Use of Terbutaline or a Reduction in Basal Insulin in the Prevention of Nocturnal Hypoglycemia

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT00974051
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arms: 3
• Duration (Months): 9
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

The investigators hypothesize that the use of an oral dose of Terbutaline or a 20% basal reduction will be able to prevent nocturnal hypoglycemia after an afternoon exercise session. This is a randomized three period cross-over study including treatment with Terbutaline, a 20% basal reduction for six hours, or no treatment (control).

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes	Drug: Terbutaline; Other: 20% basal insulin reduction; Other: Control	N/A

Detailed Description

In this study, a minimum of 16 youth with type 1 diabetes will be recruited. All subjects must have been diagnosed with type 1 diabetes for at least one year and on an insulin pump for at least one month. Subjects are between the ages of 10 and 17 years, inclusive, have an HbA1c less than 10.0% and normal thyroid function. Subjects can not have had a severe hypoglycemic episode in the last three months, any other illness or treatment that may affect the wearing of a continuous glucose monitor or the completion of the study as determined by the investigator. Subjects may not use drugs containing pseudoephedrine within 48 hours of the study visits.

This study consists of three overnight visits at the Clinical Translational Research Center. Meals eaten during the study will be consistent for each of the three visits.

Subjects will participate in a standardized afternoon exercise session on a treadmill as has been done in previous Diabetes Research in Children Network studies. Exercise will begin at 4pm and must be completed by 6pm. Dinner will be eaten at the end of the exercise.

At 9pm, treatment will be given as determined by the randomization group the subject is assigned to. The treatment includes either an oral dose of 2.5mg Terbutaline, a 20% basal reduction for six hours or no treatment as the control. Blood glucose levels will be measured every 30 minutes until 6am.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Effect of Using Terbutaline or a Reduction in Basal Insulin Infusion as a Therapeutic Agent to Prevent Delayed Nocturnal Hypoglycemia in Children and Adolescents With Type 1 Diabetes
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Control Subjects complete the same exercise routine, however no treatment is given at 9:00pm.	Other: Control; No treatment is given for the study. This arm is for comparison with the two intervention arms.; Other Names: No intervention
Experimental: Terbutaline Subjects complete same exercise routine. At 9:00pm, an oral dose of 2.5 mg of Terbutaline is administered.	Drug: Terbutaline; Oral (2.5mg) one time administration at 9:00pm; Other Names: β2-adrenergic agonist
Experimental: 20% Basal Insulin Reduction All subjects complete the same exercise session. At 9:00pm, subject's basal rate is decreased by 20% for six hours.	Other: 20% basal insulin reduction; Basal insulin rate is reduced by 20% the normal (home dose) for six hours.; Other Names: 80% basal insulin

Outcome Measures

Primary Outcome Measures

1. Blood Glucose Nadir [overnight hours]

   BG nadir overnight after intervention

Secondary Outcome Measures

1. Percent of Nighttime Glucose Levels <80 [9:00pm to 6:00am]

2. Percent of Nighttime Glucose Levels <70 [10:00pm to 6:00am]

3. Percent of Nighttime Glucose Levels >250 mg/dl [10:00pm to 6:00am]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Clinical diagnosis of Type 1 Diabetes and using daily insulin therapy for at least one year.

• Age 10 to 17 years, inclusive.

• HbA1c < 10.0%.

• BMI 5-95th % for age and gender.

• Stable Continuous Subcutaneous Insulin Infusion regimen for at least 1 month and not anticipating a change prior to the subject's completion of the study.

• Subject uses a downloadable insulin pump.

• Normal thyroid function (measured within the previous year).

• For females, subject not intending to become pregnant during the study.

• No expectation that subject will be moving out of the area for the duration of the study.

• Informed consent form signed and understood by the parent/guardian and Child Assent form signed/understood by subjects.

Exclusion Criteria:

• The presence of a significant medical disorder (including epilepsy, or any cause of seizures other than hypoglycemia) that in the judgment of the investigator will affect the wearing of the sensors or the completion of any aspect of the protocol.

