Growth Hormone Feedback to Insulin-like Growth Factor-I (IGF-1) and Oral Glucose Tolerance Test (OGTT)
Growth Hormone Feedback In Patients With Acromegaly, Type 2 Diabetes Mellitus, And Healthy Adults
1 other identifier
interventional
28
1 country
1
Brief Summary
Growth hormone (GH) and Insulin-like growth factor-I (IGF-I) secretion are altered in acromegaly and type 2 Diabetes Mellitis (DM). The secretion of GH is mediated by central hypothalamic hormones (GH Releasing Hormone and somatostatin) as well as peripheral factors providing feedback inhibition (IGF-I and glucose, among others). The purpose of this study is to compare growth hormone suppression after an oral glucose tolerance test (OGTT) to growth hormone suppression after recombinant human IGF-I (rhIGF-I) administration. This study will recruit participants with active acromegaly, type 2 diabetes mellitus, and healthy control subjects. Each participant will undergo a screening evaluation, and three subsequent visits. Each participant will receive a placebo subcutaneous injection, OGTT, and administration of rhIGF-I, on separate visit days. Glucose, insulin, GH, bioactive IGF-I and IGF-I binding proteins will be measured after each intervention. Results will be compared between the three groups. It is predicted that the administration of rhIGF-I will demonstrate GH suppression in all healthy subjects and subjects with type 2DM. Some acromegaly subjects may demonstrate GH suppression in response to IGF-I administration, but not to the degree seen in healthy subjects or type 2 DM. OGTT will demonstrate suppression of GH in normal subjects, and will show attenuated suppression in type 2 DM and a failure of suppression in acromegaly.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable
Started Dec 2008
Longer than P75 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2008
CompletedFirst Submitted
Initial submission to the registry
June 5, 2009
CompletedFirst Posted
Study publicly available on registry
June 8, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2014
CompletedResults Posted
Study results publicly available
July 9, 2019
CompletedJuly 9, 2019
July 1, 2019
4.7 years
June 5, 2009
April 2, 2019
July 7, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage With Growth Hormone (GH) Suppression to < 0.4 ng/ml
Subjects underwent recombinant insulin like growth factor 1 (rhIGF1) suppression testing and growth hormone levels were measured at time 0, 15, 30, 60, 90, 120, and 180 minutes after injection of rhIGF-1. A response \</= 0.4 ng/ml is considered a normal response in the healthy control and diabetic control subjects. The percentage of subjects with a normal GH suppression to \</= 0.4 ng/ml was calculated.
Before injection and at time 15, 30, 60, 90, 120 and 180 minutes after rhIGF-1 injection on week 4
Secondary Outcomes (3)
Median Insulin Like Growth Factor Binding Protein 1 (IGFBP-1) Area Under the Curve in Response to Placebo, Oral Glucose Tolerance Test (OGTT), and rhIGF1 Suppression Testing
Before injection at time 0 and then at 15, 30, 60, 90, 120, and 180 minutes after injection for week 2, 3, and 4 for each cohort for placebo, OGTT, and rhIGF1, respectively.
Median Insulin Level in Response to Placebo, OGTT, and rhIGF1 Testing
Measured at 120 minutes after injection for week 2, 3, and 4 for each cohort for placebo, OGTT, and rhIGF1, respectively.
Median Bioactive IGF-1 Area Under the Curve in Response to Placebo, OGTT, and rhIGF1 Testing
Before injection at time 0 and then at 15, 30, 60, 90, 120, and 180 minutes after injection for week 2, 3, and 4 for each cohort for placebo, OGTT, and rhIGF1, respectively.
Study Arms (3)
Active Acromegaly
ACTIVE COMPARATORPlacebo, oral glucose tolerance test, and subcutaneous administration of recombinant human IGF-1 will be given at visits 2, 3, and 4 respectively. All visits will be performed within a 4 week period.
Type 2 Diabetes Mellitus(DM)
ACTIVE COMPARATORPlacebo, oral glucose tolerance test, and subcutaneous administration of recombinant human IGF-1 will be given at visits 2, 3, and 4 respectively. All visits will be performed within a 4 week period.
Heathy Controls
ACTIVE COMPARATORPlacebo, oral glucose tolerance test, and subcutaneous administration of recombinant human IGF-1 will be given at visits 2, 3, and 4 respectively. All visits will be performed within a 4 week period.
Interventions
Participants will have their blood drawn for a baseline value and then will be asked to drink a beverage with 75 grams of sugar. Blood will then be drawn every 30 minutes for 2 hours.
Participants will receive a subcutaneous injection of recombinant human IGF-1 followed by a series of blood draws.
Participants will receive a subcutaneous injection of saline followed by a series of blood draws.
Eligibility Criteria
You may qualify if:
- Active acromegaly due to excess GH produced by a pituitary adenoma.
- Patients must have an elevated IGF-I compared to age and gender matched controls (as supplied by the laboratory) and fail to suppress GH to below 1 ng/ml after a standard 75g oral glucose tolerance test.
- Type 2 diabetes mellitus, defined by elevated fasting glucose ≥ 126 mg/dl (verified by two historical measurements), or plasma glucose ≥ 200 mg/dl two hours after a 75 g oral glucose load, or a random glucose ≥ 200 mg/dl.
You may not qualify if:
- Acromegaly Group
- Current medical therapy for acromegaly including dopamine agonists, somatostatin analogues, or growth hormone antagonists.
- For subjects on current therapy the following washout periods may be used:
- Cabergoline: 4 weeks
- Bromocriptine: 1 week
- Sandostatin LAR: 3 months
- Short-acting octreotide: 1 week
- Lanreotide: 3 months
- Pegvisomant: 4 weeks
- Subjects with a history of surgical therapy for treatment of acromegaly must have verification of active disease with verified elevated IGF-I for the subjects' age and gender compared to healthy controls (as supplied by the laboratory) (two measures) as well as a failure to suppress GH to below 1 ng/ml after OGTT.
- Current treatment for insulin resistance or type 2 DM including oral or injection medications.
- Fasting glucose ≥ 126 mg/dl at screening evaluation.
- Evidence of hepatic or renal disease defined as elevated transaminases, elevated serum creatinine.
- Pregnancy or breast feeding.
- Type 2 diabetes mellitus group
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Cedars-Sinai Medical Center Pituitary Center
Los Angeles, California, 90048, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Odelia Cooper
- Organization
- Cedars-Sinai Medical Center
Study Officials
- PRINCIPAL INVESTIGATOR
Odelia Cooper, MD
Cedars-Sinai Medical Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Purpose
- OTHER
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Staff Physician II
Study Record Dates
First Submitted
June 5, 2009
First Posted
June 8, 2009
Study Start
December 1, 2008
Primary Completion
August 1, 2013
Study Completion
June 1, 2014
Last Updated
July 9, 2019
Results First Posted
July 9, 2019
Record last verified: 2019-07