Glycemic Control Using Insulin Levemir Versus Insulin NPH for Diabetes in Pregnancy

• Sponsor: St. Luke's-Roosevelt Hospital Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01837680
• Collaborator: (none)
• Enrollment: 105
• Location: 1
• Arms: 2
• Duration (Months): 24
• Patients Per Site Per Month: 4.4

Study Details

Study Description

Brief Summary

The aim of this study is to compare glycemic control in pregnant women treated with insulin Detemir and pregnant women treated with NPH insulin. These women are diagnosed with gestational diabetes (GDM) in the current pregnancy or have a preexisting diagnosis of type 2 diabetes (T2DM) at the onset of pregnancy. Our hypothesis is that there is no difference between these two treatment modalities in terms of glycemic control in diabetes.

Condition or Disease	Intervention/Treatment	Phase
Diabetes, Gestational; Diabetes, Type 2	Drug: Insulin	N/A

Detailed Description

The experimental method will be a randomized controlled trial performed at Roosevelt Hospital in our Diabetes in Pregnancy Program (DIPP). Perinatologists managing the patient in DIPP determine when patients need further treatment with medical therapy. Patients undergoing care at DIPP may require medical intervention in the following clinical scenarios: failure of diet alone to control glycemic indices and grossly abnormal glucose tolerance screening test results suggesting disease of such severity that diet alone would not be sufficient. After verbally counseling the patient, she will be recruited for the study by the investigators. An extensive explanation of the objectives of the study will be presented to the patient, as well as written copies of the protocol and consent. After informed consent is given, patients will be randomized to management with either insulin NPH or detemir together with rapid acting insulin aspart (Novolog) with meals, as necessary. The primary outcome will be level of glycemic control defined as overall mean blood glucose in pregnancy. This is a well established measure of overall glycemic control that has been used in numerous publications in the obstetric literature on diabetes in pregnancy. Participants will be followed until they deliver, with an expected range of 6-16 weeks depending on when the patient was enrolled in the study. The mean glucose will be determined by the sum of average glucose at each visit divided by the number of visits).

Study Design

• Study Type: Interventional
• Actual Enrollment: 105 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Insulin Detemir Versus Insulin NPH: A Randomized Prospective Study Comparing Glycemic Control in Pregnant Women With Diabetes
• Study Start Date: Mar 1, 2013
• Actual Primary Completion Date: Mar 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Levemir Initial daily total insulin doses will be determined as per a weight based protocol depending on what trimester the patient is in. Sixty percent of the total daily insulin dose will be allotted to the morning total dose of insulin, while the remaining 40% will be allotted to the evening total dose. Of the morning dose, 2/3 will be allotted to the long acting insulin and 1/3 to short acting insulin. She will take half of the short-acting dose with breakfast and the other half with lunch. The evening insulin dose (40% of the total dose) will be divided in two: half the dose will be taken as short-acting insulin with dinner, and the other half as long acting insulin at bedtime. Doses are rounded down if decimals are present.	Drug: Insulin; Other Names: Insulin NPH Insulin Levemir
Active Comparator: NPH Initial daily total insulin doses will be determined as per a weight based protocol depending on what trimester the patient is in. Sixty percent of the total daily insulin dose will be allotted to the morning total dose of insulin, while the remaining 40% will be allotted to the evening total dose. Of the morning dose, 2/3 will be allotted to the long acting insulin and 1/3 to short acting insulin. She will get the entire dose of short-acting insulin with breakfast. The evening insulin dose (40% of the total dose) will be divided in two: half the dose will be taken as short-acting insulin with dinner, and the other half as long acting insulin at bedtime. Doses are rounded down if decimals are present.	Drug: Insulin; Other Names: Insulin NPH Insulin Levemir

Outcome Measures

Primary Outcome Measures

1. Glycemic Control [up to 41 weeks]

   Overall mean glucose value of pregnancy. This will be determined by the sum of average glucose value at each visit, divided by the number of visits.

Secondary Outcome Measures

1. Number of Patients Obtaining Glycemic Control [up to 41 weeks]

   Number of each group that obtains glycemic control, defined as mean glucose <100mg/dl.

2. Time to Achieve Glycemic Control [up to 41 weeks]

   Time (weeks) to achieve glycemic control, as defined as mean glucose <100mg/dl

3. Average Fasting Glucose [up to 41 weeks]

   Mean fasting blood glucose in pregnancy, as determined by the sum of the mean fasting glucose at each visit divided by the number of visits

4. Post-prandial Blood Glucose [up to 41 weeks]

   Mean post-prandial blood glucose in pregnancy, as defined as the sum of the average post-prandial blood glucose at each visit divided by the number of visits.

