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

• ClinicalTrials.gov Identifier: NCT01194479
• Recruitment Status: Completed
• First Posted: September 3, 2010
• Results First Posted: March 29, 2016
• Last Update Posted: March 29, 2016
• Sponsor: Yale University
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Yale University

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	Not Applicable

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 (Clinical Trial)
• 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: August 2010
• Actual Primary Completion Date: August 2014
• Actual Study Completion Date: August 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 Name: Foradil Aerolizer; Other: Placebo; Participants in both arms received placebo on 1 of the 2 visits.
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 Name: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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

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

Criteria

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

United States, Connecticut

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

More Information

Publications of Results:

Belfort-DeAguiar RD, Naik S, Hwang J, Szepietowska B, Sherwin RS. Inhaled Formoterol Diminishes Insulin-Induced Hypoglycemia in Type 1 Diabetes. Diabetes Care. 2015 Sep;38(9):1736-41. doi: 10.2337/dc14-2472. Epub 2015 Jul 7.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT01194479
• Other Study ID Numbers: HIC1005006832; R37-20495 ( Other Grant/Funding Number: NIDDK )
• First Posted: September 3, 2010
• Results First Posted: March 29, 2016
• Last Update Posted: March 29, 2016
• Last Verified: February 2016

Keywords provided by Yale University:

type 1 diabetes; hypoglycemia; formoterol

Additional relevant MeSH terms:

Diabetes Mellitus, Type 1; Hypoglycemia; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Formoterol Fumarate; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action