• A recent injury to body or limb, Addison's disease, muscular disorder or disease in the judgment of the investigator that will affect the completion of the exercise protocol.

• Asthma which has been medically treated within the last year.

• Medically diagnosed cardiac disease, hypertension, or autonomic dysfunction.

• Use of pseudoephedrine 48 hours prior to the visit (if used in the 48 hours prior to the scheduled visit, the visit will be deferred)

• Severe hypoglycemia resulting in seizure of loss of consciousness in the 3 months prior to a visit.

• Active infection (if at the time of the scheduled visit and infection is present, the visit will be deferred).

• Anticipating a significant change in exercise regimen between visits (i.e. starting or stopping an organized sport).

• Treatment with systemic or inhaled corticosteroids in the last 6 months.

• Current treatment with B-blockers or presenting with high blood pressure.

• Inpatient psychiatric treatment in the past 6 months for either the subject or the subject's primary care giver.

• Current use of oral/inhaled glucocorticoids or other medications, which in the judgment of the investigator would be a contraindication to participation in the study

• Known allergy to Terbutaline

• Treatment with atenolol (Tenormin), carteolol (Cartrol), labetalol (Normodyne, Trandate), metoprolol (Lopressor), nadolol (Corgard), phenelzine (Nardil), propranolol (Inderal), sotalol (Betapace), theophylline (Theo-Dur), timolol (Blocadren), tranylcypromine (Parnate), other medications for asthma, heart disease or depression.

• Treatment with ephedrine, phenylephrine, phenylpropanolamine, or pseudoephedrine.

• The presence of an irregular heart beat, increased heart rate glaucoma or an overactive thyroid gland.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barbara Davis Center	Aurora	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver

Investigators

• Principal Investigator: Rosanna Fiallo-Scharer, MD, University of Colorado, Denver

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT00974051
• Other Study ID Numbers: 07-0392
• First Posted: Sep 10, 2009
• Last Update Posted: Oct 11, 2013
• Last Verified: Aug 1, 2013

• Keywords provided by University of Colorado, Denver: Children; Exercise; Hypoglycemia
• Additional relevant MeSH terms: Diabetes Mellitus, Type 1; Hypoglycemia; Insulin; Insulin, Globin Zinc; Terbutaline; Adrenergic Agonists

Study Results

Participant Flow

Recruitment Details	Recruited from the Barbara Davis Center pediatric population
Pre-assignment Detail	no notes

Arm/Group Title	Control First, Then Terbutaline, Then 20% Basal Reduction	Terbutaline First, Then 20% Basal Reduction, Then Control	20% Basal Reduction First, Then Control, Then Terbutaline
Arm/Group Description	Subjects complete the same exercise routine. No treatment is given during the Control night, Terbutaline is given at 9pm during the Terbutaline night, a 20% basal reduction is done starting at 9pm for six hours on the 20% basal reduction night.	Subjects complete the same exercise routine. No treatment is given during the Control night, Terbutaline is given at 9pm during the Terbutaline night, a 20% basal reduction is done starting at 9pm for six hours on the 20% basal reduction night.	Subjects complete the same exercise routine. No treatment is given during the Control night, Terbutaline is given at 9pm during the Terbutaline night, a 20% basal reduction is done starting at 9pm for six hours on the 20% basal reduction night.
Period Title: Overall Study
STARTED	6	4	6
COMPLETED	6	4	6
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	All Study Subjects
Arm/Group Description	Subjects complete the same exercise routine. Subjects serve as there own control and participate in all interventions. No treatment is given during the Control night, Terbutaline is given at 9pm during the Terbutaline night, a 20% basal reduction is done starting at 9pm for six hours on the 20% basal reduction night.
Overall Participants	16
Age (Count of Participants)
<=18 years	16 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.3 (1.8)
Sex: Female, Male (Count of Participants)
Female	7 43.8%
Male	9 56.3%
Region of Enrollment (participants) [Number]
United States	16 100%

