Effect of Formoterol on the Counterregulatory Hormonal Response to Hypoglycemia in Type 1 Diabetes.

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01194479
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 14
• Location: 1
• Arms: 2
• Duration (Months): 48
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Insulin treatment often causes the blood glucose levels to fall too low. The body usually responds to low blood glucose levels by releasing hormones which act against the insulin to help correct the low blood glucose levels. However, this hormone response can be altered in people with diabetes. Currently there are no therapeutic agents that can be used to improve the recovery from hypoglycemia (low blood sugar). The aim of this study is to determine whether a formoterol inhaler can be used to improve and accelerate the recovery from hypoglycemia in patients with type 1 diabetes.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes	Drug: Formoterol; Other: Placebo	N/A

Detailed Description

Note: Below is the original detailed description submitted in 2010. The recruitment for this study was stopped at 7 subjects in each study arm. The study design and outcome measures did not change for this study. See below for further details.

Original: 15 subjects with well controlled type 1 diabetes and regular hypoglycemia and 15 healthy volunteers will be recruited for this study.

If you agree to participate in this study, you will be asked to participate in a screening at Yale New Haven Hospital. Each study subject will undergo two hypoglycemic clamp studies (a procedure where the blood sugar is closely regulated with intravenous insulin and glucose.) In these hypoglycemic clamp studies, the subject will be given an inhaler. On one visit the inhaler will contain formoterol capsules and on the other visit, the subject will be given 'dummy' capsules. Subjects will be required to be admitted to the HRU the night before the study so that glucose levels can be stabilized and hypoglycemia avoided.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The Effect of the Beta 2 Agonist, Formoterol, on Recovery From Hypoglycemia
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Type 1 Diabetics The active group were participants with type 1 diabetes.	Drug: Formoterol; Formoterol inhaler, 12mcg capsules, 4 capsules for one administration; Other Names: Foradil Aerolizer ; Other: Placebo; Participants in both arms received placebo on 1 of the 2 visits.
Other: Healthy Volunteers The control group were participants without diabetes, matched by sex, age and BMI to the active comparator group.	Drug: Formoterol; Formoterol inhaler, 12mcg capsules, 4 capsules for one administration; Other Names: Foradil Aerolizer ; Other: Placebo; Participants in both arms received placebo on 1 of the 2 visits.

Outcome Measures

Primary Outcome Measures

1. Glucagon (pg/mL) [up to 120 minutes]

   Glucagon levels will be measured throughout the study to assess whether there are changes during hypoglycemia with inhaled formoterol. These levels will be checked every 20 minutes during the 120 minute study session. Results are presented at the Basal, Euglycemia (30 minutes) and Hypoglycemia (105-120 minutes) stages.

2. Epinephrine (pg/mL) [up to 120 minutes]

   Epinephrine levels will be measured throughout the study to assess whether there are changes during hypoglycemia with inhaled formoterol. These levels will be checked every 20 minutes during the 120 minute study session. Results are presented at the Basal, Euglycemia (30 minutes) and Hypoglycemia (105-120 minutes) stages

3. Norepinephrine (pg/mL) [up to 120 minutes]

   Norepinephrine levels will be measured throughout the study to assess whether there are changes during hypoglycemia with inhaled formoterol. These levels will be checked every 20 minutes during the 120 minute study session. Results are presented at the Basal, Euglycemia (30 minutes) and Hypoglycemia (105-120 minutes) stages

Secondary Outcome Measures

1. Blood Glucose Levels (Average) [Up to 120 minutes]

   Blood glucose levels will be checked every 5 minutes during the 120 minute study session in order to maintain blood glucose levels in the normal and hypoglycemic range. Presented is the average of the collected values.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• type 1 diabetes (well controlled, 2-3 hypoglycemic episodes/wk)

• age 18-50

• BMI 18-30

Exclusion Criteria:

• pregnancy

• significant diabetes complications

• liver disease, cirrhosis

• cardiac disease

• neurological disorder

• autonomic neuropathy

• kidney disease

• lactose intolerance

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University School of Medicine	New Haven	Connecticut	United States	06520

Sponsors and Collaborators

• Yale University
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Robert Sherwin, MD, Yale School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT01194479
• Other Study ID Numbers: HIC1005006832; R37-20495
• First Posted: Sep 3, 2010
• Last Update Posted: Mar 29, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by Yale University: type 1 diabetes; hypoglycemia; formoterol
• Additional relevant MeSH terms: Diabetes Mellitus, Type 1; Hypoglycemia; Formoterol Fumarate

Study Results

Participant Flow

Recruitment Details	Healthy subjects and Type 1 Diabetics were recruited to participate in the study. Subjects in either arm were randomized to receive a placebo or the study drug: Formoterol in either the first or second visit.

