HUCKEPACK2: Comparison of Premixed Insulins Aspart 30, Aspart 70 and Aspart on Postprandial Lipids

• Sponsor: Medical University of Graz (Other)
• Overall Status: Completed
• CT.gov ID: NCT01293396
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arms: 3
• Duration (Months): 9
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief Summary

The aim of the study is to investigate meal-related treatment with either premixed Insulin Aspart 30, Aspart 70 and Aspart with regard to postprandial glucose, triglyceride and free fatty acids excursions after a standard breakfast and lunch.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Drug: Insulin Aspart; Drug: Insulin Aspart 30; Drug: Insulin Aspart 70	Phase 4

Detailed Description

Whereas the effects of each of the established types of insulin (remixed Insulin Aspart 30, Aspart 70 and Aspart) have been shown before, their specific glucose and lipid lowering capacities have so far not been investigated in a simulated physiological situation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Comparison of the Impact of Biphasic Insulin Aspart 30 (BiAsp 30), Biphasic Insulin Aspart 70 (BiAsp 70) and Insulin Aspart on Postprandial Glucose and Lipid Metabolism During Two Consecutive Meals in Type 2 Diabetics.
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Feb 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Biphasic Insulin Aspart 30 35% of their usual total daily insulin dose before the standardized breakfast and 25% prior to lunch	Drug: Insulin Aspart 30; Patients received biphasic insulin aspart 30 before breakfast and before lunch.; Other Names: Novomix 30
Active Comparator: Biphasic Insulin Aspart 70 35% of their usual total daily insulin dose before the standardized breakfast and 25% prior to lunch	Drug: Insulin Aspart 70; Patients received biphasic insulin aspart 70 before breakfast and before lunch.; Other Names: Novomix 70
Active Comparator: Insulin Aspart 35% of their usual total daily insulin dose before the standardized breakfast and 25% prior to lunch	Drug: Insulin Aspart; Patients received insulin aspart before breakfast and before lunch.; Other Names: Novorapid

Outcome Measures

Primary Outcome Measures

1. Area Over Basal for Postprandial Glucose From 0 to 600min [0,30,60,90,120,180,240,270,300,330,360,420,480,540,600 minutes post-dose (daily study start)]

   Area over basal for postprandial glucose from 0 (Fasting glucose, measured at daily study start) to 600 min (after breakfast) Area over basal is calculated according to the trapezoidal rule.

2. Area Over Basal for Postprandial Triglycerides [0,30,60,90,120,180,240,270,300,330,360,420,480,540,600 minutes post-dose (daily study start)]

   Area over basal for postprandial triglycerides from 0 (Fasting triglycerides, measured at daily study start) to 600 min (after breakfast) Area over basal is calculated according to the trapezoidal rule.

Secondary Outcome Measures

1. Maximum Glucose Increase [0,30,60,90,120,180,240,270,300,330,360,420,480,540,600 minutes post-dose (daily study start)]

   Maximum glucose increase from baseline to 600min after baseline

2. Maximum Triglyceride Increase [0,30,60,90,120,180,240,270,300,330,360,420,480,540,600 minutes post-dose (daily study start)]

   Maximum trigylceride increase from Baseline to 600min after Baseline

3. Area Over Basal for Postprandial Insulin [0,30,60,90,120,180,240,270,300,330,360,420,480,540,600 minutes post-dose (daily study start)]

   Area over basal for postprandial insulin from 0 (Fasting insulin, measured at daily study start) to 600 min (after breakfast) Area over basal is calculated according to the trapezoidal rule.

4. Area Over Basal for Postprandial C-peptide [0,30,60,90,120,180,240,270,300,330,360,420,480,540,600 minutes post-dose (daily study start)]

   Area over basal for postprandial c-peptide from 0 (Fasting c-peptide, measured at daily study start) to 600 min (after breakfast) Area over basal is calculated according to the trapezoidal rule.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type-II Diabetes

• BMI > 27 kg/m2

• age 35 to 75 years

• HbA1c < 8.5%

• informed consent

• treatment with pre-mixed insulin

• stabile dose of insulin for at least 4 weeks

Exclusion Criteria:

• Type-I Diabetes mellitus

• HbA1c > 8.5 %

• Serum Creatinine > 1.7 mg/dl

• Alaninaminotranferase or Aspartataminotransferase > 3x Upper Limit of Normal

• treatment with sulfonylurea or gliptins

• treatment with glitazones

• manifest clinical infections

• treatment with glucocorticoids or antipsychotic drugs

• psychiatric diseases

• alcohol abuse

• myocardial infarction or stroke within the previous 3 months

• surgery within the previous 3 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University of Graz, Department for Internal Medicine	Graz		Austria	8036

