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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00191464




Registration number
NCT00191464
Ethics application status
Date submitted
12/09/2005
Date registered
19/09/2005
Date last updated
13/10/2010

Titles & IDs
Public title
Long-Term Effects of Insulin Plus Metformin Regimens on the Overall and Postprandial Glycemic Control of Patients With Type 2 Diabetes
Scientific title
Long-Term Effects of Insulin Plus Metformin Regimens on the Overall and Postprandial Glycemic Control of Patients With Type 2 Diabetes: A Comparison of Premeal Insulin Lispro Mixtures to Once-Daily Insulin Glargine
Secondary ID [1] 0 0
F3Z-MC-IOOI
Secondary ID [2] 0 0
6146
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 2 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
HbA1C
Timepoint [1] 0 0
Secondary outcome [1] 0 0
General inflammation (hsCRP)
Timepoint [1] 0 0
Secondary outcome [2] 0 0
High-density lipoprotein cholesterol
Timepoint [2] 0 0
Secondary outcome [3] 0 0
Total cholesterol
Timepoint [3] 0 0
Secondary outcome [4] 0 0
Triglycerides
Timepoint [4] 0 0
Secondary outcome [5] 0 0
Estimates of low-density lipoprotein cholesterol
Timepoint [5] 0 0
Secondary outcome [6] 0 0
Nuclear magnetic resonance [NMR] analysis of lipids
Timepoint [6] 0 0
Secondary outcome [7] 0 0
Oxidized LDL
Timepoint [7] 0 0
Secondary outcome [8] 0 0
Lipoproteins and apoproteins
Timepoint [8] 0 0
Secondary outcome [9] 0 0
Fibrinogen
Timepoint [9] 0 0
Secondary outcome [10] 0 0
Blood glucose levels (based on self-monitoring)
Timepoint [10] 0 0
Secondary outcome [11] 0 0
Insulin dose
Timepoint [11] 0 0
Secondary outcome [12] 0 0
Weight
Timepoint [12] 0 0
Secondary outcome [13] 0 0
Frequency and incidence of hypoglycemia
Timepoint [13] 0 0
Secondary outcome [14] 0 0
Safety
Timepoint [14] 0 0
Secondary outcome [15] 0 0
General well-being
Timepoint [15] 0 0
Secondary outcome [16] 0 0
Pilot two questionnaires for microvascular complications
Timepoint [16] 0 0
Secondary outcome [17] 0 0
Coagulopathy factors [substudy]
Timepoint [17] 0 0
Secondary outcome [18] 0 0
Surrogate measure of vascular reactivity [substudy]
Timepoint [18] 0 0
Secondary outcome [19] 0 0
Inflammatory markers [substudy]
Timepoint [19] 0 0
Secondary outcome [20] 0 0
Production of advanced glycation end-products [substudy]
Timepoint [20] 0 0
Secondary outcome [21] 0 0
Generation of oxidative species [substudy]
Timepoint [21] 0 0
Secondary outcome [22] 0 0
Lipids in various fractions [substudy]
Timepoint [22] 0 0
Secondary outcome [23] 0 0
Retinyl ester measurements in various fractions [substudy]
Timepoint [23] 0 0
Secondary outcome [24] 0 0
Composition of triglyceride-rich lipoproteins [substudy]
Timepoint [24] 0 0
Secondary outcome [25] 0 0
Compartmental modeling of postprandial lipemia [substudy]
Timepoint [25] 0 0
Secondary outcome [26] 0 0
Apolipoproteins [substudy]
Timepoint [26] 0 0

