Comparison of Lantus and Neutral Protamine Hagedorn (NPH) Insulin in the Dawn Phenomenon

NCT ID: NCT00694122

Last Updated: 2014-10-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-06-30
• Study Completion Date: 2010-11-30

Brief Summary

1. To investigate the effect of insulin glargine (Lantus™) vs NPH insulin regarding glycemic control during the early AM (dawn phenomenon) in individuals with type 1 diabetes.

2. To measure hormones implicated in the pathogenesis of the dawn phenomenon in individuals with type 1 diabetes.

Detailed Description

Title: COMPARISON of LANTUS and NPH INSULIN IN THE DAWN PHENOMENON

I. Background and Significance

Diabetes mellitus affects greater than 6% of the population, with type 2 more prevalent than type 1. For individuals with type 1 diabetes, the challenge has been to replicate insulin secretion of the healthy pancreas to maintain blood glucose as close to the non-diabetic range as possible. Insulin regimes using insulins with varied activity profiles (multiple daily injections or MDI) and continuous subcutaneous insulin infusion (CSII) have been somewhat successful in "mimicking" normal pancreatic function (1, 2). For individuals with type 1 diabetes, the benefits of near-normal, long-term glycemic control in delaying the development and slowing the progression of long-term complications was demonstrated in the Diabetes Control and Complications Trial (3). Intensive insulin therapy to achieve near-normal glycemic control has been limited by a three-fold increase in episodes of hypoglycemia (3, 4). Insulin analogs that provide more stable physiologic insulin levels have led to the development of newer MDI regimes (5). Glargine (Lantus) is a long-acting recombinant human insulin analog demonstrated to provide a continuous, smooth supply of insulin with no pronounced peak over a 24-hour period (6).

An increase in blood glucose in type 1 and type 2 diabetics, and an increase in insulin secretion to maintain normoglycemia in non-diabetics, was documented in several studies in the 1980s (15-17). This physiological requirement for more insulin delivery (or secretion) in the early (4:00-6:00 AM) hours was termed the "dawn phenomenon". The mechanism for the dawn phenomenon was thought to be the overnight increase in growth hormone section, rather than diurnal glucocorticoids (16, 18, 19). Most intensive treatment regimens of the 1980-90's, with MDI or CSII, were designed to provide more insulin in the 4:00-7:00 AM period to cope with the dawn phenomenon which cannot be be achieved with glargine (20-21). Continuous monitoring of blood glucose has revealed that individuals treated with CSII had significantly better glycemic control than glargine treated individuals (22). Whether the dawn phenomenon, with increased area under the curve blood glucose levels during the dawn period is limiting the effectiveness of regimens with glargine is of crucial importance.

Conditions

Type 1 Diabetes; Dawn Phenomenon

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Glargine (Lantus) insulin

Long acting insulin, glargine, that subject currently used as an outpatient. SC injections. Dose given at 22:00 is based on past week blood glucose data during evening overnight hours and AM glucose. 20.2 +/- 11.7 units glargine (mean +/- SD).

Glargine (Lantus): Sanolfi Aventis

Hourly blood glucose from 22:00 to 08:00 while receiving glargine (Lantus) insulin will be compared with the NPH insulin arm.

Group Type: ACTIVE_COMPARATOR

Lantus (glargine)

Intervention Type: DRUG

Described in Arm Description

NPH insulin

Long acting insulin, NPH, that participant was currently while an outpatient. SC injections. Dose (units) given at 22:00 is based on past week blood glucose during evening overnight period and AM glucose. 20.7 +/- 10.0 units NPH (mean +/- SD).

NPH: Eli Lilly

Hourly blood glucose from 22:00 to 08:00 while receiving glargine (Lantus) insulin will be compared with the glargine (Lantus) insulin arm.

Group Type: ACTIVE_COMPARATOR

Lantus (glargine)

Intervention Type: DRUG

Described in Arm Description

Interventions

Lantus (glargine)

Described in Arm Description

Intervention Type: DRUG

Other Intervention Names

Lantus (glargine): Sanolfi Aventis; NPH: Eli Lilly

Eligibility Criteria

Inclusion Criteria

• Written informed consent obtained prior to performing screening evaluations.
• Male or female, 18 yrs or older.
• Diagnosis of type 1 diabetes made 5 years prior to screening visit.
• A1C > 6.0% and 9.0% at screening visit.
• Body Mass Index (BMI) 35 kg/m2 at screening visit.
• Documented undetectable C-Peptide
• Ability to follow instructions for Continuous Glucose Monitoring System (CGMS).
• Multiple daily injection participants on at least 3 injections per day. May be treated with NPH or glargine.

Exclusion Criteria

• Pregnant or lactating females, or females planning to become pregnant during the study or not using an acceptable method of contraception. Females of childbearing potential must have a negative pregnancy test at Visit 3 and Visit 5. Females who become pregnant during the study will be discontinued.
• Type 2 diabetes.
• Two or more severe hypoglycemic episodes (requiring assistance) within six months of Screening.
• Drugs known to affect glycemia (eg. steroids, beta blockers) or conditions that are likely to require steroid therapy or cause metabolic instability in the next 6 months.
• History of allergy or intolerance to NPH or glargine.
• History of hypoglycemia unawareness i.e. no warning symptoms accompanying low (<50 mg/dl) blood glucose levels.
• Unable and/or unlikely to comprehend and/or follow the study protocol (including self blood glucose monitoring, CGMS).
• Currently using an insulin pump.
• Pituitary disorder (Acromegaly, Cushing's, Hypothyroidism etc.) or tumor.
• Two or more severe hypoglycemic episodes (requiring assistance) within six months of Screening.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

David M. Nathan, MD

Director, Diabetes Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David M Nathan, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusettes General Hospital/ Diabetes Research Center

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

2005-P-002515/24

Identifier Type: -

Identifier Source: org_study_id