Sponsors and Collaborators

• Medical University of Graz

Investigators

• Principal Investigator: Harald Sourij, MD, Medical University of Graz, 8036 Graz, Austria

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Medical University of Graz
• ClinicalTrials.gov Identifier: NCT01293396
• Other Study ID Numbers: ENM-DA-008; 2008-008486-35
• First Posted: Feb 10, 2011
• Last Update Posted: Jun 30, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by Medical University of Graz: insulin aspart 30; insulin aspart 70; insulin aspart; postprandial glucose and lipid metabolism; consecutive mixed meals
• Additional relevant MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination; Insulin aspart, insulin aspart protamine drug combination 30:70

Study Results

Participant Flow

Recruitment Details	50 patients were screened and in total 20 randomizations were performed. After randomization 20 randomized subjects finished all three study visits.
Pre-assignment Detail	All subjects received all of the three insulins within various sequences in a randomized order. Randomisation lists for the insulin sequence were provided by a researcher otherwise not involved in the clinical trial performance.

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	Participants were randomized to each intervention and re-randomized to the remaining interventions after each washout period.	Participants were randomized to each intervention and re-randomized to the remaining interventions after each washout period	Participants were randomized to each intervention and re-randomized to the remaining interventions after each washout period.
Period Title: First Intervention
STARTED	6	7	7
COMPLETED	6	7	7
NOT COMPLETED	0	0	0
Period Title: First Intervention
STARTED	6	7	7
COMPLETED	6	7	7
NOT COMPLETED	0	0	0
Period Title: First Intervention
STARTED	5	5	10
COMPLETED	5	5	10
NOT COMPLETED	0	0	0
Period Title: First Intervention
STARTED	5	5	10
COMPLETED	5	5	10
NOT COMPLETED	0	0	0
Period Title: First Intervention
STARTED	9	8	3
COMPLETED	9	8	3
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description	20 patients with type 2 diabetes receive insulin aspart, premixed biphasic insulin 30 and premixed biphasic insulin aspart 70 in randomized order.
Overall Participants	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65 (6)
Sex: Female, Male (Count of Participants)
Female	6 30%
Male	14 70%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	20 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Area Over Basal for Postprandial Glucose From 0 to 600min
Description	Area over basal for postprandial glucose from 0 (Fasting glucose, measured at daily study start) to 600 min (after breakfast) Area over basal is calculated according to the trapezoidal rule.
Time Frame	0,30,60,90,120,180,240,270,300,330,360,420,480,540,600 minutes post-dose (daily study start)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Biphasic Insulin Aspart 30	Biphasic Insulin Aspart 70	Insulin Aspart
Arm/Group Description	Insulin Aspart 30: Patients received biphasic insulin aspart 30 before breakfast and before lunch.	Insulin Aspart 70: Patients received biphasic insulin aspart 70 before breakfast and before lunch.	Insulin Aspart: Patients received insulin aspart before breakfast and before lunch.
Measure Participants	20	20	20
Mean (Standard Deviation) [mg*/min/dL]	591 (681)	220 (617)	197 (550)

2. Primary Outcome

Title	Area Over Basal for Postprandial Triglycerides
Description	Area over basal for postprandial triglycerides from 0 (Fasting triglycerides, measured at daily study start) to 600 min (after breakfast) Area over basal is calculated according to the trapezoidal rule.
Time Frame	0,30,60,90,120,180,240,270,300,330,360,420,480,540,600 minutes post-dose (daily study start)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Biphasic Insulin Aspart 30	Biphasic Insulin Aspart 70	Insulin Aspart
Arm/Group Description	Insulin Aspart 30: Patients received biphasic insulin aspart 30 before breakfast and before lunch.	Insulin Aspart 70: Patients received biphasic insulin aspart 70 before breakfast and before lunch.	Insulin Aspart: Patients received insulin aspart before breakfast and before lunch.
Measure Participants	20	20	20
Mean (Standard Deviation) [mg*min/dL]	484 (342)	358 (544)	412 (831)

