Trial Outcomes & Findings for The Glucagon Stimulation Test for Evaluation of Adult Growth Hormone Deficiency and Adrenocorticotropic Axis (NCT NCT01282164)

Results Overview

The peak growth hormone (GH) during Insulin Tolerance Test (ITT), fixed- dose glucagon stimulation test (GST) and weight-based GST in patients with adult onset hypothalamic-pituitary disease and 1-2 pituitary hormone deficiency (PHD) other than growth hormone (GH) deficiency.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

43 participants

Primary outcome timeframe

one year

Results posted on

2017-05-17

Participant Flow

A total of 28 patients with hypothalamic-pituitary disorders and 1-2 (n = 14) or 3 or more (n = 14) pituitary hormone efficiencies (PHD) were recruited from four pituitary centers. A control group of 14 subjects was also recruited and underwent the insulin tolerance test (ITT) and the two glucagon stimulation tests (GSTs).

There was no wash out period. Patients and controls were eligible for the study after the initial office visit for eligibility criteria, signing the consent form followed by labs to make sure that they are eligible for the study. One patient was excluded since the patient did not achieve hypoglycemia during insulin tolerance test

Participant milestones

Participant milestones
Measure	Study Patients patients with growth hormone deficiency or hypothalamic-pituitary disorders Glucagon stimulation test and insulin tolerance test: glucagon stimulation test using 1 mg (1.5 mg if weigh \>90 kg) glucagon stimulation test using 0.03 mg/kg (maximum dose 3 mg) insulin tolerance test using 0.10-0.15 U/kg adrenocorticotropin hormone (ACTH) stimulation test in subjects with type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), cerebrovascular disease (CVD), seizure	Control The control group will consist of healthy volunteers matched to the study group for age, gender, BMI and estrogen status. Note: Allegheny site is not enrolling in the control group. glucagon stimulation test and insulin tolerance test: glucagon stimulation test using 1 mg (1.5 mg if weigh \>90 kg) glucagon stimulation test using 0.03 mg/kg (maximum dose 3 mg) insulin tolerance test using 0.10-0.15 U/kg ACTH stimulation test in subjects with T2DM, CAD, CVD, seizure
Overall Study STARTED	29	14
Overall Study COMPLETED	28	14
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Study Patients patients with growth hormone deficiency or hypothalamic-pituitary disorders Glucagon stimulation test and insulin tolerance test: glucagon stimulation test using 1 mg (1.5 mg if weigh \>90 kg) glucagon stimulation test using 0.03 mg/kg (maximum dose 3 mg) insulin tolerance test using 0.10-0.15 U/kg adrenocorticotropin hormone (ACTH) stimulation test in subjects with type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), cerebrovascular disease (CVD), seizure	Control The control group will consist of healthy volunteers matched to the study group for age, gender, BMI and estrogen status. Note: Allegheny site is not enrolling in the control group. glucagon stimulation test and insulin tolerance test: glucagon stimulation test using 1 mg (1.5 mg if weigh \>90 kg) glucagon stimulation test using 0.03 mg/kg (maximum dose 3 mg) insulin tolerance test using 0.10-0.15 U/kg ACTH stimulation test in subjects with T2DM, CAD, CVD, seizure
Overall Study Lack of hypoglycemia during ITT	1	0

Baseline Characteristics

The Glucagon Stimulation Test for Evaluation of Adult Growth Hormone Deficiency and Adrenocorticotropic Axis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Study Patients n=28 Participants patients with growth hormone deficiency or hypothalamic-pituitary disorders Glucagon stimulation test and insulin tolerance test: glucagon stimulation test using 1 mg (1.5 mg if weigh \>90 kg) glucagon stimulation test using 0.03 mg/kg (maximum dose 3 mg) insulin tolerance test using 0.10-0.15 U/kg ACTH stimulation test in subjects with T2DM, CAD, CVD, seizure	Control n=14 Participants The control group will consist of healthy volunteers matched to the study group for age, gender, BMI and estrogen status. Note: Allegheny site is not enrolling in the control group. glucagon stimulation test and insulin tolerance test: glucagon stimulation test using 1 mg (1.5 mg if weigh \>90 kg) glucagon stimulation test using 0.03 mg/kg (maximum dose 3 mg) insulin tolerance test using 0.10-0.15 U/kg ACTH stimulation test in subjects with T2DM, CAD, CVD, seizure	Total n=42 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	25 Participants n=5 Participants	14 Participants n=7 Participants	39 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Age, Continuous	51.0 years STANDARD_DEVIATION 11.9 • n=5 Participants	49.0 years STANDARD_DEVIATION 12.2 • n=7 Participants	50.3 years STANDARD_DEVIATION 11.9 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	8 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	6 Participants n=7 Participants	20 Participants n=5 Participants
Region of Enrollment United States	28 Participants n=5 Participants	14 Participants n=7 Participants	42 Participants n=5 Participants

PRIMARY outcome

Timeframe: one year

Population: Peak GH levels during Insulin Tolerance test, fixed-dose GST and weight-based GST in Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency other than GH deficiency. One patient older than 65 years underwent adrenocorticotropin hormone (ACTH) stimulation test instead of ITT.

