Type 1 Diabetes
Conditions
Keywords
type 1 diabetes, hypoglycemia, formoterol
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.
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.
Interventions
DRUGFormoterol
Formoterol inhaler, 12mcg capsules, 4 capsules for one administration
OTHERPlacebo
Participants in both arms received placebo on 1 of the 2 visits.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
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.
Participants by arm
| Arm | Count |
|---|---|
| Healthy Volunteers 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. | 7 |
| Type 1 Diabetics 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. | 7 |
| Total | 14 |
Baseline characteristics
| Characteristic | Healthy Volunteers | Type 1 Diabetics | Total |
|---|---|---|---|
| Age, Continuous | 36 years STANDARD_DEVIATION 8 | 31 years STANDARD_DEVIATION 11 | 33.2 years STANDARD_DEVIATION 9.7 |
| Body Mass Index (BMI, kg/m^2) | 23.7 kg/m^2 STANDARD_DEVIATION 2.1 | 25.8 kg/m^2 STANDARD_DEVIATION 2.9 | 24.8 kg/m^2 STANDARD_DEVIATION 2.7 |
| HbA1c (%) | 5.3 % STANDARD_DEVIATION 2.6 | 6.8 % STANDARD_DEVIATION 2.6 | 6.1 % STANDARD_DEVIATION 1 |
| HbA1c (mmol/mol) | 34.5 mmol/mol STANDARD_DEVIATION 2.6 | 51.3 mmol/mol STANDARD_DEVIATION 8.5 | 43.5 mmol/mol STANDARD_DEVIATION 10.7 |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
| Weight (kg) | 70.0 kg STANDARD_DEVIATION 12.9 | 70.2 kg STANDARD_DEVIATION 10.6 | 70.1 kg STANDARD_DEVIATION 11.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 7 | 3 / 7 | 0 / 7 | 2 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 | 0 / 7 | 0 / 7 |
Outcome results
Primary
Epinephrine (pg/mL)
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
Population: Results are pooled at the arm level and split by placebo and control regardless of randomization order.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control: Placebo | Epinephrine (pg/mL) | Basal | 15 pg/mL | Standard Error 4 |
| Control: Placebo | Epinephrine (pg/mL) | Hypoglycemia | 46 pg/mL | Standard Error 15 |
| Control: Placebo | Epinephrine (pg/mL) | Euglycemia | 12 pg/mL | Standard Error 3 |
| Control: Formoterol | Epinephrine (pg/mL) | Basal | 16 pg/mL | Standard Error 5 |
| Control: Formoterol | Epinephrine (pg/mL) | Hypoglycemia | 55 pg/mL | Standard Error 22 |
| Control: Formoterol | Epinephrine (pg/mL) | Euglycemia | 12 pg/mL | Standard Error 4 |
| Type 1 Diabetics: Placebo | Epinephrine (pg/mL) | Euglycemia | 21 pg/mL | Standard Error 5 |
| Type 1 Diabetics: Placebo | Epinephrine (pg/mL) | Basal | 18 pg/mL | Standard Error 4 |
| Type 1 Diabetics: Placebo | Epinephrine (pg/mL) | Hypoglycemia | 44 pg/mL | Standard Error 15 |
| Type 1 Diabetics: Formoterol | Epinephrine (pg/mL) | Basal | 17 pg/mL | Standard Error 5 |
| Type 1 Diabetics: Formoterol | Epinephrine (pg/mL) | Hypoglycemia | 19 pg/mL | Standard Error 4 |
| Type 1 Diabetics: Formoterol | Epinephrine (pg/mL) | Euglycemia | 13 pg/mL | Standard Error 2 |
Primary
Glucagon (pg/mL)
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
