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

NCT02122380 | Completed Phase 4 Results DMC

• 2 other identifiers: 131969K23HL119602-01A1
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Polycystic Ovary Syndrome

Keywords

Growth Hormone; Dipeptidyl Peptidase 4; Polycystic Ovary Syndrome

Outcome Measures

Primary Outcomes (1)

• Mean Overnight Growth Hormone Levels

  Growth hormone levels were determined every 10 minutes from 8 PM until 8 AM during the inpatient visit on the last day of each treatment. A mean of the GH levels was calculated for each participant, and then the value from each participant was averaged across all participants.

  At completion of 30 days of placebo treatment and at completion of 30 days of sitagliptin treatment; every 10 minutes from 8 PM until 8 AM.

Secondary Outcomes (4)

• Early Insulin Secretion During Oral Glucose Tolerance Test

  During Outpatient Visit (after 2 weeks of therapy) during placebo and sitagliptin treatment periods. Insulin levels were obtained at time 0, 15 and 30 minutes following 75 gram glucose ingestion.

• Area Under the Curve (AUC) for Blood Glucoses During 75 Gram Oral Glucose Tolerance Test

  During Outpatient Visit (after 2 weeks of therapy) during placebo and sitagliptin treatment periods. Every 15 minutes from time 0 to 120 minutes after oral glucose ingestion.

• Visceral Adipose Tissue

  At completion of 30 days of placebo treatment and at completion of 30 days of sitagliptin treatment.

• Vascular Function (Endothelium-dependent Vasodilation)

  Vascular function was determined by measuring brachial artery diameter at rest and during reactive hyperemia and calculating percent change. This was determined after 30 days of placebo treatment and after 30 days of sitagliptin treatment.

Study Arms (2)

Sitagliptin, then Placebo

EXPERIMENTAL

Sitagliptin 100 mg by mouth daily for 30 days followed by Placebo daily for 30 days

Drug: Sitagliptin; Drug: Placebo

Placebo, then Sitagliptin

EXPERIMENTAL

Placebo daily for 30 days followed by Sitagliptin 100 mg daily for 30 days

Drug: Sitagliptin; Drug: Placebo

Interventions

Sitagliptin DRUG

Sitagliptin 100 mg by mouth daily for 30 Days

Also known as: Januvia

Placebo, then Sitagliptin; Sitagliptin, then Placebo

Placebo DRUG

1 placebo pill by mouth per day for 30 days

Placebo, then Sitagliptin; Sitagliptin, then Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• Devin JK, Nian H, Celedonio JE, Wright P, Brown NJ. Sitagliptin Decreases Visceral Fat and Blood Glucose in Women With Polycystic Ovarian Syndrome. J Clin Endocrinol Metab. 2020 Jan 1;105(1):136-51. doi: 10.1210/clinem/dgz028.

  PMID: 31529097 DERIVED

MeSH Terms

Conditions

Polycystic Ovary Syndrome

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Results Point of Contact

• Title: Dr. Jessica Devin
• Organization: Vanderbilt University Medical Center

jessica.devin@vumc.org

970-875-2708

Study Officials

• Jessica Devin, MD MSCI

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 14, 2014
• First Posted: April 24, 2014
• Study Start: February 1, 2016
• Primary Completion: August 1, 2019
• Study Completion: August 1, 2019
• Last Updated: May 8, 2020
• Results First Posted: May 8, 2020

Record last verified: 2020-04

Locations

US (1)