The peak growth hormone (GH) during Insulin Tolerance Test (ITT), fixed- dose glucagon stimulation test (GST) and weight-based GST in patients with adult onset hypothalamic-pituitary disease and 1-2 pituitary hormone deficiency (PHD) other than growth hormone (GH) deficiency.

Outcome measures

Outcome measures
Measure	Patients With 1-2 PHD- Insulin Tolerance Test n=13 Participants Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency insulin tolerance test using 0.10-0.15 U/kg ACTH stimulation test was used in 3 subjects who were not eligible for ITT	Patients With 1-2 PHD- Fixed Dose GST n=14 Participants Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency	Patients With 1-2 PHD- Weight Based GST n=14 Participants Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency
Peak GH Level in Adult Patients With Hypothalamic-pituitary Disorders and 1-2 Pituitary Hormone Deficiency (PHD).	0.9 ng/mL Interval 0.2 to 18.8	0.6 ng/mL Interval 0.1 to 6.9	0.7 ng/mL Interval 0.1 to 11.7

PRIMARY outcome

Timeframe: one year

The peak growth hormone (GH) during Insulin Tolerance Test (ITT), fixed- dose glucagon stimulation test (GST) and weight-based GST in healthy volunteers

Outcome measures

Outcome measures
Measure	Patients With 1-2 PHD- Insulin Tolerance Test n=14 Participants Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency insulin tolerance test using 0.10-0.15 U/kg ACTH stimulation test was used in 3 subjects who were not eligible for ITT	Patients With 1-2 PHD- Fixed Dose GST n=14 Participants Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency	Patients With 1-2 PHD- Weight Based GST n=14 Participants Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency
Peak Growth Hormone (GH) Level in Healthy Volunteers	14.0 ng/mL Interval 2.5 to 42.7	4.5 ng/mL Interval 1.3 to 11.3	5.8 ng/mL Interval 2.3 to 24.5

PRIMARY outcome

Timeframe: one year

Population: Peak GH levels during Insulin Tolerance test, fixed-dose GST and weight-based GST in Patients with hypothalamic-pituitary disorders with three or more pituitary hormone deficiency other than GH deficiency. Two patients older than 65 years underwent adrenocorticotropin hormone (ACTH) stimulation test instead of ITT.

The peak growth hormone (GH) during Insulin Tolerance Test (ITT), fixed- dose glucagon stimulation test (GST) and weight-based GST in patients with adult onset hypothalamic-pituitary disease with three or more pituitary hormone deficiency (PHD) other than growth hormone (GH) deficiency.

Outcome measures

Outcome measures
Measure	Patients With 1-2 PHD- Insulin Tolerance Test n=12 Participants Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency insulin tolerance test using 0.10-0.15 U/kg ACTH stimulation test was used in 3 subjects who were not eligible for ITT	Patients With 1-2 PHD- Fixed Dose GST n=14 Participants Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency	Patients With 1-2 PHD- Weight Based GST n=14 Participants Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency
Peak GH Level in Adult Patients With Hypothalamic-pituitary Disorders and Three or More Pituitary Hormone Deficiency (PHD).	0.1 ng/mL Interval 0.1 to 4.4	0.1 ng/mL Interval 0.1 to 2.8	0.1 ng/mL Interval 0.1 to 2.1

PRIMARY outcome

Timeframe: one year

Population: Peak cortisol levels during Insulin Tolerance test, fixed-dose GST and weight-based GST in Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency other than GH deficiency. One patient older than 65 years of age underwent ACTH stimulation test instead of ITT

The peak cortisol level during Insulin Tolerance Test (ITT), fixed- dose glucagon stimulation test (GST) and weight-based GST in patients with adult onset hypothalamic-pituitary disease and 1-2 pituitary hormone deficiency (PHD) other than growth hormone (GH) deficiency.

Outcome measures

Outcome measures
Measure	Patients With 1-2 PHD- Insulin Tolerance Test n=13 Participants Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency insulin tolerance test using 0.10-0.15 U/kg ACTH stimulation test was used in 3 subjects who were not eligible for ITT	Patients With 1-2 PHD- Fixed Dose GST n=14 Participants Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency	Patients With 1-2 PHD- Weight Based GST n=14 Participants Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency
Peak Cortisol Level in Adult Patients With Hypothalamic-pituitary Disorders and 1-2 Pituitary Hormone Deficiency (PHD).	22.2 ug/dL Interval 18.6 to 29.3	19.5 ug/dL Interval 12.5 to 32.4	22.7 ug/dL Interval 15.4 to 32.2

PRIMARY outcome

Timeframe: one year

Population: Peak cortisol levels during Insulin Tolerance test, fixed-dose GST and weight-based GST in healthy volunteers

The peak cortisol levels during Insulin Tolerance Test (ITT), fixed- dose glucagon stimulation test (GST) and weight-based GST in healthy volunteers.