5. Weight Gain [Number of pounds gained at each visit up to 41 weeks]

   Total weight gain in pregnancy

6. Neonatal Weight [At delivery, up to 41 weeks]

   Neonatal weight was estimated for occurrence of neonatal macrosomia (≥4000g birth weight) and neonatal LGA(large for gestational age)(birth weight >90th percentile for gestational age

7. Gestational Age at Delivery [at delivery, up to 41 weeks]

   Gestational age at delivery

8. Maternal Hypoglycemia [at delivery, up to 41 weeks]

   Number of participants with incidence of maternal hypoglycemia (<60mg/dl)

9. Neonatal Bilirubin [at birth, up to 41 weeks]

   Percentage of neonatal hyperbilirubinemia - data not collected

10. Intensive Care Admissions [at birth, up to 41 weeks]

    Number of participants with incidence of neonatal intensive care unit admissions

11. Delivery Mode [at birth, up to 41 weeks]

    method of delivery including cesarean section, vaginal delivery, or assisted vaginal delivery - data not collected

12. Birth Rate [at birth, up to 41 weeks]

    Number of live birth rate

13. Shoulder Dystocia [at birth, up to 41 weeks]

    Incidence of shoulder dystocia - data not collected

14. Polyhydramnios [at each visit in pregnancy up to 41 weeks]

    Incidence of polyhydramnios (defined as amniotic fluid index (AFI)>20 or deepest vertical pocket ≥8) - data not collected

15. Neonatal Hypoglycemia [at birth, up to 41 weeks]

    Number of participants with incidence of blood sugar <40mg/dl in neonate

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion criteria:

• All pregnant women with a viable singleton or multiple gestation at ≤34 weeks with gestational diabetes diagnosed in their current pregnancy requiring medical therapy. "Early diagnosis" GDM patients will also be included; which is defined as a diagnosis made prior to 24 weeks.

• Women with known preexisting type 2 diabetes that are in need of medical therapy.

Exclusion criteria:

• Patients <18 years of age

• a diagnosis of GDM outside of the gestational age stated above

• known allergy/prior adverse reaction to insulin NPH or insulin detemir.

• type 1 diabetes

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Luke's-Roosevelt Hospital Center	New York	New York	United States	10019

Sponsors and Collaborators

• St. Luke's-Roosevelt Hospital Center

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: St. Luke's-Roosevelt Hospital Center
• ClinicalTrials.gov Identifier: NCT01837680
• Other Study ID Numbers: 12-166
• First Posted: Apr 23, 2013
• Last Update Posted: May 30, 2017
• Last Verified: May 1, 2017

• Keywords provided by St. Luke's-Roosevelt Hospital Center: Insulin, Long-Acting
• Additional relevant MeSH terms: Diabetes, Gestational; Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin; Insulin, Globin Zinc

Study Results

Participant Flow

Recruitment Details	Women with gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) who entered the Diabetes in Pregnancy Program were recruited from March 2013 through October 2014

Arm/Group Title	Insulin NPH	Levemir
Arm/Group Description	Insulin neutral protamine Hagedorn (NPH) - Current weight was obtained at the visit and initial daily total insulin dose was determined based on patient weight (in kilograms) and trimester. In the first trimester, patient weight was multiplied by 0.7, in the second trimester by 0.8, and in the third trimester by 0.9 for the total daily dose of insulin (in units). Of the total daily insulin dose, 60% was allotted to the morning total dose of insulin, while the remaining 40% allotted to the evening total dose.	Insulin detemir (IDet) - Current weight was obtained at the visit and initial daily total insulin dose was determined based on patient weight (in kilograms) and trimester. In the first trimester, patient weight was multiplied by 0.7, in the second trimester by 0.8, and in the third trimester by 0.9 for the total daily dose of insulin (in units). Of the total daily insulin dose, 60% was allotted to the morning total dose of insulin, while the remaining 40% allotted to the evening total dose.
Period Title: Overall Study
STARTED	52	53
COMPLETED	42	45
NOT COMPLETED	10	8