Population: Results are pooled at the arm level and split by placebo and control regardless of randomization order.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control: Placebo | Glucagon (pg/mL) | Basal | 76 pg/mL | Standard Error 13 |
| Control: Placebo | Glucagon (pg/mL) | Hypoglycemia | 66 pg/mL | Standard Error 16 |
| Control: Placebo | Glucagon (pg/mL) | Euglycemia | 59 pg/mL | Standard Error 11 |
| Control: Formoterol | Glucagon (pg/mL) | Basal | 74 pg/mL | Standard Error 11 |
| Control: Formoterol | Glucagon (pg/mL) | Hypoglycemia | 73 pg/mL | Standard Error 18 |
| Control: Formoterol | Glucagon (pg/mL) | Euglycemia | 58 pg/mL | Standard Error 13 |
| Type 1 Diabetics: Placebo | Glucagon (pg/mL) | Euglycemia | 55 pg/mL | Standard Error 10 |
| Type 1 Diabetics: Placebo | Glucagon (pg/mL) | Basal | 53 pg/mL | Standard Error 8 |
| Type 1 Diabetics: Placebo | Glucagon (pg/mL) | Hypoglycemia | 43 pg/mL | Standard Error 8 |
| Type 1 Diabetics: Formoterol | Glucagon (pg/mL) | Basal | 56 pg/mL | Standard Error 10 |
| Type 1 Diabetics: Formoterol | Glucagon (pg/mL) | Hypoglycemia | 46 pg/mL | Standard Error 9 |
| Type 1 Diabetics: Formoterol | Glucagon (pg/mL) | Euglycemia | 54 pg/mL | Standard Error 9 |
Primary
Norepinephrine (pg/mL)
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
Population: Results are pooled at the arm level and split by placebo and control regardless of randomization order.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control: Placebo | Norepinephrine (pg/mL) | Basal | 185 pg/mL | Standard Error 37 |
| Control: Placebo | Norepinephrine (pg/mL) | Hypoglycemia | 156 pg/mL | Standard Error 21 |
| Control: Placebo | Norepinephrine (pg/mL) | Euglycemia | 216 pg/mL | Standard Error 31 |
| Control: Formoterol | Norepinephrine (pg/mL) | Basal | 192 pg/mL | Standard Error 24 |
| Control: Formoterol | Norepinephrine (pg/mL) | Euglycemia | 273 pg/mL | Standard Error 22 |
| Control: Formoterol | Norepinephrine (pg/mL) | Hypoglycemia | 181 pg/mL | Standard Error 14 |
| Type 1 Diabetics: Placebo | Norepinephrine (pg/mL) | Euglycemia | 226 pg/mL | Standard Error 31 |
| Type 1 Diabetics: Placebo | Norepinephrine (pg/mL) | Basal | 180 pg/mL | Standard Error 28 |
| Type 1 Diabetics: Placebo | Norepinephrine (pg/mL) | Hypoglycemia | 241 pg/mL | Standard Error 30 |
| Type 1 Diabetics: Formoterol | Norepinephrine (pg/mL) | Hypoglycemia | 190 pg/mL | Standard Error 32 |
| Type 1 Diabetics: Formoterol | Norepinephrine (pg/mL) | Basal | 133 pg/mL | Standard Error 13 |
| Type 1 Diabetics: Formoterol | Norepinephrine (pg/mL) | Euglycemia | 211 pg/mL | Standard Error 30 |
Secondary
Blood Glucose Levels (Average)
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
Population: Subjects are pooled across randomized conditions in their respective study arms and reported overall.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control: Placebo | Blood Glucose Levels (Average) | 57.38 mg/dL | Standard Deviation 3.45 |
| Control: Formoterol | Blood Glucose Levels (Average) | 58.39 mg/dL | Standard Deviation 2.4 |
| Type 1 Diabetics: Placebo | Blood Glucose Levels (Average) | 53.21 mg/dL | Standard Deviation 2.57 |
| Type 1 Diabetics: Formoterol | Blood Glucose Levels (Average) | 55.43 mg/dL | Standard Deviation 4.4 |