 year
Psychiatric disorders depression and anxiety	0.00% 0/48 • 1 year	10.0% 2/20 • Number of events 2 • 1 year
Skin and subcutaneous tissue disorders Needle stick/puncture	2.1% 1/48 • Number of events 1 • 1 year	0.00% 0/20 • 1 year

Additional Information

Katrina Ruedy

Jaeb Center for Health Research

Phone: 8139758690

Email: kruedy@jaeb.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place