Baseline Characteristics

Arm/Group Title	Insulin NPH	Levemir	Total
Arm/Group Description	Insulin neutral protamine Hagedorn	Insulin detemir (IDet)	Total of all reporting groups
Overall Participants	42	45	87
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	35	35	35
Sex: Female, Male (Count of Participants)
Female	42 100%	45 100%	87 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	11 26.2%	17 37.8%	28 32.2%
Black	7 16.7%	5 11.1%	12 13.8%
Hispanic	12 28.6%	15 33.3%	27 31%
Native American/Alaskan	12 28.6%	6 13.3%	18 20.7%
Biracial/Multiracial	0 0%	0 0%	0 0%
Other	0 0%	2 4.4%	2 2.3%
T2DM (Count of Participants)
Count of Participants [Participants]	7 16.7%	7 15.6%	14 16.1%
GDM in previous pregnancies (Count of Participants)
Count of Participants [Participants]	8 19%	9 20%	17 19.5%
Multiple gestation (Count of Participants)
Count of Participants [Participants]	2 4.8%	3 6.7%	5 5.7%
Polycystic ovary syndrome (Count of Participants)
Count of Participants [Participants]	5 11.9%	12 26.7%	17 19.5%
Chronic hypertension (Count of Participants)
Count of Participants [Participants]	5 11.9%	6 13.3%	11 12.6%
Renal disease (Count of Participants)
Count of Participants [Participants]	1 2.4%	5 11.1%	6 6.9%
Thyroid disease (Count of Participants)
Count of Participants [Participants]	6 14.3%	8 17.8%	14 16.1%
Prepregnancy body mass index (kg/m^2) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg/m^2]	28.3	28.6	28.4
Prepregnancy body status (Count of Participants)
Normal	11 26.2%	14 31.1%	25 28.7%
Obese	14 33.3%	12 26.7%	26 29.9%
Overweight	12 28.6%	16 35.6%	28 32.2%
Morbidly obese	4 9.5%	3 6.7%	7 8%
Gestational age diagnosed (weeks) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [weeks]	26.1	26.6	26.3
Previous management (Count of Participants)
Diet	35 83.3%	39 86.7%	74 85.1%
Diet, Metformin	0 0%	1 2.2%	1 1.1%
Glyburide	3 7.1%	2 4.4%	5 5.7%
Metformin	3 7.1%	2 4.4%	5 5.7%
Metformin and glyburide	1 2.4%	0 0%	1 1.1%
Other type of insulin	0 0%	1 2.2%	1 1.1%
Gestational age at entry to DIPP (weeks) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [weeks]	27.3	28.1	27.5
Gestational age insulin started (weeks) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [weeks]	29.6	30.0	30.0
Time between visits (weeks) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [weeks]	1.5	1.5	1.5

Outcome Measures

1. Primary Outcome

Title	Glycemic Control
Description	Overall mean glucose value of pregnancy. This will be determined by the sum of average glucose value at each visit, divided by the number of visits.
Time Frame	up to 41 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin NPH	Levemir
Arm/Group Description	Insulin neutral protamine Hagedorn	Insulin detemir (IDet)
Measure Participants	42	45
Mean (Standard Deviation) [mg/dL]	109.5 (10.0)	107.4 (7.1)

2. Secondary Outcome

Title	Number of Patients Obtaining Glycemic Control
Description	Number of each group that obtains glycemic control, defined as mean glucose <100mg/dl.
Time Frame	up to 41 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin NPH	Levemir
Arm/Group Description	Insulin neutral protamine Hagedorn	Insulin detemir (IDet)
Measure Participants	42	45
Count of Participants [Participants]	28 66.7%	35 77.8%

3. Secondary Outcome

Title	Time to Achieve Glycemic Control
Description	Time (weeks) to achieve glycemic control, as defined as mean glucose <100mg/dl
Time Frame	up to 41 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin NPH	Levemir
Arm/Group Description	Insulin neutral protamine Hagedorn	Insulin detemir (IDet)
Measure Participants	42	45
Median (Full Range) [weeks]	5	5

4. Secondary Outcome

Title	Average Fasting Glucose
Description	Mean fasting blood glucose in pregnancy, as determined by the sum of the mean fasting glucose at each visit divided by the number of visits
Time Frame	up to 41 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin NPH	Levemir
Arm/Group Description	Insulin neutral protamine Hagedorn	Insulin detemir (IDet)
Measure Participants	42	45
Mean (Standard Deviation) [mg/dL]	100.7 (10.1)	97.3 (7.4)

5. Secondary Outcome

Title	Post-prandial Blood Glucose
Description	Mean post-prandial blood glucose in pregnancy, as defined as the sum of the average post-prandial blood glucose at each visit divided by the number of visits.
Time Frame	up to 41 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin NPH	Levemir
Arm/Group Description	Insulin neutral protamine Hagedorn	Insulin detemir (IDet)
Measure Participants	42	45
Mean (Standard Deviation) [mg/dL]	115.2 (10.2)	112.9 (8.9)

6. Secondary Outcome

Title	Weight Gain
Description	Total weight gain in pregnancy
Time Frame	Number of pounds gained at each visit up to 41 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin NPH	Levemir
Arm/Group Description	Insulin neutral protamine Hagedorn	Insulin detemir (IDet)
Measure Participants	42	45
Mean (Standard Deviation) [lbs]	27.7 (15.3)	28.6 (11.6)