Outcome measures

Outcome measures
Measure	Patients With 1-2 PHD- Insulin Tolerance Test n=14 Participants Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency insulin tolerance test using 0.10-0.15 U/kg ACTH stimulation test was used in 3 subjects who were not eligible for ITT	Patients With 1-2 PHD- Fixed Dose GST n=14 Participants Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency	Patients With 1-2 PHD- Weight Based GST n=14 Participants Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency
Peak Cortisol Level in Healthy Volunteers.	22.1 ug/dL Interval 18.1 to 28.5	18.0 ug/dL Interval 11.5 to 26.7	22.7 ug/dL Interval 13.8 to 31.4

PRIMARY outcome

Timeframe: one year

Population: Peak cortisol level during Insulin Tolerance test, fixed-dose GST and weight-based GST in Patients with hypothalamic-pituitary disorders with three or more pituitary hormone deficiency other than GH deficiency. Two patients older than 65 years of age underwent adrenocorticotropin hormone (ACTH) stimulation test instead of ITT.

The peak cortisol level during Insulin Tolerance Test (ITT), fixed- dose glucagon stimulation test (GST) and weight-based GST in patients with adult onset hypothalamic-pituitary disease and three or more pituitary hormone deficiency (PHD) other than growth hormone (GH) deficiency.

Outcome measures

Outcome measures
Measure	Patients With 1-2 PHD- Insulin Tolerance Test n=12 Participants Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency insulin tolerance test using 0.10-0.15 U/kg ACTH stimulation test was used in 3 subjects who were not eligible for ITT	Patients With 1-2 PHD- Fixed Dose GST n=14 Participants Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency	Patients With 1-2 PHD- Weight Based GST n=14 Participants Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency
Peak Cortisol Level in Adult Patients With Hypothalamic-pituitary Disorders and Three or More Pituitary Hormone Deficiency (PHD).	6.3 ug/dL Interval 1.0 to 18.0	2.3 ug/dL Interval 1.0 to 16.9	2.5 ug/dL Interval 1.0 to 19.7

PRIMARY outcome

Timeframe: one year

Population: Peak cortisol level during ACTH stimulation test in three patients with hypothalamic-pituitary disorders who were older than 65 and could not undergo ITT based on the study protocol

The peak cortisol level during ACTH stimulation test in 3 patients with adult onset hypothalamic-pituitary disease who were older than 65 years of age and could not under go insulin tolerance test (ITT).

Outcome measures

Outcome measures
Measure	Patients With 1-2 PHD- Insulin Tolerance Test n=3 Participants Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency insulin tolerance test using 0.10-0.15 U/kg ACTH stimulation test was used in 3 subjects who were not eligible for ITT	Patients With 1-2 PHD- Fixed Dose GST Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency	Patients With 1-2 PHD- Weight Based GST Patients with hypothalamic-pituitary disorders and 1-2 pituitary hormone deficiency (PHD) other than GH deficiency
Peak Cortisol Level During Adrenocorticotropin Hormone (ACTH) Stimulation Test	10 ug/dL Interval 1.2 to 23.5	—	—

Adverse Events

Study Patients

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Control

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Study Patients n=28 participants at risk patients with hypothalamic-pituitary disorders Glucagon stimulation test and insulin tolerance test: glucagon stimulation test using 1 mg (1.5 mg if weigh \>90 kg) glucagon stimulation test using 0.03 mg/kg (maximum dose 3 mg) insulin tolerance test using 0.10-0.15 U/kg ACTH stimulation test in subjects with T2DM, CAD, CVD, seizure	Control n=14 participants at risk The control group will consist of healthy volunteers matched to the study group for age, gender, BMI and estrogen status. Note: Allegheny site is not enrolling in the control group. glucagon stimulation test and insulin tolerance test: glucagon stimulation test using 1 mg (1.5 mg if weigh \>90 kg) glucagon stimulation test using 0.03 mg/kg (maximum dose 3 mg) insulin tolerance test using 0.10-0.15 U/kg ACTH stimulation test in subjects with T2DM, CAD, CVD, seizure
Gastrointestinal disorders Nausea	35.7% 10/28 • Number of events 13 • 3 years Observation during dynamic testing and follow up telephone call	35.7% 5/14 • Number of events 9 • 3 years Observation during dynamic testing and follow up telephone call
Gastrointestinal disorders Vomiting	7.1% 2/28 • Number of events 3 • 3 years Observation during dynamic testing and follow up telephone call	7.1% 1/14 • Number of events 2 • 3 years Observation during dynamic testing and follow up telephone call
Nervous system disorders Headache	7.1% 2/28 • Number of events 3 • 3 years Observation during dynamic testing and follow up telephone call	7.1% 1/14 • Number of events 2 • 3 years Observation during dynamic testing and follow up telephone call
Nervous system disorders Dizziness	7.1% 2/28 • Number of events 3 • 3 years Observation during dynamic testing and follow up telephone call	14.3% 2/14 • Number of events 3 • 3 years Observation during dynamic testing and follow up telephone call

Additional Information

Dr. Amir H. Hamrahian

Cleveland Clinic

Phone: 216-445-8555

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place