Arm/Group Title	Control: Placebo	Control: Formoterol	Type 1 Diabetics: Placebo	Type 1 Diabetics: Formoterol
Arm/Group Description	Healthy volunteers that received Placebo first, the Formoterol.	Healthy volunteers that received Formoterol first, then Placebo.	Type 1 Diabetics that received Placebo first, then Formoterol.	Type 1 Diabetics that received Formoterol first, then Placebo.
Period Title: Overall Study
STARTED	3	4	2	5
Cross-over at Second Visit	3	4	2	5
COMPLETED	3	4	2	5
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Healthy Volunteers	Type 1 Diabetics	Total
Arm/Group Description	The control group were participants without diabetes, matched by sex, age and BMI to the active comparator group. Formoterol: Formoterol inhaler, 12mcg capsules, 4 capsules for one administration Placebo: Participants in both arms received placebo on 1 of the 2 visits.	The active group were participants with type 1 diabetes. Formoterol: Formoterol inhaler, 12mcg capsules, 4 capsules for one administration Placebo: Participants in both arms received placebo on 1 of the 2 visits.	Total of all reporting groups
Overall Participants	7	7	14
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36 (8)	31 (11)	33.2 (9.7)
Sex: Female, Male (Count of Participants)
Female	4 57.1%	4 57.1%	8 57.1%
Male	3 42.9%	3 42.9%	6 42.9%
Body Mass Index (BMI, kg/m^2) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	23.7 (2.1)	25.8 (2.9)	24.8 (2.7)
Weight (kg) (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	70.0 (12.9)	70.2 (10.6)	70.1 (11.3)
HbA1c (%) (%) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [%]	5.3 (2.6)	6.8 (2.6)	6.1 (1.0)
HbA1c (mmol/mol) (mmol/mol) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/mol]	34.5 (2.6)	51.3 (8.5)	43.5 (10.7)

Outcome Measures

1. Primary Outcome

Title	Glucagon (pg/mL)
Description	Glucagon levels will be measured throughout the study to assess whether there are changes during hypoglycemia with inhaled formoterol. These levels will be checked every 20 minutes during the 120 minute study session. Results are presented at the Basal, Euglycemia (30 minutes) and Hypoglycemia (105-120 minutes) stages.
Time Frame	up to 120 minutes

Outcome Measure Data

Analysis Population Description

Results are pooled at the arm level and split by placebo and control regardless of randomization order.

Arm/Group Title	Control: Placebo	Control: Formoterol	Type 1 Diabetics: Placebo	Type 1 Diabetics: Formoterol
Arm/Group Description	Healthy volunteers that received Placebo on the first or second visit.	Healthy volunteers that received Formoterol on the first or second visit.	Type 1 Diabetics that received placebo on the first or second visit.	Type 1 Diabetics that received Formoterol on the first or second visit.
Measure Participants	7	7	7	7
Basal	76 (13)	74 (11)	53 (8)	56 (10)
Euglycemia	59 (11)	58 (13)	55 (10)	54 (9)
Hypoglycemia	66 (16)	73 (18)	43 (8)	46 (9)

2. Secondary Outcome

Title	Blood Glucose Levels (Average)
Description	Blood glucose levels will be checked every 5 minutes during the 120 minute study session in order to maintain blood glucose levels in the normal and hypoglycemic range. Presented is the average of the collected values.
Time Frame	Up to 120 minutes

Outcome Measure Data

Analysis Population Description

Subjects are pooled across randomized conditions in their respective study arms and reported overall.

