Type 1 DiabetesPhase 3DAWNNCT00694122
Comparison of Lantus and Neutral Protamine Hagedorn (NPH) Insulin in the Dawn Phenomenon
A Phase 3 study testing Lantus (glargine) in people with Type 1 Diabetes and Dawn Phenomenon, run by Massachusetts General Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type 1 Diabetes, Dawn Phenomenon
- What is being tested?
- Lantus (glargine)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2005to Nov 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusettes General Hospital/ Diabetes Research Center
Boston, Massachusetts, 02114
About this study
Official title: Comparison of Lantus and NPH Insulin in the Dawn Phenomenon
- 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.
- To measure hormones implicated in the pathogenesis of the dawn phenomenon in individuals with type 1 diabetes.
Read the detailed description
Title: COMPARISON of LANTUS and NPH INSULIN IN THE DAWN PHENOMENON
- 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
- Being tested
- Lantus (glargine)
- Keywords
- glucose, cortisol, growth hormone, glucagon, insulin
- Medical subject headings
- Diabetes Mellitus, Type 1, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lantus (glargine)Drug
Also called Lantus (glargine): Sanolfi Aventis, NPH: Eli Lilly
Described in Arm Description
| Study group | Role | What they receive |
|---|---|---|
| Glargine (Lantus) insulin | Active comparator | 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. Receives: Drug: Lantus (glargine) |
| NPH insulin | Active comparator | 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. Receives: Drug: Lantus (glargine) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood Glucose Area Under the Curve (AUC)
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.
Measured: Overnight
Blood Glucose
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.
Measured: Overnight
Secondary outcomes (4)
Insulin Dose
NPH or glargine (Lantus) was given at 22:00 to provide blood glucose coverage during the overnight hours.
Measured: Overnight
Cortisol
Mean cortisol nmol/l during NPH or glargine (Lantus) overnight visit. Hourly cortisol was determined from 22:00 to 8:00.
Measured: Overnight
Glucagon
Mean glucagon mcg/l during NPH or glargine (Lantus) overnight visit. Hourly glucagon was determined from 22:00 to 8:00.
Measured: Overnight
Growth Hormone
Mean growth hormone ug/l during NPH or glargine (Lantus) overnight visit. Hourly growth hormone was determined from 22:00 to 8:00.
Measured: Overnight
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2008 (estimated)
- Study startJun 2005
- Primary completionNov 2010
- Study completionNov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi
- Responsible party
- Principal investigator, David M. Nathan, MD, Massachusetts General Hospital
- Investigators
- David M Nathan, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00694122
- Sponsor's protocol ID
- 2005-P-002515/24
- Acronym
- DAWN
- Status last verified
- Oct 2014
- First submitted
- 6 Jun 2008
- Last updated
- 21 Oct 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Lantus and NPH Insulin in the Dawn Phenomenon
- ClinicalTrials.gov ID
- NCT00694122
- Acronym / sponsor ID
- DAWN / 2005-P-002515/24
- Conditions
- Type 1 Diabetes, Dawn Phenomenon
- Keywords
- glucose, cortisol, growth hormone, glucagon, insulin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Sanofi
- Study start
- Jun 2005
- Primary completion
- Nov 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 10 Jun 2008 (estimated)
- Results
- Posted 21 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- 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.
- 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
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Glargine (Lantus) insulin | Active comparator | Drug: Lantus (glargine)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. |
| NPH insulin | Active comparator | Drug: Lantus (glargine)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lantus (glargine)Also: Lantus (glargine): Sanolfi Aventis, NPH: Eli LillyDescribed in Arm Description | Drug | Glargine (Lantus) insulin, NPH insulin |
Primary outcome
Blood Glucose Area Under the Curve (AUC)
Time frame: Overnight
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
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.
4 secondary outcomes
Insulin Dose
Time frame: Overnight
Cortisol
Time frame: Overnight
Glucagon
Time frame: Overnight
Growth Hormone
Time frame: Overnight
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Type 1 Diabetes
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
RecruitingPhase 1
Pharmacokinetics, Safety, and Immunogenicity Comparison of Bmab1700 and Opdivo® as Adjuvant Monotherapy in Participants With Melanoma
Melanoma
Active, not recruitingPhase 2
A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer
Metastatic Colorectal Cancer
Not yet recruiting
Inter-Arm Differences in Continuous Glucose Monitor Readings in Adults With Diabetes
Continuous Glucose Monitoring, Type 1 Diabetes
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David M Nathan, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lantus (glargine) in people with Type 1 Diabetes and Dawn Phenomenon, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood Glucose Area Under the Curve (AUC) (time frame: Overnight). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2014.