The Effect of Dipeptidyl Peptidase 4 Inhibition on Growth Hormone Secretion in Women With Polycystic Ovarian Syndrome

• Status: Completed
• Trial end date: 2019-08-01
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vanderbilt University
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Hormones; Sitagliptin Phosphate

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