Arm/Group Title	Control: Placebo	Control: Formoterol	Type 1 Diabetics: Placebo	Type 1 Diabetics: Formoterol
Arm/Group Description	Healthy volunteers that received Placebo on the first or second visit.	Healthy volunteers that received Formoterol on the first or second visit.	Type 1 Diabetics that received placebo on the first or second visit.	Type 1 Diabetics that received Formoterol on the first or second visit.
Measure Participants	7	7	7	7
Mean (Standard Deviation) [mg/dL]	57.38 (3.45)	58.39 (2.40)	53.21 (2.57)	55.43 (4.40)

3. Primary Outcome

Title	Epinephrine (pg/mL)
Description	Epinephrine levels will be measured throughout the study to assess whether there are changes during hypoglycemia with inhaled formoterol. These levels will be checked every 20 minutes during the 120 minute study session. Results are presented at the Basal, Euglycemia (30 minutes) and Hypoglycemia (105-120 minutes) stages
Time Frame	up to 120 minutes

Outcome Measure Data

Analysis Population Description

Results are pooled at the arm level and split by placebo and control regardless of randomization order.

Arm/Group Title	Control: Placebo	Control: Formoterol	Type 1 Diabetics: Placebo	Type 1 Diabetics: Formoterol
Arm/Group Description	Healthy volunteers that received Placebo on the first or second visit.	Healthy volunteers that received Formoterol on the first or second visit.	Type 1 Diabetics that received placebo on the first or second visit.	Type 1 Diabetics that received Formoterol on the first or second visit.
Measure Participants	7	7	7	7
Basal	15 (4)	16 (5)	18 (4)	17 (5)
Euglycemia	12 (3)	12 (4)	21 (5)	13 (2)
Hypoglycemia	46 (15)	55 (22)	44 (15)	19 (4)

4. Primary Outcome

Title	Norepinephrine (pg/mL)
Description	Norepinephrine levels will be measured throughout the study to assess whether there are changes during hypoglycemia with inhaled formoterol. These levels will be checked every 20 minutes during the 120 minute study session. Results are presented at the Basal, Euglycemia (30 minutes) and Hypoglycemia (105-120 minutes) stages
Time Frame	up to 120 minutes

Outcome Measure Data

Analysis Population Description

Results are pooled at the arm level and split by placebo and control regardless of randomization order.

Arm/Group Title	Control: Placebo	Control: Formoterol	Type 1 Diabetics: Placebo	Type 1 Diabetics: Formoterol
Arm/Group Description	Healthy volunteers that received Placebo on the first or second visit.	Healthy volunteers that received Formoterol on the first or second visit.	Type 1 Diabetics that received placebo on the first or second visit.	Type 1 Diabetics that received Formoterol on the first or second visit.
Measure Participants	7	7	7	7
Basal	185 (37)	192 (24)	180 (28)	133 (13)
Euglycemia	216 (31)	273 (22)	226 (31)	211 (30)
Hypoglycemia	156 (21)	181 (14)	241 (30)	190 (32)

Adverse Events

Time Frame	Adverse events are reported by the study arm and randomized visit order.
Arm/Group Title	Control: Placebo		Control: Formoterol		Type 1 Diabetics: Placebo		Type 1 Diabetics: Formoterol
Arm/Group Description	Healthy volunteers that received Placebo on the first visit.		Healthy volunteers that received Formoterol on the first visit.		Type 1 Diabetics that received placebo on the first visit.		Type 1 Diabetics that received Formoterol on the first visit.
All Cause Mortality
	Control: Placebo		Control: Formoterol		Type 1 Diabetics: Placebo		Type 1 Diabetics: Formoterol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Control: Placebo		Control: Formoterol		Type 1 Diabetics: Placebo		Type 1 Diabetics: Formoterol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/7 (0%)		0/7 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Control: Placebo		Control: Formoterol		Type 1 Diabetics: Placebo		Type 1 Diabetics: Formoterol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/7 (28.6%)		3/7 (42.9%)		0/7 (0%)		2/7 (28.6%)
Cardiac disorders
Mild Palpitations	0/7 (0%)	0	0/7 (0%)	0	0/7 (0%)	0	1/7 (14.3%)	1
General disorders
Shakiness	0/7 (0%)	0	3/7 (42.9%)	3	0/7 (0%)	0	1/7 (14.3%)	1
Hunger	1/7 (14.3%)	1	1/7 (14.3%)	1	0/7 (0%)	0	1/7 (14.3%)	1
Tiredness	1/7 (14.3%)	1	1/7 (14.3%)	1	0/7 (0%)	0	1/7 (14.3%)	1
Nervous system disorders
Light Headedness	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0	0/7 (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.