7. Secondary Outcome

Title	Neonatal Weight
Description	Neonatal weight was estimated for occurrence of neonatal macrosomia (≥4000g birth weight) and neonatal LGA(large for gestational age)(birth weight >90th percentile for gestational age
Time Frame	At delivery, up to 41 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin NPH	Levemir
Arm/Group Description	Insulin neutral protamine Hagedorn	Insulin detemir (IDet)
Measure Participants	42	45
Median (Inter-Quartile Range) [g]	3230	3235

8. Secondary Outcome

Title	Gestational Age at Delivery
Description	Gestational age at delivery
Time Frame	at delivery, up to 41 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin NPH	Levemir
Arm/Group Description	Insulin neutral protamine Hagedorn	Insulin detemir (IDet)
Measure Participants	42	45
Median (Inter-Quartile Range) [weeks]	38.9	38.8

9. Secondary Outcome

Title	Maternal Hypoglycemia
Description	Number of participants with incidence of maternal hypoglycemia (<60mg/dl)
Time Frame	at delivery, up to 41 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin NPH	Levemir
Arm/Group Description	Insulin neutral protamine Hagedorn	Insulin detemir (IDet)
Measure Participants	42	45
Count of Participants [Participants]	11 26.2%	16 35.6%

10. Secondary Outcome

Title	Neonatal Bilirubin
Description	Percentage of neonatal hyperbilirubinemia - data not collected
Time Frame	at birth, up to 41 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin NPH	Levemir
Arm/Group Description	Insulin neutral protamine Hagedorn	Insulin detemir (IDet)
Measure Participants	0	0

11. Secondary Outcome

Title	Intensive Care Admissions
Description	Number of participants with incidence of neonatal intensive care unit admissions
Time Frame	at birth, up to 41 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin NPH	Levemir
Arm/Group Description	Insulin neutral protamine Hagedorn	Insulin detemir (IDet)
Measure Participants	42	45
Count of Participants [Participants]	3 7.1%	6 13.3%

12. Secondary Outcome

Title	Delivery Mode
Description	method of delivery including cesarean section, vaginal delivery, or assisted vaginal delivery - data not collected
Time Frame	at birth, up to 41 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin NPH	Levemir
Arm/Group Description	Insulin neutral protamine Hagedorn	Insulin detemir (IDet)
Measure Participants	0	0

13. Secondary Outcome

Title	Birth Rate
Description	Number of live birth rate
Time Frame	at birth, up to 41 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin NPH	Levemir
Arm/Group Description	Insulin neutral protamine Hagedorn	Insulin detemir (IDet)
Measure Participants	42	45
Count of Participants [Participants]	42 100%	45 100%

14. Secondary Outcome

Title	Shoulder Dystocia
Description	Incidence of shoulder dystocia - data not collected
Time Frame	at birth, up to 41 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin NPH	Levemir
Arm/Group Description	Insulin neutral protamine Hagedorn	Insulin detemir (IDet)
Measure Participants	0	0

15. Secondary Outcome

Title	Polyhydramnios
Description	Incidence of polyhydramnios (defined as amniotic fluid index (AFI)>20 or deepest vertical pocket ≥8) - data not collected
Time Frame	at each visit in pregnancy up to 41 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin NPH	Levemir
Arm/Group Description	Insulin neutral protamine Hagedorn	Insulin detemir (IDet)
Measure Participants	0	0

16. Secondary Outcome

Title	Neonatal Hypoglycemia
Description	Number of participants with incidence of blood sugar <40mg/dl in neonate
Time Frame	at birth, up to 41 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin NPH	Levemir
Arm/Group Description	Insulin neutral protamine Hagedorn	Insulin detemir (IDet)
Measure Participants	42	45
Count of Participants [Participants]	0 0%	2 4.4%

Adverse Events

Arm/Group Title	Insulin NPH		Levemir
Arm/Group Description	Insulin neutral protamine Hagedorn		Insulin detemir (IDet)
All Cause Mortality
	Insulin NPH		Levemir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/52 (0%)		0/53 (0%)
Serious Adverse Events
	Insulin NPH		Levemir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/52 (0%)		0/53 (0%)
Other (Not Including Serious) Adverse Events
	Insulin NPH		Levemir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/52 (51.9%)		45/53 (84.9%)
Metabolism and nutrition disorders
Symptomatic hypoglycemia	11/52 (21.2%)	28	16/53 (30.2%)	102
biochemical event of hypoglycemia	14/52 (26.9%)	26	27/53 (50.9%)	136
Symptomatic nocturnal event	2/52 (3.8%)		8/53 (15.1%)
Skin and subcutaneous tissue disorders
Rash	6/52 (11.5%)	6	0/53 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.