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
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      Thirty-four obese (BMI ≥ 30 kg/m2) females (18-40 years old) with polycystic ovarian syndrome
      (PCOS) will participate in this randomized, double-blind, placebo-controlled crossover study.
      The use of oral contraceptives or metformin will be discontinued at least 30 days prior. In
      females experiencing monthly cycles, the outpatient visit will take place during the
      mid-luteal phase of the participant's menstrual cycle and the inpatient visit will take place
      during the late follicular phase.

      Subjects will be randomized to treatment order (sitagliptin 100 mg daily vs placebo) using a
      block randomization algorithm with a block size of two. The dose of sitagliptin was chosen as
      it is currently the FDA-recommended dose of sitagliptin for type 2 diabetic patients with
      unimpaired renal function. Subjects will receive standardized dietary counseling throughout
      the study; visits will be standardized to the menstrual cycle when possible. Subjects will
      take each therapy for one month; a minimum one month wash-out will separate study treatments.
      Side effects and compliance with study medication will be assessed at each visit in the
      clinical research center (CRC).

      Each subject will undergo one outpatient visit and one inpatient visit during each treatment.
      On each study day, subjects will report fasting to the CRC in the morning having abstained
      from exercise that morning. On each study day, subjects will receive an intravenous catheter.
      Subjects will undergo an oral glucose tolerance test (OGTT) during the outpatient study
      visit. During the inpatient study visit, endothelium-dependent and -independent vasodilation
      will be assessed using flow-mediated dilation technique with ultrasound. Standardized meals
      will be provided at lunch and dinner. Body composition will be determined in the afternoon.
      At 8 PM overnight frequent sampling for venous GH will begin every 10 minutes for 12 hours to
      determine overnight GH secretion.
    

Intervention name(s): Sitagliptin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Sitagliptin 100 mg by mouth daily for 30 Days; 1 placebo pill by mouth per day for 30 days
Other intervention name(s): Januvia
Intervention MeSH terms: Sitagliptin Phosphate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Growth Hormone; Dipeptidyl Peptidase 4; Polycystic Ovary Syndrome