Outcome Measures

1. Secondary Outcome

Title	Percent of Nighttime Glucose Levels <80
Time Frame	9:00pm to 6:00am

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control Arm	Terbutaline Arm	20% Basal Reduction Arm
Arm/Group Description	No treatment is given during the Control night. Glucose levels from 9 pm to 6 am are analyzed.	2.5 mg oral terbutaline is given at 9pm during the Terbutaline night. Glucose levels from 9 pm to 6 am are analyzed.	Subjects complete the same exercise routine. A 20% basal reduction is done starting at 9pm for six hours on the 20% basal reduction night. Glucose levels from 9 pm to 6 am are analyzed.
Measure Participants	16	16	16
Number [percentage of overnight glucose levels]	6.6	0	4.9

2. Secondary Outcome

Title	Percent of Nighttime Glucose Levels <70
Time Frame	10:00pm to 6:00am

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control Arm	Terbutaline Arm	20% Basal Reduction Arm
Arm/Group Description	No treatment is given during the Control night. Glucose levels from 9 pm to 6 am are analyzed.	2.5 mg oral terbutaline is given at 9pm during the Terbutaline night. Glucose levels from 9 pm to 6 am are analyzed.	Subjects complete the same exercise routine. A 20% basal reduction is done starting at 9pm for six hours on the 20% basal reduction night. Glucose levels from 9 pm to 6 am are analyzed.
Measure Participants	16	16	16
Number [percentage of nighttime glucose values]	1.7	0	0.3

3. Secondary Outcome

Title	Percent of Nighttime Glucose Levels >250 mg/dl
Time Frame	10:00pm to 6:00am

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control Arm	Terbutaline Arm	20% Basal Reduction Arm
Arm/Group Description	No treatment is given during the Control night. Glucose levels from 9 pm to 6 am are analyzed.	2.5 mg oral terbutaline is given at 9pm during the Terbutaline night. Glucose levels from 9 pm to 6 am are analyzed.	Subjects complete the same exercise routine. A 20% basal reduction is done starting at 9pm for six hours on the 20% basal reduction night. Glucose levels from 9 pm to 6 am are analyzed.
Measure Participants	16	16	16
Number [percentage of overnght glucose values]	30.2	63.5	41.7

4. Primary Outcome

Title	Blood Glucose Nadir
Description	BG nadir overnight after intervention
Time Frame	overnight hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control Arm	Terbutaline Arm	20% Basal Reduction Arm
Arm/Group Description	No treatment is given during the Control night. Glucose levels from 9 pm to 6 am are analyzed.	2.5 mg oral terbutaline is given at 9pm during the Terbutaline night. Glucose levels from 9 pm to 6 am are analyzed.	Subjects complete the same exercise routine. A 20% basal reduction is done starting at 9pm for six hours on the 20% basal reduction night. Glucose levels from 9 pm to 6 am are analyzed.
Measure Participants	16	16	16
Mean (Standard Deviation) [mg/dl]	128 (58)	189 (60)	162 (65)

Adverse Events

Arm/Group Title	All Study Subjects		Control Arm		Terbutaline Arm		20% Basal Reduction Arm
Arm/Group Description	Subjects complete the same exercise routine. Subjects serve as there own control and participate in all interventions. No treatment is given during the Control night, Terbutaline is given at 9pm during the Terbutaline night, a 20% basal reduction is done starting at 9pm for six hours on the 20% basal reduction night.		during control intervention night		During turbutaline intervention night		During 20% basal reduction night
All Cause Mortality
	All Study Subjects		Control Arm		Terbutaline Arm		20% Basal Reduction Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	All Study Subjects		Control Arm		Terbutaline Arm		20% Basal Reduction Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	All Study Subjects		Control Arm		Terbutaline Arm		20% Basal Reduction Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)		0/16 (0%)		0/16 (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.