3. Secondary Outcome

Title	Maximum Glucose Increase
Description	Maximum glucose increase from baseline to 600min after baseline
Time Frame	0,30,60,90,120,180,240,270,300,330,360,420,480,540,600 minutes post-dose (daily study start)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Biphasic Insulin Aspart 30	Biphasic Insulin Aspart 70	Insulin Aspart
Arm/Group Description	Insulin Aspart 30: Patients received biphasic insulin aspart 30 before breakfast and before lunch.	Insulin Aspart 70: Patients received biphasic insulin aspart 70 before breakfast and before lunch.	Insulin Aspart: Patients received insulin aspart before breakfast and before lunch.
Measure Participants	20	20	20
Mean (Standard Deviation) [mg/dL]	89.25 (57.85)	55.95 (42.44)	60.25 (40.45)

4. Secondary Outcome

Title	Maximum Triglyceride Increase
Description	Maximum trigylceride increase from Baseline to 600min after Baseline
Time Frame	0,30,60,90,120,180,240,270,300,330,360,420,480,540,600 minutes post-dose (daily study start)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Biphasic Insulin Aspart 30	Biphasic Insulin Aspart 70	Insulin Aspart
Arm/Group Description	Insulin Aspart 30: Patients received biphasic insulin aspart 30 before breakfast and before lunch.	Insulin Aspart 70: Patients received biphasic insulin aspart 70 before breakfast and before lunch.	Insulin Aspart: Patients received insulin aspart before breakfast and before lunch.
Measure Participants	20	20	20
Mean (Standard Deviation) [mg/dL]	484 (342)	358 (544)	412 (831)

5. Secondary Outcome

Title	Area Over Basal for Postprandial Insulin
Description	Area over basal for postprandial insulin from 0 (Fasting insulin, measured at daily study start) to 600 min (after breakfast) Area over basal is calculated according to the trapezoidal rule.
Time Frame	0,30,60,90,120,180,240,270,300,330,360,420,480,540,600 minutes post-dose (daily study start)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Biphasic Insulin Aspart 30	Biphasic Insulin Aspart 70	Insulin Aspart
Arm/Group Description	Insulin Aspart 30: Patients received biphasic insulin aspart 30 before breakfast and before lunch.	Insulin Aspart 70: Patients received biphasic insulin aspart 70 before breakfast and before lunch.	Insulin Aspart: Patients received insulin aspart before breakfast and before lunch.
Measure Participants	20	20	20
Mean (Standard Deviation) [µU*min/L]	211.2 (149.7)	141.2 (155.3)	128.6 (106.7)

6. Secondary Outcome

Title	Area Over Basal for Postprandial C-peptide
Description	Area over basal for postprandial c-peptide from 0 (Fasting c-peptide, measured at daily study start) to 600 min (after breakfast) Area over basal is calculated according to the trapezoidal rule.
Time Frame	0,30,60,90,120,180,240,270,300,330,360,420,480,540,600 minutes post-dose (daily study start)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Biphasic Insulin Aspart 30	Biphasic Insulin Aspart 70	Insulin Aspart
Arm/Group Description	Insulin Aspart 30: Patients received biphasic insulin aspart 30 before breakfast and before lunch.	Insulin Aspart 70: Patients received biphasic insulin aspart 70 before breakfast and before lunch.	Insulin Aspart: Patients received insulin aspart before breakfast and before lunch.
Measure Participants	20	20	20
Mean (Standard Deviation) [mg*min/mL]	21.6 (14.1)	12.8 (11.5)	13.4 (11.8)

Adverse Events

Arm/Group Title	Biphasic Insulin Aspart 30		Biphasic Insulin Aspart 70		Insulin Aspart
Arm/Group Description	Insulin Aspart 30: Patients received biphasic insulin aspart 30 before breakfast and before lunch.		Insulin Aspart 70: Patients received biphasic insulin aspart 70 before breakfast and before lunch.		Insulin Aspart: Patients received insulin aspart before breakfast and before lunch.
All Cause Mortality
	Biphasic Insulin Aspart 30		Biphasic Insulin Aspart 70		Insulin Aspart
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)		0/20 (0%)
Serious Adverse Events
	Biphasic Insulin Aspart 30		Biphasic Insulin Aspart 70		Insulin Aspart
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Biphasic Insulin Aspart 30		Biphasic Insulin Aspart 70		Insulin Aspart
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/20 (5%)		2/20 (10%)		2/20 (10%)
Endocrine disorders
Mild Hypoglycaemic Event	1/20 (5%)	2	2/20 (10%)	4	2/20 (10%)	2
Moderate Hypoglycaemic Event	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.