Eligibility
Key inclusion criteria
* Have type 2 diabetes (World Health Organization [WHO] classification
* Have used one or more of the following oral anti-hyperglycemic medications-metformin or second-generation sulfonylurea (for example, glibenclamide, glyburide, glipizide, gliclazide, glimepiride) alone or in combination with one or two insulin injections per day for at least 3 months immediately prior to entering the study. Patients using more than 2 insulin injections per day or subcutaneous insulin infusion prior to the study will not be eligible to participate.
* Have a hemoglobin A1c between 6.5% and 11%, inclusive, according to the central laboratory at Visit 1.
* Have clinically acceptable LDL-C, in the investigator's opinion, at Visit 1.
* As determined by the investigator, are capable and willing to learn how to use the insulin injection pens; comply with their prescribed diet, exercise, and medication regimen; perform self-monitoring of blood glucose; and use the patient diary as required for this protocol.
Minimum age
35 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Have hypersensitivity to metformin or a known allergy to metformin hydrochloride, insulin lispro MM, insulin lispro LM, or insulin glargine, or excipients contained in these products.
* Have known metabolic or lactic acidosis.
* Have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine greater than or equal to 135 micromol/L (1.5 mg/dL) for males and greater than or equal to 110 micromol/L (1.2 mg/dL) for females.
* Have cardiac disease with functional status that is Class III or IV
* Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine transaminase (ALT) greater than three times the upper limit of the reference range as defined by the central laboratory.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2003
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - St Leonards
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New Hampshire
Country [2] 0 0
Greece
State/province [2] 0 0
Thessaloniki
Country [3] 0 0
India
State/province [3] 0 0
Maharstra
Country [4] 0 0
Netherlands
State/province [4] 0 0
Den Helder
Country [5] 0 0
Poland
State/province [5] 0 0
Olesnica
Country [6] 0 0
Puerto Rico
State/province [6] 0 0
Ponce

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study is to show that a prandial insulin regimen, consisting of premeal insulin lispro "mid mixture" (or a combined regimen of insulin lispro "mid mixture" and insulin lispro "low mixture") plus metformin will result in significantly better overall glycemic control (lower HbA1c) at endpoint than once-daily insulin glargine plus metformin. Insulin lispro "mid mixture" consists of 50% insulin lispro and 50% NPL. Insulin lispro "low mixture" consists of 25% insulin lispro and 75% NPL.

In a substudy of approximately 60 patients, additional data will be collected on markers associated with risk of atherosclerosis or cardiovascular disease in the context of a controlled, outpatient, high-fat test meal.
Trial website
https://clinicaltrials.gov/study/NCT00191464
Trial related presentations / publications
Robbins DC, Beisswenger PJ, Ceriello A, Goldberg RB, Moses RG, Pagkalos EM, Milicevic Z, Jones CA, Sarwat S, Tan MH. Mealtime 50/50 basal + prandial insulin analogue mixture with a basal insulin analogue, both plus metformin, in the achievement of target HbA1c and pre- and postprandial blood glucose levels in patients with type 2 diabetes: a multinational, 24-week, randomized, open-label, parallel-group comparison. Clin Ther. 2007 Nov;29(11):2349-64. doi: 10.1016/j.clinthera.2007.11.016.
Hirsch IB, Yuan H, Campaigne BN, Tan MH. Impact of prandial plus basal vs basal insulin on glycemic variability in type 2 diabetic patients. Endocr Pract. 2009 May-Jun;15(4):343-8. doi: 10.4158/EP08308.ORR.
Chan JY, Leyk M, Frier BM, Tan MH. Relationship between HbA1c and hypoglycaemia in patients with type 2 diabetes treated with different insulin regimens in combination with metformin. Diabetes Metab Res Rev. 2009 Mar;25(3):224-31. doi: 10.1002/dmrr.929.
Shrom D, Sarwat S, Ilag L, Bloomgarden ZT. Does A1c consistently reflect mean plasma glucose? J Diabetes. 2010 Jun;2(2):92-6. doi: 10.1111/j.1753-0407.2010.00066.x. Epub 2010 Jan 22.
Sarwat S, Ilag LL, Carey MA, Shrom DS, Heine RJ. The relationship between self-monitored blood glucose values and glycated haemoglobin in insulin-treated patients with Type 2 diabetes. Diabet Med. 2010 May;27(5):589-92. doi: 10.1111/j.1464-5491.2010.02955.x.
Beisswenger PJ, Brown WV, Ceriello A, Le NA, Goldberg RB, Cooke JP, Robbins DC, Sarwat S, Yuan H, Jones CA, Tan MH; IOOI Study Investigators. Meal-induced increases in C-reactive protein, interleukin-6 and tumour necrosis factor alpha are attenuated by prandial + basal insulin in patients with Type 2 diabetes. Diabet Med. 2011 Sep;28(9):1088-95. doi: 10.1111/j.1464-5491.2011.03324.x.
Public notes

Contacts
Principal investigator
Name 0 0
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00191464