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

This study has been completed.
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
David M. Nathan, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00694122
First received: June 6, 2008
Last updated: October 14, 2014
Last verified: October 2014
  Purpose
  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.

Condition Intervention Phase
Type 1 Diabetes
Dawn Phenomenon
Drug: Lantus (glargine)
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Comparison of Lantus and NPH Insulin in the Dawn Phenomenon

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Blood Glucose Area Under the Curve (AUC) [ Time Frame: Overnight ] [ Designated as safety issue: No ]
    Cumulative sum of repeatedly measured blood glucose values (mg/dl) beginning at 22:00, then hourly till 08:00. Participants were monitored during two overnight sampling periods. One overnight was while the participant was on neutral protamine Hagedorn (NPH) insulin as the long acting insulin; the other overnight was glargine (Lantus) insulin as the the long acting insulin.

  • Blood Glucose [ Time Frame: Overnight ] [ Designated as safety issue: No ]
    Average value of repeatedly measured absolute values beginning at 22:00, then hourly till 08:00. Participants were monitored during two overnight sampling periods. One overnight was while the participant was on NPH insulin as the long acting insulin; the other overnight was glargine(Lantus) insulin as the the long acting insulin.


Secondary Outcome Measures:
  • Insulin Dose [ Time Frame: Overnight ] [ Designated as safety issue: No ]
    NPH or glargine (Lantus) was given at 22:00 to provide blood glucose coverage during the overnight hours.

  • Cortisol [ Time Frame: Overnight ] [ Designated as safety issue: No ]
    Mean cortisol nmol/l during NPH or glargine (Lantus) overnight visit. Hourly cortisol was determined from 22:00 to 8:00.

  • Glucagon [ Time Frame: Overnight ] [ Designated as safety issue: No ]
    Mean glucagon mcg/l during NPH or glargine (Lantus) overnight visit. Hourly glucagon was determined from 22:00 to 8:00.

  • Growth Hormone [ Time Frame: Overnight ] [ Designated as safety issue: No ]
    Mean growth hormone ug/l during NPH or glargine (Lantus) overnight visit. Hourly growth hormone was determined from 22:00 to 8:00.


Enrollment: 27
Study Start Date: June 2005
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.

Drug: Lantus (glargine)
Described in Arm Description
Other Names:
  • Lantus (glargine): Sanolfi Aventis
  • NPH: Eli Lilly
Active Comparator: 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.

Drug: Lantus (glargine)
Described in Arm Description
Other Names:
  • Lantus (glargine): Sanolfi Aventis
  • NPH: Eli Lilly

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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&apos;s, Hypothyroidism etc.) or tumor.
  • Two or more severe hypoglycemic episodes (requiring assistance) within six months of Screening.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00694122

Locations
United States, Massachusetts
Massachusettes General Hospital/ Diabetes Research Center
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Sanofi
Investigators
Principal Investigator: David M Nathan, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: David M. Nathan, MD, Director, Diabetes Center, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00694122     History of Changes
Other Study ID Numbers: 2005-P-002515/24
Study First Received: June 6, 2008
Results First Received: November 4, 2013
Last Updated: October 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
glucose
cortisol
growth hormone
glucagon
insulin

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Autoimmune Diseases
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Glargine
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014