Comparison of Lantus and NPH Insulin in the Dawn Phenomenon (DAWN)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2010 by Massachusetts General Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Sanofi
Information provided by:
Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00694122
First received: June 6, 2008
Last updated: July 28, 2010
Last verified: July 2010

June 6, 2008
July 28, 2010
June 2005
November 2010   (final data collection date for primary outcome measure)
Hourly blood glucose, cortisol, growth hormone, glucagon, and insulin levels [ Time Frame: Overnight testing from 20:00 to 08:00 ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00694122 on ClinicalTrials.gov Archive Site
Subject preference to insulin type [ Time Frame: During each intervention period (3-4 weeks) ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Comparison of Lantus and NPH Insulin in the Dawn Phenomenon
Comparison of Lantus and NPH Insulin in the Dawn Phenomenon
  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.

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.

Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Type 1 Diabetes
  • Dawn Phenomenon
Drug: alternate long acting insulin, either NPH or Lantus
NPH or Lantus, dose individualized for subject
Experimental: v3
Long acting insulin that subject currently uses
Intervention: Drug: alternate long acting insulin, either NPH or Lantus
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
18
November 2010
November 2010   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact: CHRISTINE STEVENS, RN 617-643-0915 CSTEVENS@PARTNERS.ORG
Contact: RICHARD POMPEI, RN 617-726-2141 RPOMPEI@PARTNERS.ORG
United States
 
NCT00694122
2005-P-002515/24
Yes
Dr. David Nathan MD, Massachuesetts General Hospital
Massachusetts General Hospital
Sanofi
Principal Investigator: David M Nathan, MD Massachusetts General Hospital
Massachusetts General Hospital
July 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP