Effect of DPP4 Inhibition on Growth Hormone Secretion
Condition: Obesity
MeSH terms: Obesity
Intervention: Sitagliptin; Pegvisomant; Placebo; L-NMMA; Exendin 9-39
Intervention description: During Aim 1, given on one of two study days (other study day subjects receive placebo.) During Aim 2, given during both of two study days.; During Aim 2, given 72 hours prior to one of two study days (Group B subjects only); During Aim 1, given on one of two study days (other study day subjects receive sitagliptin.) During Aim 2, given on one of two study days (other study day subjects receive either L-NMMA, pegvisomant, or Exendin 9-39 pending their group assignment); During Aim 2, given during one of two study days (Group A subjects only); During Aim 2, given during one of two study days (Group C subjects only)
Intervention MeSH terms: Sitagliptin Phosphate
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: obesity; growth hormone

Summary:

      This study tests the following hypotheses:

      Aim 1: Test the hypothesis that acute dipeptidyl peptidase 4 (DPP4) inhibition with the
      currently available anti-diabetic drug, sitagliptin, will increase stimulated growth hormone
      (GH) secretion in healthy lean adults by decreasing the degradation of growth hormone
      releasing hormone (GHRH).

      Aim 2: Test the hypothesis that decreased degradation of GHRH during acute DPP4 inhibition
      will result in an increase in endothelium-dependent vasodilation mediated by GH and
      independent from GLP1 (glucagon like peptide-1) in healthy lean adults.

      This study promises to provide novel data regarding how this increasingly used class of
      anti-diabetic drugs affects the pituitary GH axis and could affect blood vessel relaxation.
      Growth hormone levels are low in the setting of obesity and pre-diabetes. A further study may
      evaluate the effect of chronic DPP4 inhibitor therapy in a population of patients with
      obesity and pre-diabetes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 18 to 40 years inclusive

          -  BMI ≤ 25 kg/m2

          -  For female subjects:

        Status-post surgical sterilization, or If of child-bearing potential, utilization of a
        barrier method of birth control following negative serum pregnancy test at screening visit
        and on every study day

        Exclusion Criteria:

          -  Smoking

          -  Type 1 or Type 2 Diabetes Mellitus, as defined by a fasting glucose of 126 mg/dL or
             greater at the time of screening visit or the use of anti-diabetic medication

          -  Hypertension, as defined by an untreated seated systolic blood pressure (SBP) greater
             than 140 mmHg and/or an untreated diastolic blood pressure (DBP) greater than 90 mmHg
             at the time of screening visit or the use of anti-hypertensive medication

          -  History of reported or recorded hypoglycemia (plasma glucose < 70 mg/dL)

          -  Pregnancy and/or Breast-Feeding

          -  Use of any medication other than multivitamin, including use of transdermal as well as
             oral hormone replacement therapy or use of oral contraceptive therapy

          -  Anemia defined as hematocrit <35% at screening visit

          -  Cardiovascular or cerebrovascular disease, including history of myocardial infarction,
             history of congestive heart failure, history of stroke

          -  Pulmonary Hypertension

          -  Abnormal thyroid hormone levels (TSH) at the time of screening visit

          -  Abnormal serum insulin like growth factor-1 (IGF-1) at the time of screening visit

          -  Impaired renal function, defined as estimated glomerular filtration rate (eGFR) <60
             mL/min/1.73 m^2

          -  Impaired hepatic function (alanine or aspartate transaminase > 2 X upper limit of
             normal range)

          -  Treatment with an investigational drug in the 1 month preceding the study