The Effect of Dipeptidyl Peptidase 4 Inhibition on Growth Hormone Secretion in Women With Polycystic Ovarian Syndrome
Condition: Polycystic Ovary Syndrome
MeSH terms: Polycystic Ovary Syndrome; Syndrome
Intervention: Sitagliptin; Placebo
Intervention description: Sitagliptin 100 mg by mouth daily for 30 Days; 1 placebo pill by mouth per day for 30 days
Intervention MeSH terms: Sitagliptin Phosphate
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 23.0
Sex: Female
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: No
Keywords: Growth Hormone; Dipeptidyl Peptidase 4; Polycystic Ovary Syndrome

Summary:

      Adults with abdominal obesity are at high risk for cardiovascular disease and also exhibit
      diminished growth hormone (GH) secretion; the latter further contributes to the development
      of visceral adiposity, impaired fibrinolysis and inflammation.Growth hormone releasing
      hormone (GHRH), the primary stimulus for endogenous GH secretion, is a substrate of
      dipeptidyl peptidase 4 (DPP4); inhibition of DPP4 with the currently available anti-diabetic
      therapy, sitagliptin, may therefore increase GH secretion by decreasing the degradation of
      GHRH. The proposed research will test the hypothesis that chronic sitagliptin therapy will
      enhance GH secretion and vascular function while improving glucose tolerance in patients with
      impaired GH secretion who are at risk for the development of diabetes mellitus and
      cardiovascular disease, specifically obese women with polycystic ovary syndrome.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Females, age 18-40 years

          -  BMI ≥ 30 kg/m2

          -  Diagnosis of polycystic ovary syndrome defined by 2003 Rotterdam criteria as meeting
             two out of the three below criteria :

               -  Oligomenorrhea or amenorrhea

               -  clinical or biochemical evidence of hyperandrogenism (hirsutism and/or documented
                  upper normal or elevated serum testosterone in the absence of exogenous hormone
                  therapy or Metformin)

               -  documented history of polycystic ovaries on ultrasound examination

        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 150 mmHg and/or an untreated diastolic blood pressure (DBP) greater than 95 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 (Negative serum pregnancy test will be confirmed at
             screening visit and every study visit.)

          -  Surgical menopause, defined as s/p total hysterectomy including bilateral
             salpingo-oophorectomy

          -  Use of transdermal or oral contraceptive therapy. The use of these contraceptives must
             be discontinued at least 8 weeks prior to study initiation.

          -  The use of insulin sensitizers, specifically Metformin or thiazolidinediones must be
             discontinued 8 weeks prior to study initiation.

          -  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), prolactin, or morning 17 hydroxyprogesterone at
             the time of screening visit

          -  Impaired renal function, defined as estimated glomerular filtration rate (eGFR) <60

          -  Impaired hepatic function (AST or ALT > 2 X upper limit of normal range)

          -  Treatment with an investigational drug in the 1 month preceding the study

          -  Allergy to any of the medications used in this protocol

          -  Regular work of a night-shift or unusual schedule which may disrupt circadian rhythm.

          -  Personal or Family History (defined as first degree relative) of Pancreatic Cancer

          -  Personal history of Pancreatitis or known pancreatic lesions

          -  Coagulopathy as defined by history

          -  Regular NSAID use, including but not limited to, naproxen, ibuprofen, and aspirin

          -  Mental conditions rendering the subject unable to understand the nature, scope, and
             possible consequences of the study

          -  Inability to comply with the protocol, e.g., uncooperative attitude, inability to
             return for follow-up visits, and unlikelihood of completing the study

          -  Any underlying or acute disease requiring regular medication that could possibly pose
             a threat to the subject or make implementation of the protocol or interpretation of
             the study results difficult