The Role of Phosphodiesterase Inhibitors in Incretin Secretion

Completed · Phase 1 · Has a placebo group

Conditions studied: Healthy Volunteers

In brief

Background: The drug Roflumilast (Daliresp) is used to treat Chronic Obstructive Pulmonary Disease (COPD). COPD is a lung disease that makes it difficult to breathe. Studies have shown that this drug decreased the blood sugar of people with type 2 diabetes. Sitagliptin (Januvia) is a medication presently used to treat diabetes. Researchers think that both of these drugs may decrease blood sugar by causing an increase in the hormone GLP-1.This hormone is secreted in the small intestines and stomach and is also known as an incretin. Researchers want to study how these drugs affect blood sugar, insulin, and other hormones in the blood. Objectives: * To study the effects of Roflumilast (Daliresp) and Sitagliptin (Januvia) on blood sugar and insulin. * To better understand GLP-1 and other gut hormones. This may lead to new treatments for type 2 diabetes. Eligibility: * Healthy volunteers age 21 55. * Body Mass Index (BMI) less than 30 Design: -This study will require one screening visit and four study visits, scheduled about 3-weeks apart. Screening visit requires participants to arrive after fasting for 10 hours and have the following: * Medical history, physical exam, height, weight, blood pressure measurements and blood and urine tests. * A 2-hour oral glucose tolerance test (OGTT). Participants will drink an orange-flavored drink containing 75 grams of sugar (300 calories). A blood sample will be taken prior to drinking the beverage and 2-hours later. * An electrocardiogram (EKG) to measure the electrical activity of the heart. * Questionnaires about risk for depression or suicide. Study visits 1to 4: * Participants will arrive the evening prior and blood work will be done to confirm eligibility. They will not eat or drink anything except water starting at 8:00 p.m. * About 6:30 a.m. the following day, an I.V. (small plastic tube) will be placed in an arm vein and used to take 20 blood samples over a period of about 11 hours. * Participants will receive one of the following study medication/placebo groupings in random order: 1. Roflumilast (Daliresp) 500 mcg pill; and 1 placebo pill 2. Sitaglipitin (Januvia) 100 mg pill; and 1 placebo pill 3. Roflumilast (Daliresp) 500 mcg pill; and Sitagliptin (Januvia) 100 mg pill 4. 2 placebo pills * One hour later, they will have a 10-hour mixed meal test (MMT). They will be asked to drink a nutritional shake (Ensure Plus). Blood samples will be taken over the next 10 hours to measure blood sugar, insulin and other hormones. At the end of the test, they will be given a meal. * Participants will answer questions about side effects and symptoms. They will receive a follow-up phone call within 10 days.

Key facts

Study ID

NCT02363335

Run by

National Institute on Aging (NIA)

People needed

29

Starts

2015-02-13

Expected to finish

2016-09-19

Last updated by the study team

2026-07-28

Who can join

Age: 21 and older, up to 55. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• FPG greater than or equal to 100 mg/dl or 2-hr OGTT greater than or equal to 140 mg/dL (evidence of glucose intolerance or diabetes)
• History of anemia, or Hemoglobin < 12.5 mg/dL for men and < 11.5 mg/dL for women during screening visit
• Weight < 110 pounds (due to blood volume requirement)
• Evidence of illicit drug use
• History of substance abuse including marijuana within the past 6 months
• History of smoking any tobacco products within six months prior to screening
• Alcohol intake > 30 grams (drink more than 2 beers per day OR equivalent amount of alcohol)
• History of Human Immunodeficiency Virus (HIV) infection
• History of active or chronic Hepatitis B and/or C infection
• History of psychiatric illnesses including major depressive disorder, schizophrenia, bipolar disorder
• Any lifetime history of suicide attempt
• History of any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) in the last year
• Any suicidal ideation of type 4 or 5 on the C-SSRS during any follow-up visits.
• Patient Health Questionnaire-9 (PHQ-9) score greater than or equal to 10 during screening visit or any follow-up study visits
• Generalized Anxiety Disorder-7 (GAD-7) score greater than or equal to 10 during screening visit or any follow-up visits
• History of pancreatitis
• History of liver or renal diseases
• History of gastrointestinal or endocrine disorders
• History of malignancy (unless P.I. determines that there is no impact of the prior malignancy on study outcomes, i.e. basal cell skin cancer)
• History of coronary disease or clinically significant abnormalities on electrocardiogram
• History of seizures or other neurologic diseases
• History of glucocorticoid use (over one month) or other immunosuppressive agents (any), i.e. Imuran, Neoral, Sandimmune, SangCya, basiliximab (Simulect), daclizumab (Zenapax), muromonab (Orthocolone OKT(3)) prednisone (Deltasone, Orasone) within the past six months
• Use of proton pump inhibitors (PPI s), i.e. Prilosec, Prevacid, Achiphex, Protonix, Nexium, Zegarid
• Women who are pregnant or nursing/breast-feeding a child
• Any medical history that, in the opinion of the investigator(s), may make participation of the subject in the study unsafe

Where it is running

• National Institute of Aging, Clinical Research Unit — Baltimore, Maryland, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.