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N/A N=28 Single-blind Other

Growth Hormone Feedback to Insulin-like Growth Factor-I (IGF-1) and Oral Glucose Tolerance Test (OGTT)

Acromegaly · Type 2 Diabetes Mellitus

Enrolled (actual)
28
Serious AEs
0.0%
Results posted
Jul 2019
Primary outcome: Primary: Percentage With Growth Hormone (GH) Suppression to < 0.4 ng/ml — 0; 7; 8 Participants

Study Design & Population

Study type
Interventional
Phase
N/A
Interventions
Oral Glucose Tolerance Test (Diagnostic_test); Subcutaneous administration of recombinant human IGF-1 (Diagnostic_test); Placebo (Diagnostic_test)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Cedars-Sinai Medical Center
Primary completion
Aug 2013

Outcome Measures

OutcomeResultp-value
PRIMARY
Percentage With Growth Hormone (GH) Suppression to < 0.4 ng/ml
0; 7; 8
SECONDARY
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
10927; 5079; 9105; 5603; 2538; 4266
SECONDARY
Median Insulin Level in Response to Placebo, OGTT, and rhIGF1 Testing
7; 9; 4; 55; 39.5; 41.5
SECONDARY
Median Bioactive IGF-1 Area Under the Curve in Response to Placebo, OGTT, and rhIGF1 Testing
716; 291; 302; 699; 270; 339

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.

Eligibility Criteria

Inclusion Criteria

  • 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.

Exclusion Criteria

  • 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
  • Patients taking non-insulin medications for diabetes treatment will be excluded.
  • Diagnosis of acromegaly.
  • Evidence of hepatic or renal disease defined as elevated transaminases, elevated serum creatinine.
  • Pregnancy or breast feeding.
  • Healthy Control Group
  • History of diabetes mellitus or impaired glucose tolerance, history of acromegaly.
  • 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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00915954). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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